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Sample records for chikungunya viruses imported

  1. Chikungunya virus

    Science.gov (United States)

    Chikungunya virus infection; Chikungunya ... Where Chikungunya is found Before 2013, the virus was found in Africa, Asia, Europe, and the Indian and Pacific oceans. In late 2013, outbreaks occurred for the first time in the ...

  2. Chikungunya Virus

    Science.gov (United States)

    ... Gaines, PhD, MPH, MA, CHES Differentiating Chikungunya From Dengue: A Clinical Challenge For Travelers CDC Travelers' Health Chikungunya Virus Home Prevention Transmission Symptoms & Treatment Geographic Distribution Chikungunya virus in ...

  3. Genetic analysis of chikungunya viruses imported to mainland China in 2008

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    Li Xiaobo

    2010-01-01

    Full Text Available Abstract Background Chikungunya virus (CHIKV has caused large outbreaks worldwide in recent years, especially on the islands of the Indian Ocean and India. The virus is transmitted by mosquitoes (Aedes aegypti, which are widespread in China, with an especially high population density in southern China. Analyses of full-length viral sequences revealed the acquisition of a single adaptive mutation providing a selective advantage for the transmission of CHIKV by this species. No outbreaks due to the local transmission of CHIKV have been reported in China, and no cases of importation were detected on mainland China before 2008. We followed the spread of imported CHIKV in southern China and analyzed the genetic character of the detected viruses to evaluate their potential for evolution. Results The importation of CHIKV to mainland China was first detected in 2008. The genomic sequences of four of the imported viruses were identified, and phylogenetic analysis demonstrated that the sequences were clustered in the Indian Ocean group; however, seven amino acid changes were detected in the nonstructural protein-coding region, and five amino acid changes were noted in the structural protein-coding regions. In particular, a novel substitution in E2 was detected (K252Q, which may impact the neurovirulence of CHIKV. The adaptive mutation A226V in E1 was observed in two imported cases of chikungunya disease. Conclusions Laboratory-confirmed CHIKV infections among travelers visiting China in 2008 were presented, new mutations in the viral nucleic acids and proteins may represent adaptive mutations for human or mosquito hosts.

  4. Tenosinovitis por virus Chikungunya

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    Alfredo Seijo

    2014-12-01

    Full Text Available Se presenta a la consulta un hombre proveniente de la República Dominicana con una tenosinovitis del extensor del dedo medio derecho; en la convalecencia inmediata, segunda curva febril luego de 48 horas de permanecer asintomático de una enfermedad febril aguda, y marcada astenia, exantema pruriginoso, poliartralgias con impotencia funcional y rigidez articular generalizada. Los exámenes bioquímicos no aportaron datos de interés para el diagnóstico. La serología para virus dengue fue negativa. La detección de IgM y de anticuerpos neutralizantes para virus Chikungunya (CHIKV fueron positivos.

  5. A REVIEW ON CHIKUNGUNYA VIRUS

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    Vimal Kumar Birendra

    2012-02-01

    Full Text Available Mosquitoes transmit numerous arboviruses including dengue and chikungunya virus (CHIKV. Chikungunya is a re-emerging arthropod-borne viral disease caused by Chikungunya virus (CHIKV belonging to the Togaviridae family of genus Alphavirus. It is a virus with a single stranded, positive sense RNA, as its genome. It is maintained in a sylvatic and urban cycle involving humans and the mosquito species Aedes aegypti and Aedes albopictus. It has a major health impact on humans as it causes fever, rashes, arthralgia and myalgia. Polyarthralgia is the most important feature of CHIKV infection which primarily affects the small joints of the wrists and fingers along with the large joints like shoulders and knees. Currently, there are no vaccines or treatment regimens available for CHIKV infection. The molecular mechanism underlying the chronic polyarthralgia observed in patients is not well understood. The abundance of bacteria from the Enterobacteriaceae family increased with CHIKV infection whereas the abundance of known insect endosymbionts like Wolbachia and Blattabacterium decreased. In this review we have summarized the CHIKV organization, replication, epidemiology, clinical manifestations and pathogenesis with emphasis on the arthralgia.

  6. Complete Genome Sequences of Chikungunya Virus Strains Isolated in Mexico: First Detection of Imported and Autochthonous Cases

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    Ortiz-Alcántara, Joanna; Fragoso-Fonseca, David Esaú; Garcés-Ayala, Fabiola; Escobar-Escamilla, Noé; Vázquez-Pichardo, Mauricio; Núñez-León, Alma; Torres-Rodríguez, María de la Luz; Torres-Longoria, Belem; López-Martínez, Irma; Ruíz-Matus, Cuitláhuac; Kuri-Morales, Pablo; Ramírez-González, José Ernesto

    2015-01-01

    The mosquito-borne chikungunya virus, an alphavirus of the Togaviridae family, is responsible for acute polyarthralgia epidemics. Here, we report the complete genome sequences of two chikungunya virus strains, InDRE04 and InDRE51, identified in the Mexican states of Jalisco and Chiapas in 2014. Phylogenetic analysis showed that both strains belong to the Asian genotype. PMID:25953170

  7. Chikungunya Virus: What You Need to Know

    Science.gov (United States)

    Chikungunya Virus: What you need to know Chikungunya (pronunciation: \\chik-en-gun-ye) is: A virus spread through Aedes species mosquito bites. Aedes mosquitoes also spread dengue and Zika viruses. A risk to anyone traveling to a region ...

  8. First Imported Case of Chikungunya Virus Infection in a Travelling Canadian Returning from the Caribbean

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    Christian Therrien

    2016-01-01

    Full Text Available This is the first Canadian case of Chikungunya virus (CHIKV infection reported in a traveller returning from the Caribbean. Following multiple mosquito bites in Martinique Island in January 2014, the patient presented with high fever, headaches, arthralgia on both hands and feet, and a rash on the trunk upon his return to Canada. Initial serological testing for dengue virus infection was negative. Support therapy with nonsteroidal anti-inflammatory drugs was administered. The symptoms gradually improved 4 weeks after onset with residual arthralgia and morning joint stiffness. This clinical feature prompted the clinician to request CHIKV virus serology which was found to be positive for the presence of IgM and neutralizing antibodies. In 2014, over four hundred confirmed CHIKV infection cases were diagnosed in Canadian travellers returning from the Caribbean and Central America. Clinical suspicion of CHIKV or dengue virus infections should be considered in febrile patients with arthralgia returning from the recently CHIKV endemic countries of the Americas.

  9. Chikungunya

    Science.gov (United States)

    ... through infected blood. There have been outbreaks of chikungunya virus in Africa, Asia, Europe, the Indian and Pacific ... A blood test can show whether you have chikungunya virus. There are no vaccines or medicines to treat ...

  10. Help Control Mosquitoes that Spread Dengue, Chikungunya, and Zika Viruses

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    Help Control Mosquitoes that Spread Dengue, Chikungunya, and Zika Viruses B Z Z Z Z . Aside from being ... or Aedes albopictus ) can spread dengue, chikungunya, or Zika viruses. People become infected with dengue, chikungunya, or Zika ...

  11. Antiviral Perspectives for Chikungunya Virus

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    Deepti Parashar

    2014-01-01

    Full Text Available Chikungunya virus (CHIKV is a mosquito-borne pathogen that has a major health impact in humans and causes acute febrile illness in humans accompanied by joint pains and, in many cases, persistent arthralgia lasting for weeks to years. CHIKV reemerged in 2005-2006 in several parts of the Indian Ocean islands and India after a gap of 32 years, causing millions of cases. The re-emergence of CHIKV has also resulted in numerous outbreaks in several countries in the eastern hemisphere, with a threat to further expand in the near future. However, there is no vaccine against CHIKV infection licensed for human use, and therapy for CHIKV infection is still mainly limited to supportive care as antiviral agents are yet in different stages of testing or development. In this review we explore the different perspectives for chikungunya treatment and the effectiveness of these treatment regimens and discuss the scope for future directions.

  12. Chikungunya virus: emerging targets and new opportunities for medicinal chemistry.

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    Rashad, Adel A; Mahalingam, Suresh; Keller, Paul A

    2014-02-27

    Chikungunya virus is an emerging arbovirus that is widespread in tropical regions and is spreading quickly to temperate climates with recent epidemics in Africa and Asia and documented outbreaks in Europe and the Americas. It is having an increasingly major impact on humankind, with potentially life-threatening and debilitating arthritis. There is no treatment available, and only in the past 24 months have lead compounds for development as potential therapeutics been reported. This Perspective discusses the chikungunya virus as a significant, new emerging topic for medicinal chemistry, highlighting the key viral target proteins and their molecular functions that can be used in drug design, as well as the most important ongoing developments for anti-chikungunya virus research. It represents a complete picture of the current medicinal chemistry of chikungunya, supporting the development of chemotherapeutics through drug discovery and design targeting this virus.

  13. Antiviral Strategies Against Chikungunya Virus.

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    Abdelnabi, Rana; Neyts, Johan; Delang, Leen

    2016-01-01

    In the last few decades the Chikungunya virus (CHIKV) has evolved from a geographically isolated pathogen to a virus that is widespread in many parts of Africa, Asia and recently also in Central- and South-America. Although CHIKV infections are rarely fatal, the disease can evolve into a chronic stage, which is characterized by persisting polyarthralgia and joint stiffness. This chronic CHIKV infection can severely incapacitate patients for weeks up to several years after the initial infection. Despite the burden of CHIKV infections, no vaccine or antivirals are available yet. The current therapy is therefore only symptomatic and consists of the administration of analgesics, antipyretics, and anti-inflammatory agents. Recently several molecules with various viral or host targets have been identified as CHIKV inhibitors. In this chapter, we summarize the current status of the development of antiviral strategies against CHIKV infections. PMID:27233277

  14. Characterization of reemerging chikungunya virus.

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    Marion Sourisseau

    2007-06-01

    Full Text Available An unprecedented epidemic of chikungunya virus (CHIKV infection recently started in countries of the Indian Ocean area, causing an acute and painful syndrome with strong fever, asthenia, skin rash, polyarthritis, and lethal cases of encephalitis. The basis for chikungunya disease and the tropism of CHIKV remain unknown. Here, we describe the replication characteristics of recent clinical CHIKV strains. Human epithelial and endothelial cells, primary fibroblasts and, to a lesser extent, monocyte-derived macrophages, were susceptible to infection and allowed viral production. In contrast, CHIKV did not replicate in lymphoid and monocytoid cell lines, primary lymphocytes and monocytes, or monocyte-derived dendritic cells. CHIKV replication was cytopathic and associated with an induction of apoptosis in infected cells. Chloroquine, bafilomycin-A1, and short hairpin RNAs against dynamin-2 inhibited viral production, indicating that viral entry occurs through pH-dependent endocytosis. CHIKV was highly sensitive to the antiviral activity of type I and II interferons. These results provide a general insight into the interaction between CHIKV and its mammalian host.

  15. Characterization of Reemerging Chikungunya Virus

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    Sourisseau, Marion; Schilte, Clémentine; Casartelli, Nicoletta; Trouillet, Céline; Guivel-Benhassine, Florence; Rudnicka, Dominika; Sol-Foulon, Nathalie; Roux, Karin Le; Prevost, Marie-Christine; Fsihi, Hafida; Frenkiel, Marie-Pascale; Blanchet, Fabien; Afonso, Philippe V; Ceccaldi, Pierre-Emmanuel; Ozden, Simona; Gessain, Antoine; Schuffenecker, Isabelle; Verhasselt, Bruno; Zamborlini, Alessia; Saïb, Ali; Rey, Felix A; Arenzana-Seisdedos, Fernando; Desprès, Philippe; Michault, Alain; Albert, Matthew L; Schwartz, Olivier

    2007-01-01

    An unprecedented epidemic of chikungunya virus (CHIKV) infection recently started in countries of the Indian Ocean area, causing an acute and painful syndrome with strong fever, asthenia, skin rash, polyarthritis, and lethal cases of encephalitis. The basis for chikungunya disease and the tropism of CHIKV remain unknown. Here, we describe the replication characteristics of recent clinical CHIKV strains. Human epithelial and endothelial cells, primary fibroblasts and, to a lesser extent, monocyte-derived macrophages, were susceptible to infection and allowed viral production. In contrast, CHIKV did not replicate in lymphoid and monocytoid cell lines, primary lymphocytes and monocytes, or monocyte-derived dendritic cells. CHIKV replication was cytopathic and associated with an induction of apoptosis in infected cells. Chloroquine, bafilomycin-A1, and short hairpin RNAs against dynamin-2 inhibited viral production, indicating that viral entry occurs through pH-dependent endocytosis. CHIKV was highly sensitive to the antiviral activity of type I and II interferons. These results provide a general insight into the interaction between CHIKV and its mammalian host. PMID:17604450

  16. Diagnostic Options and Challenges for Dengue and Chikungunya Viruses

    OpenAIRE

    Mardekian, Stacey K.; Roberts, Amity L.

    2015-01-01

    Dengue virus (DENV) and Chikungunya virus (CHIKV) are arboviruses that share the same Aedes mosquito vectors and thus overlap in their endemic areas. These two viruses also cause similar clinical presentations, especially in the initial stages of infection, with neither virus possessing any specific distinguishing clinical features. Because the outcomes and management strategies for these two viruses are vastly different, early and accurate diagnosis is imperative. Diagnosis is also important...

  17. Chikungunya virus iridocyclitis in Fuchs′ heterochromic iridocyclitis

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    Mahendradas Padmamalini

    2010-01-01

    Full Text Available We are reporting a case of bilateral Fuchs′ heterochromic iridocyclitis with chikungunya virus infection in the left eye. A 20-year-old female was presented with a past history of fever suggestive of chikungunya with bilateral Fuchs′ heterochromic iridocyclitis and complicated cataract. She had a tripod dendritic pattern of keratic precipitates by confocal microscopy in the left eye with a stippled pattern of keratic precipitates in both eyes. The real-time polymerase chain reaction (RT-PCR assay in the aqueous humor detected 98 copies/ml of chikungunya virus RNA. The patient underwent clear corneal phacoemulsification with in-the-bag intraocular lens implantation in the left eye with a good visual outcome. This is the first report where the presence of chikungunya virus RNA has been associated with a case of bilateral Fuchs′ heterochromic iridocyclitis.

  18. Detection of chikungunya virus antigen by a novel rapid immunochromatographic test.

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    Okabayashi, Tamaki; Sasaki, Tadahiro; Masrinoul, Promsin; Chantawat, Nantarat; Yoksan, Sutee; Nitatpattana, Narong; Chusri, Sarunyou; Morales Vargas, Ronald E; Grandadam, Marc; Brey, Paul T; Soegijanto, Soegeng; Mulyantno, Kris Cahyo; Churrotin, Siti; Kotaki, Tomohiro; Faye, Oumar; Faye, Ousmane; Sow, Abdourahmane; Sall, Amadou Alpha; Puiprom, Orapim; Chaichana, Panjaporn; Kurosu, Takeshi; Kato, Seiji; Kosaka, Mieko; Ramasoota, Pongrama; Ikuta, Kazuyoshi

    2015-02-01

    Chikungunya fever is a mosquito-borne disease of key public health importance in tropical and subtropical countries. Although severe joint pain is the most distinguishing feature of chikungunya fever, diagnosis remains difficult because the symptoms of chikungunya fever are shared by many pathogens, including dengue fever. The present study aimed to develop a new immunochromatographic diagnosis test for the detection of chikungunya virus antigen in serum. Mice were immunized with isolates from patients with Thai chikungunya fever, East/Central/South African genotype, to produce mouse monoclonal antibodies against chikungunya virus. Using these monoclonal antibodies, a new diagnostic test was developed and evaluated for the detection of chikungunya virus. The newly developed diagnostic test reacted with not only the East/Central/South African genotype but also with the Asian and West African genotypes of chikungunya virus. Testing of sera from patients suspected to have chikungunya fever in Thailand (n = 50), Laos (n = 54), Indonesia (n = 2), and Senegal (n = 6) revealed sensitivity, specificity, and real-time PCR (RT-PCR) agreement values of 89.4%, 94.4%, and 91.1%, respectively. In our study using serial samples, a new diagnostic test showed high agreement with the RT-PCR within the first 5 days after onset. A rapid diagnostic test was developed using mouse monoclonal antibodies that react with chikungunya virus envelope proteins. The diagnostic accuracy of our test is clinically acceptable for chikungunya fever in the acute phase.

  19. Nowcast Predictions for Local Transmission of Chikungunya Virus

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    U.S. Department of Health & Human Services — Interactive visualization: http://www.cdc.gov/chikungunya/modeling/index.html. This dataset contains monthly predictions for the spread of chikungunya virus...

  20. Nowcast Predictions for Chikungunya Virus-Infected Travelers

    Data.gov (United States)

    U.S. Department of Health & Human Services — Interactive visualization: http://www.cdc.gov/chikungunya/modeling/index.html. This dataset contains monthly predictions for the spread of chikungunya virus...

  1. Interspecies transmission and chikungunya virus emergence.

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    Tsetsarkin, Konstantin A; Chen, Rubing; Weaver, Scott C

    2016-02-01

    Chikungunya virus (CHIKV) causes severe, debilitating, often chronic arthralgia with high attack rates, resulting in severe morbidity and economic costs to affected communities. Since its first well-documented emergence in Asia in the 1950s, CHIKV has infected millions and, since 2007, has spread widely, probably via viremic travelers, to initiate urban transmission in Europe, the South Pacific, and the Americas. Some spread has been facilitated by adaptive envelope glycoprotein substitutions that enhance transmission by the new vector, Aedes albopictus. Although epistatic constraints may prevent the impact of these mutations in Asian strains now circulating in the Americas, as well as in African CHIKV strains imported into Brazil last year, these constraints could eventually be overcome over time to increase the transmission by A. albopictus in rural and temperate regions. Another major determinant of CHIKV endemic stability in the Americas will be its ability to spill back into an enzootic cycle involving sylvatic vectors and nonhuman primates, an opportunity exploited by yellow fever virus but apparently not by dengue viruses. PMID:26986235

  2. Activity of andrographolide against chikungunya virus infection

    OpenAIRE

    Phitchayapak Wintachai; Parveen Kaur; Regina Ching Hua Lee; Suwipa Ramphan; Atichat Kuadkitkan; Nitwara Wikan; Sukathida Ubol; Sittiruk Roytrakul; Justin Jang Hann Chu; Smith, Duncan R.

    2015-01-01

    Chikungunya virus (CHIKV) is a re-emerging mosquito-borne alphavirus that has recently engendered large epidemics around the world. There is no specific antiviral for treatment of patients infected with CHIKV, and development of compounds with significant anti-CHIKV activity that can be further developed to a practical therapy is urgently required. Andrographolide is derived from Andrographis paniculata, a herb traditionally used to treat a number of conditions including infections. This stud...

  3. A fatal case of chikungunya virus infection with liver involvement.

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    Chua, H H; Abdul Rashid, K; Law, W C; Hamizah, A; Chem, Y K; Khairul, A H; Chua, K B

    2010-03-01

    Recovery from chikungunya is previously considered universal and mortality due to the virus is rare and unusual. Findings from recent chikungunya outbreaks occurred in Reunion Island and India have since challenged the conventional view on the benign nature of the illness. Malaysia has experienced at least of 4 outbreaks of chikungunya since 1998. In the present on-going large outbreak due to chikungunya virus of Central/East African genotype, a previous healthy sixty six years gentleman without co-morbidity was noted to have severe systemic infection by the virus and involvement of his liver. He subsequently passed away due to cardiovascular collapse after 5 days of illness.

  4. Chikungunya Virus Growth and Fluorescent Labeling: Detection of Chikungunya Virus by Immunofluorescence Assay.

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    Moi, Meng Ling; Takasaki, Tomohiko

    2016-01-01

    Immunofluorescence assay (IFA) is a highly versatile and sensitive assay for detection and titration of chikungunya virus (CHIKV). The IFA technique requires virus-infected cells (viral antigen) and antibodies specific to the viral antigens for detection. Suitable antibodies for detection include monoclonal antibodies specific to CHIKV structural and nonstructural proteins, polyclonal antibodies, and convalescent serum samples. Here, the details of virus antigen preparation, detection by IFA method, and applications are described. The described IFA method is potentially useful in a wide range of studies including virus growth kinetics and virus infection mechanism studies. Additionally, the described IFA method can be modified for applications in arbovirus diagnosis, including CHIKV.

  5. Characterization of chikungunya virus-like particles.

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    Nitchakarn Noranate

    Full Text Available Chikungunya virus (CHIKV is becoming a global concern due to the increasing number of outbreaks throughout the world and the absence of any CHIKV-specific vaccine or treatment. Virus-like particles (VLPs are multistructured proteins that mimic the organization and conformation of native viruses but lack the viral genome. They are noninfectious and potentially safer vaccine candidates. Recent studies demonstrated that the yield of CHIKV VLPs varies depending on the strains, despite the 95% amino acid similarity of the strains. This might be due to the codon usage, since protein expression is differently controlled by different organisms. We optimized the region encoding CHIKV structural proteins, C-E3-E2-6k-E1, inserted it into a mammalian expression vector, and used the resulting construct to transfect 293 cells. We detected 50-kDa proteins corresponding to E1 and/or E2 in the cell lysate and the supernatant. Transmission electron microscopy revealed spherical particles with a 50- to 60-nm diameter in the supernatant that resembled the native CHIKV virions. The buoyant density of the VLPs was 1.23 g/mL, and the yield was 20 µg purified VLPs per 108 cells. The VLPs aggregated when mixed with convalescent sera from chikungunya patients, indicating that their antigenicity is similar to that of native CHIKV. Antibodies elicited with the VLPs were capable of detecting native CHIKV, demonstrating that the VLPs retain immunogenicity similar to that of the native virion. These results indicated that CHIKV VLPs are morphologically, antigenically, and immunologically similar to the native CHIKV, suggesting that they have potential for use in chikungunya vaccines.

  6. Diagnostic Options and Challenges for Dengue and Chikungunya Viruses

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    Stacey K. Mardekian

    2015-01-01

    Full Text Available Dengue virus (DENV and Chikungunya virus (CHIKV are arboviruses that share the same Aedes mosquito vectors and thus overlap in their endemic areas. These two viruses also cause similar clinical presentations, especially in the initial stages of infection, with neither virus possessing any specific distinguishing clinical features. Because the outcomes and management strategies for these two viruses are vastly different, early and accurate diagnosis is imperative. Diagnosis is also important for surveillance, outbreak control, and research related to vaccine and drug development. Available diagnostic tests are aimed at detection of the virus, its antigenic components, or the host immune antibody response. In this review, we describe the recent progress and continued challenges related to the diagnosis of DENV and CHIKV infections.

  7. How great is the threat of chikungunya virus?

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    Waggoner, Jesse J; Pinsky, Benjamin A

    2015-03-01

    In the last decade, chikungunya virus has emerged from an obscure arbovirus that caused limited outbreaks of disease in Africa and Asia to the cause of a pandemic affecting millions of people and spanning five continents. Two separate chikungunya virus genotypes have been responsible for outbreaks during this period, including strains adapted to transmission in Aedes albopictus mosquitoes. Further spread of this virus into new regions of the Western Hemisphere is predicted during the present rainy season in the tropics, and recurrent viral introductions and disease outbreaks, as occurred in Réunion in 2010, should be expected. Chikungunya virus no longer simply threatens; it has arrived as a significant, global pathogen.

  8. A Case of Chikungunya Virus Induced Arthralgia Responsive to Colchicine.

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    Redel, Henry

    2016-04-01

    Chikungunya virus is an emerging infectious disease that has started circulating throughout the Americas and Caribbean. It can lead to persistent arthralgia lasting months to years. Treatment has been symptomatic with nonsteroidal anti-inflammatory medications. This case report describes a trial of colchicine for chikungunya arthralgia in 1 patient. PMID:27419183

  9. Proteomics profiling of chikungunya-infected Aedes albopictus C6/36 cells reveal important mosquito cell factors in virus replication.

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    Regina Ching Hua Lee

    2015-03-01

    Full Text Available Chikungunya virus (CHIKV is the only causative agent of CHIKV fever with persistent arthralgia, and in some cases may lead to neurological complications which can be highly fatal, therefore it poses severe health issues in many parts of the world. CHIKV transmission can be mediated via the Aedes albopictus mosquito; however, very little is currently known about the involvement of mosquito cellular factors during CHIKV-infection within the mosquito cells. Unravelling the neglected aspects of mosquito proteome changes in CHIKV-infected mosquito cells may increase our understanding on the differences in the host factors between arthropod and mammalian cells for successful replication of CHIKV. In this study, the CHIKV-infected C6/36 cells with differential cellular proteins expression were profiled using two-dimensional gel electrophoresis (2DE coupled with the use of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS. 2DE analysis on CHIKV-infected C6/36 cells has shown 23 mosquito cellular proteins that are differentially regulated, and which are involved diverse biological pathways, such as protein folding and metabolic processes. Among those identified mosquito proteins, spermatogenesis-associated factor, enolase phosphatase e-1 and chaperonin-60kD have been found to regulate CHIKV infection. Furthermore, siRNA-mediated gene knockdown of these proteins has demonstrated the biological importance of these host proteins that mediate CHIKV infection. These findings have provided an insight to the importance of mosquito host factors in the replication of CHIKV, thus providing a potential channel for developing novel antiviral strategies against CHIKV transmission.

  10. Chikungunya virus, epidemiology, clinics and phylogenesis:A review

    Institute of Scientific and Technical Information of China (English)

    Alessandra Lo Presti; Alessia Lai; Eleonora Cella; Gianguglielmo Zehender; Massimo Ciccozzi

    2014-01-01

    Chikungunya virus is a mosquito-transmitted alphavirus that causes chikungunya fever, a febrile illness associated with severe arthralgia and rash.Chikungunya virus is transmitted by culicine mosquitoes;Chikungunya virus replicates in the skin, disseminates to liver, muscle, joints, lymphoid tissue and brain, presumably through the blood.Phylogenetic studies showed that the IndianOcean and theIndian subcontinent epidemics were caused by two different introductions of distinct strains ofEast/Central/SouthAfrican genotype ofCHIKV.The paraphyletic grouping ofAfricanCHIK viruses supports the historical evidence that the virus was introduced into Asia fromAfrica.Phylogenetic analysis dividedChikungunya virus isolates into three distinct genotypes based on geographical origins: thefirst, theWestAfrica genotype, consisted of isolates fromSenegal andNigeria; the second contained strains fromEast/Central/SouthAfrican genotype, while the third contained solelyAsian.The most recent common ancestor for the recent epidemic, which ravagedIndianOcean islands andIndian subcontinent in2004–2007, was found to date in2002.Asian lineage dated about1952 and exhibits similarspread patterns of the recentIndian Ocean outbreak lineage, with successive epidemics detected along an eastward path.Asian group splitted into two clades: anIndian lineage and a south east lineage.Outbreaks ofChikungunya virus fever inAsia have not been associated necessarily with outbreaks inAfrica.Phylogenetic tools can reconstruct geographic spread ofChikungunya virus during the epidemics wave.The good management of patients with acuteChikungunya virus infection is essential for public health in susceptible areas with currentAedes spp activity.

  11. Temperature Tolerance and Inactivation of Chikungunya Virus.

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    Huang, Yan-Jang S; Hsu, Wei-Wen; Higgs, Stephen; Vanlandingham, Dana L

    2015-11-01

    In late 2013, chikungunya virus (CHIKV) was introduced to the New World and large outbreaks occurred in the Caribbean islands causing over a million suspected and over 20,000 laboratory-confirmed cases. Serological analysis is an essential component for the diagnosis of CHIKV infection together with virus isolation and detection of viral nucleic acid. Demonstrating virus neutralizing by serum antibodies in a plaque reduction neutralization test (PRNT) is the gold standard of all serological diagnostic assays. Prior to the testing, heat inactivation of serum at 56°C for 30 min is required for the inactivation of complement activity and adventitious viruses. The presence of adventitious contaminating viruses may interfere with the results by leading to a higher number of plaques on the monolayers and subsequent false-negative results. This procedure is widely accepted for the inactivation of flaviviruses and alphaviruses. In this study, the thermostability of CHIKV was evaluated. Heat inactivation at 56°C for 30 min was demonstrated to be insufficient for the complete removal of infectious CHIKV virions present in the samples. This thermotolerance of CHIKV could compromise the accuracy of serum tests, and therefore longer treatment for greater than 120 min is recommended.

  12. Activity of andrographolide against chikungunya virus infection.

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    Wintachai, Phitchayapak; Kaur, Parveen; Lee, Regina Ching Hua; Ramphan, Suwipa; Kuadkitkan, Atichat; Wikan, Nitwara; Ubol, Sukathida; Roytrakul, Sittiruk; Chu, Justin Jang Hann; Smith, Duncan R

    2015-01-01

    Chikungunya virus (CHIKV) is a re-emerging mosquito-borne alphavirus that has recently engendered large epidemics around the world. There is no specific antiviral for treatment of patients infected with CHIKV, and development of compounds with significant anti-CHIKV activity that can be further developed to a practical therapy is urgently required. Andrographolide is derived from Andrographis paniculata, a herb traditionally used to treat a number of conditions including infections. This study sought to determine the potential of andrographolide as an inhibitor of CHIKV infection. Andrographolide showed good inhibition of CHIKV infection and reduced virus production by approximately 3log10 with a 50% effective concentration (EC50) of 77 μM without cytotoxicity. Time-of-addition and RNA transfection studies showed that andrographolide affected CHIKV replication and the activity of andrographolide was shown to be cell type independent. This study suggests that andrographolide has the potential to be developed further as an anti-CHIKV therapeutic agent. PMID:26384169

  13. Chikungunya virus and its mosquito vectors.

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    Higgs, Stephen; Vanlandingham, Dana

    2015-04-01

    Chikungunya virus (CHIKV), a mosquito-borne alphavirus of increasing public health significance, has caused large epidemics in Africa and the Indian Ocean basin; now it is spreading throughout the Americas. The primary vectors of CHIKV are Aedes (Ae.) aegypti and, after the introduction of a mutation in the E1 envelope protein gene, the highly anthropophilic and geographically widespread Ae. albopictus mosquito. We review here research efforts to characterize the viral genetic basis of mosquito-vector interactions, the use of RNA interference and other strategies for the control of CHIKV in mosquitoes, and the potentiation of CHIKV infection by mosquito saliva. Over the past decade, CHIKV has emerged on a truly global scale. Since 2013, CHIKV transmission has been reported throughout the Caribbean region, in North America, and in Central and South American countries, including Brazil, Columbia, Costa Rica, El Salvador, French Guiana, Guatemala, Guyana, Nicaragua, Panama, Suriname, and Venezuela. Closing the gaps in our knowledge of driving factors behind the rapid geographic expansion of CHIKV should be considered a research priority. The abundance of multiple primate species in many of these countries, together with species of mosquito that have never been exposed to CHIKV, may provide opportunities for this highly adaptable virus to establish sylvatic cycles that to date have not been seen outside of Africa. The short-term and long-term ecological consequences of such transmission cycles, including the impact on wildlife and people living in these areas, are completely unknown.

  14. Evidence for homologous recombination in Chikungunya Virus.

    Science.gov (United States)

    Casal, Pablo E; Chouhy, Diego; Bolatti, Elisa M; Perez, Germán R; Stella, Emma J; Giri, Adriana A

    2015-04-01

    Chikungunya Virus (CHIKV), a mosquito-transmitted alphavirus, causes acute fever and joint pain in humans. Recently, endemic CHIKV infection outbreaks have jeopardized public health in wider geographical regions. Here, we analyze the phylogenetic associations of CHIKV and explore the potential recombination events on 152 genomic isolates deposited in GenBank database. The CHIKV genotypes [West African, Asian, East/Central/South African (ECSA)], and a clear division of ECSA clade into three sub-groups (I-II-III), were defined by Bayesian analysis; similar results were obtained using E1 gene sequences. A nucleotide identity-based approach is provided to facilitate CHIKV classification within ECSA clade. Using seven methods to detect recombination, we found a statistically significant event (p-values range: 1.14×10(-7)-4.45×10(-24)) located within the nsP3 coding region. This finding was further confirmed by phylogenetic networks (PHI Test, p=0.004) and phylogenetic tree incongruence analysis. The recombinant strain, KJ679578/India/2011 (ECSA III), derives from viruses of ECSA III and ECSA I. Our study demonstrates that recombination is an additional mechanism of genetic diversity in CHIKV that might assist in the cross-species transmission process.

  15. Reemergence of chikungunya virus in Bo, Sierra Leone.

    Science.gov (United States)

    Ansumana, Rashid; Jacobsen, Kathryn H; Leski, Tomasz A; Covington, Andrea L; Bangura, Umaru; Hodges, Mary H; Lin, Baochuan; Bockarie, Alfred S; Lamin, Joseph M; Bockarie, Moses J; Stenger, David A

    2013-07-01

    We diagnosed 400 possible IgM-positive cases of chikungunya virus in Bo, Sierra Leone, during July 2012-January 2013 by using lateral flow immunoassays. Cases detected likely represent only a small fraction of total cases. Further laboratory testing is required to confirm this outbreak and characterize the virus. PMID:23764023

  16. Globalization of Chikungunya Virus: Threat to the U.S.

    Science.gov (United States)

    In August, 2004, Kenyan health authorities and partners identified chikungunya virus as the cause of the febrile epidemic in a coastal island city. The virus is transmitted by Aedes mosquitoes in tropical Africa and Asia; the fever is rarely fatal but can incapacitate for weeks. Control was delayed,...

  17. Virus Chikungunya in Colombia, a simple matter of time?

    Directory of Open Access Journals (Sweden)

    Marco González T.

    2014-06-01

    Full Text Available Chikungunya virus (CHIKV is an RNA alphavirus of the family Togaviridae. The alphaviruses consist of 29 species, including eastern, western, and Venezuelan equine encephalitis viruses among others. CHIKV is transmitted by vector mosquitoes, Aedes aegypti and Aedes albipictus, which are abundant in the South American tropics.

  18. Rapidly Evolving Outbreak of a Febrile Illness in Rural Haiti: The Importance of a Field Diagnosis of Chikungunya Virus in Remote Locations.

    Science.gov (United States)

    McGraw, Ian T; Dhanani, Naila; Ray, Lee Ann; Bentley, Regina M; Bush, Ruth L; Vanderpool, David M

    2015-11-01

    Although rarely fatal, chikungunya virus (CHIKV) infection can lead to chronic debilitating sequelae. We describe the outbreak of suspected CHIKV in 93 subjects who presented voluntarily over 2 months to a remote rural Haitian general medical clinic staffed by international health care providers. Diagnosis was made on clinical signs and symptoms because no serum analysis was available in this remote rural site. The subjects were 18.0 ± 16.2 (median ± standard deviation) years of age and were of similar gender distribution. The presenting vital signs included a temperature of 102.3°F ± 0.6°F with fever lasting for 3.0 ± 0.7 days. Symptoms mainly consisted of symmetrical polyarthralgias in 82.8%, headache in 28.0%, abdominal pain in 17.2%, cough in 8.6%, maculopapular rash in 30.0%, and extremity bullae in 12.9%. In 84.9% of subjects, symptoms persisted for 7.1 ± 8.3 days with 16.1% having ongoing disability due to persistent pain (≥ 14 days duration). There were no deaths. In Haiti, especially in remote, rural regions, the risk for CHIKV spread is high given the shortage of detection methods and treatment in this tropical climate and the lack of preventative efforts underway. Implications for global public health are likely, with outbreak expansion and spread to neighboring countries, including the United States. PMID:26565773

  19. Rapidly Evolving Outbreak of a Febrile Illness in Rural Haiti: The Importance of a Field Diagnosis of Chikungunya Virus in Remote Locations.

    Science.gov (United States)

    McGraw, Ian T; Dhanani, Naila; Ray, Lee Ann; Bentley, Regina M; Bush, Ruth L; Vanderpool, David M

    2015-11-01

    Although rarely fatal, chikungunya virus (CHIKV) infection can lead to chronic debilitating sequelae. We describe the outbreak of suspected CHIKV in 93 subjects who presented voluntarily over 2 months to a remote rural Haitian general medical clinic staffed by international health care providers. Diagnosis was made on clinical signs and symptoms because no serum analysis was available in this remote rural site. The subjects were 18.0 ± 16.2 (median ± standard deviation) years of age and were of similar gender distribution. The presenting vital signs included a temperature of 102.3°F ± 0.6°F with fever lasting for 3.0 ± 0.7 days. Symptoms mainly consisted of symmetrical polyarthralgias in 82.8%, headache in 28.0%, abdominal pain in 17.2%, cough in 8.6%, maculopapular rash in 30.0%, and extremity bullae in 12.9%. In 84.9% of subjects, symptoms persisted for 7.1 ± 8.3 days with 16.1% having ongoing disability due to persistent pain (≥ 14 days duration). There were no deaths. In Haiti, especially in remote, rural regions, the risk for CHIKV spread is high given the shortage of detection methods and treatment in this tropical climate and the lack of preventative efforts underway. Implications for global public health are likely, with outbreak expansion and spread to neighboring countries, including the United States.

  20. Single-Reaction Multiplex Reverse Transcription PCR for Detection of Zika, Chikungunya, and Dengue Viruses

    OpenAIRE

    Waggoner, Jesse J.; Gresh, Lionel; Mohamed-Hadley, Alisha; Ballesteros, Gabriela; Davila, Maria Jose Vargas; Tellez, Yolanda; Sahoo, Malaya K; Balmaseda, Angel; Harris, Eva; Pinsky, Benjamin A.

    2016-01-01

    Clinical manifestations of Zika virus, chikungunya virus, and dengue virus infections can be similar. To improve virus detection, streamline molecular workflow, and decrease test costs, we developed and evaluated a multiplex real-time reverse transcription PCR for these viruses.

  1. Simultaneous outbreaks of dengue, chikungunya and Zika virus infections: diagnosis challenge in a returning traveller with nonspecific febrile illness.

    Science.gov (United States)

    Moulin, E; Selby, K; Cherpillod, P; Kaiser, L; Boillat-Blanco, N

    2016-05-01

    Zika virus is an emerging flavivirus that is following the path of dengue and chikungunya. The three Aedes-borne viruses cause simultaneous outbreaks with similar clinical manifestations which represents a diagnostic challenge in ill returning travellers. We report the first Zika virus infection case imported to Switzerland and present a diagnostic algorithm. PMID:27006779

  2. Simultaneous outbreaks of dengue, chikungunya and Zika virus infections: diagnosis challenge in a returning traveller with nonspecific febrile illness

    Directory of Open Access Journals (Sweden)

    E. Moulin

    2016-05-01

    Full Text Available Zika virus is an emerging flavivirus that is following the path of dengue and chikungunya. The three Aedes-borne viruses cause simultaneous outbreaks with similar clinical manifestations which represents a diagnostic challenge in ill returning travellers. We report the first Zika virus infection case imported to Switzerland and present a diagnostic algorithm.

  3. Simultaneous outbreaks of dengue, chikungunya and Zika virus infections: diagnosis challenge in a returning traveller with nonspecific febrile illness.

    OpenAIRE

    Moulin E.; Selby K.; Cherpillod P.; Kaiser L; Boillat-Blanco N.

    2016-01-01

    Zika virus is an emerging flavivirus that is following the path of dengue and chikungunya. The three Aedes-borne viruses cause simultaneous outbreaks with similar clinical manifestations which represents a diagnostic challenge in ill returning travellers. We report the first Zika virus infection case imported to Switzerland and present a diagnostic algorithm.

  4. Simultaneous outbreaks of dengue, chikungunya and Zika virus infections: diagnosis challenge in a returning traveller with nonspecific febrile illness

    OpenAIRE

    Moulin, E.; Selby, K.; Cherpillod, P.; Kaiser, L; Boillat-Blanco, N.

    2016-01-01

    Zika virus is an emerging flavivirus that is following the path of dengue and chikungunya. The three Aedes-borne viruses cause simultaneous outbreaks with similar clinical manifestations which represents a diagnostic challenge in ill returning travellers. We report the first Zika virus infection case imported to Switzerland and present a diagnostic algorithm.

  5. Evidence for endemic chikungunya virus infections in Bandung, Indonesia

    NARCIS (Netherlands)

    Kosasih, H.; Mast, Q. de; Widjaja, S.; Sudjana, P.; Antonjaya, U.; Ma'roef, C.; Riswari, S.F.; Porter, K.R.; Burgess, T.H.; Alisjahbana, B.; Ven, A. van der; Williams, M.

    2013-01-01

    Chikungunya virus (CHIKV) is known to cause sporadic or explosive outbreaks. However, little is known about the endemic transmission of CHIKV. To ascertain the endemic occurrence of CHIKV transmission, we tested blood samples from patients with a non-dengue febrile illness who participated in a pros

  6. Chikungunya Virus Sequences Across the First Epidemic in Nicaragua, 2014-2015.

    Science.gov (United States)

    Wang, Chunling; Saborio, Saira; Gresh, Lionel; Eswarappa, Meghana; Wu, Diane; Fire, Andrew; Parameswaran, Poornima; Balmaseda, Angel; Harris, Eva

    2016-02-01

    Chikungunya is caused by the mosquito-borne arthrogenic alphavirus, chikungunya virus (CHIKV). Chikungunya was introduced into the Americas in late 2013 and Nicaragua in mid-2014. Here, we sequenced five imported and 30 autochthonous Nicaraguan CHIKV from cases identified in the first epidemic in the country between August 2014 and April 2015. One full-length and two partial genomic sequences were obtained by deep sequencing; Sanger methodology yielded 33 E1 sequences from five imported and 28 autochthonous cases. Phylogenetic analysis indicates that Nicaraguan CHIKV all belonged to the Asian genotype, Caribbean clade. Moreover, E1 gene sequences revealed accumulation of mutations in later months of the epidemic, including four silent mutations in 11 autochthonous cases and three non-synonymous mutations in three autochthonous cases. No mutations contributing to increased transmissibility by Aedes albopictus were identified in the E1 gene. This represents the most comprehensive set of CHIKV sequences available from the Americas to date. PMID:26643533

  7. Virus Chikungunya in Colombia, a simple matter of time?

    OpenAIRE

    Marco González T.; Salim Mattar V.

    2014-01-01

    Chikungunya virus (CHIKV) is an RNA alphavirus of the family Togaviridae. The alphaviruses consist of 29 species, including eastern, western, and Venezuelan equine encephalitis viruses among others. CHIKV is transmitted by vector mosquitoes, Aedes aegypti and Aedes albipictus, which are abundant in the South American tropics.CHIKV was first isolated in 1953 in the serum of a patient in Tanzania during an epidemic of dengue. In a recent dendrogram, this isolate appeared with the name of Ross l...

  8. Immunogenicity of Escherichia coli expressed envelope 2 protein of Chikungunya virus.

    Science.gov (United States)

    Tripathi, Nagesh K; Priya, Raj; Shrivastava, Ambuj

    2014-01-01

    Chikungunya fever, a re-emerging infection, is an arthropod-borne viral disease prevalent in different parts of the world, particularly Africa and South East Asia. Chikungunya virus envelope 2 protein is involved in binding to host receptors and it contains specific epitopes that elicit virus neutralizing antibodies. A highly immunogenic, recombinant Chikungunya virus envelope 2 protein was produced by bioreactor in Escherichia coli for development of a suitable diagnostic and vaccine candidate. This protein was refolded and further purified to achieve biologically active protein. The biological function of refolded and purified recombinant envelope 2 protein of Chikungunya virus was confirmed by its ability to generate envelope 2 specific antibodies with high titers in animal models. These findings suggest that recombinant envelope 2 protein of Chikungunya virus in combination with compatible adjuvant is highly immunogenic. Thus, recombinant envelope 2 protein can be a potential diagnostic reagent and vaccine candidate against Chikungunya virus infection.

  9. Assessment of flavaglines as potential chikungunya virus entry inhibitors.

    Science.gov (United States)

    Wintachai, Phitchayapak; Thuaud, Frédéric; Basmadjian, Christine; Roytrakul, Sittiruk; Ubol, Sukathida; Désaubry, Laurent; Smith, Duncan R

    2015-03-01

    Chikungunya virus (CHIKV) is a re-emerging mosquito-borne alphavirus that recently caused large epidemics in islands in, and countries around, the Indian Ocean. There is currently no specific drug for therapeutic treatment or for use as a prophylactic agent against infection and no commercially available vaccine. Prohibitin has been identified as a receptor protein used by chikungunya virus to enter mammalian cells. Recently, synthetic sulfonyl amidines and flavaglines (FLs), a class of naturally occurring plant compounds with potent anti-cancer and cytoprotective and neuroprotective activities, have been shown to interact directly with prohibitin. This study therefore sought to determine whether three prohibitin ligands (sulfonyl amidine 1 m and the flavaglines FL3 and FL23) were able to inhibit CHIKV infection of mammalian Hek293T/17 cells. All three compounds inhibited infection and reduced virus production when cells were treated before infection but not when added after infection. Pretreatment of cells for only 15 minutes prior to infection followed by washing out of the compound resulted in significant inhibition of entry and virus production. These results suggest that further investigation of prohibitin ligands as potential Chikungunya virus entry inhibitors is warranted.

  10. Molecular characterization of dengue and chikungunya virus strains circulating in New Delhi, India.

    Science.gov (United States)

    Afreen, Nazia; Deeba, Farah; Khan, Wajihul H; Haider, Shakir H; Kazim, Syed Naqui; Ishrat, Romana; Naqvi, Irshad Hussain; Shareef, Mohammad Y; Broor, Shobha; Ahmed, Anwar; Parveen, Shama

    2014-12-01

    Dengue and chikungunya are acute viral infections with overlapping clinical symptoms. Both diseases are transmitted by common mosquito vectors resulting in their co-circulation in a region. Molecular and serological tests specific for both dengue and chikungunya infections were performed on 87 acute phase blood samples collected from patients with suspected dengue/chikungunya infections in Delhi from September to December, 2011. RT-PCR and IgM ELISA were performed to detect dengue virus (DENV) and chikungunya virus (CHIKV). NS1 and IgG ELISA were also performed to detect DENV specific antigen and secondary DENV infection. DENV infection was detected in 49%, CHIKV infection in 29% and co-infection with DENV and CHIKV in 10% of the samples by RT-PCR. DENV serotypes 1, 2 and 3 were detected in this study. Nine DENV-1 strains, six DENV-2 strains and 20 CHIKV strains were characterized by DNA sequencing and phylogenetic analysis of their respective envelope protein genes. DENV-1 strains grouped in the American African genotype, DENV-2 strains in the Cosmopolitan genotype and CHIKV strains in the East Central South African genotype by phylogenetic analysis. This is one of the few studies reporting the phylogeny of two dengue virus serotypes (DENV-1 and DENV-2) and CHIKV. Surveillance and monitoring of DENV and CHIKV strains are important for design of strategies to control impending epidemics.

  11. Genetic characterization of Chikungunya virus in the Central African Republic.

    Science.gov (United States)

    Desdouits, Marion; Kamgang, Basile; Berthet, Nicolas; Tricou, Vianney; Ngoagouni, Carine; Gessain, Antoine; Manuguerra, Jean-Claude; Nakouné, Emmanuel; Kazanji, Mirdad

    2015-07-01

    Chikungunya virus (CHIKV) is an alphavirus transmitted by the bite of mosquito vectors. Over the past 10 years, the virus has gained mutations that enhance its transmissibility by the Aedes albopictus vector, resulting in massive outbreaks in the Indian Ocean, Asia and Central Africa. Recent introduction of competent A. albopictus vectors into the Central African Republic (CAR) pose a threat of a Chikungunya fever (CHIKF) epidemic in this region. We undertook this study to assess the genetic diversity and background of CHIKV strains isolated in the CAR between 1975 and 1984 and also to estimate the ability of local strains to adapt to A. albopictus. Our results suggest that, local CHIKV strains have a genetic background compatible with quick adaptation to A. albopictus, as previously observed in other Central African countries. Intense surveillance of the human and vector populations is necessary to prevent or anticipate the emergence of a massive CHIKF epidemic in the CAR.

  12. Co-distribution and Co-infection of Chikungunya and Dengue Viruses.

    OpenAIRE

    Furuya-Kanamori, L.; Liang, S.; Milinovich, G; Soares Magalhaes, RJ; Clements, AC; Hu, W; Brasil, P; Frentiu, FD; Dunning, R.; Yakob, L

    2016-01-01

    Background Chikungunya and dengue infections are spatio-temporally related. The current review aims to determine the geographic limits of chikungunya, dengue and the principal mosquito vectors for both viruses and to synthesise current epidemiological understanding of their co-distribution. Methods Three biomedical databases (PubMed, Scopus and Web of Science) were searched from their inception until May 2015 for studies that reported concurrent detection of chikungunya and dengue viruses in ...

  13. Co-distribution and Co-infection of Chikungunya and Dengue Viruses.

    OpenAIRE

    Furuya-Kanamori, Luis; Liang, Shaohong; Milinovich, Gabriel; Soares Magalhaes, Ricardo J.; Archie C.A. Clements; Hu, Wenbiao; Brasil, Patricia; Frentiu, Francesca D.; Dunning, Rebecca; Yakob, Laith

    2016-01-01

    Chikungunya and dengue infections are spatio-temporally related. The current review aims to determine the geographic limits of chikungunya, dengue and the principal mosquito vectors for both viruses and to synthesise current epidemiological understanding of their co-distribution. Three biomedical databases (PubMed, Scopus and Web of Science) were searched from their inception until May 2015 for studies that reported concurrent detection of chikungunya and dengue viruses in the same patient. A...

  14. Chikungunya virus and chikungunya fever%基孔肯雅病毒与基孔肯雅热

    Institute of Scientific and Technical Information of China (English)

    田德桥; 陈薇

    2016-01-01

    基孔肯雅热(chikungunya fever)是由基孔肯雅病毒(chikungunya virus)引起的一种蚊媒传染病,感染率高,可引起持续的关节症状。近几年来,基孔肯雅热暴发次数增加,流行范围不断扩大,全球范围内每年可导致100万人感染。同时,基孔肯雅病毒中某些基因突变使其可有效通过白纹伊蚊传播,不仅对热带和亚热带地区,还对白纹伊蚊广泛存在的温带地区的民众构成了潜在威胁。%Chikungunya fever is a mosquito‐borne infectious disease caused by chikungunya virus ,with high infection rate and persistent joint pain . In recent years , outbreak of chikungunya fever increased with expanding epidemic scope ,leading to one million infected cases each year worldwide .Meanwhile ,some chikungunya virus genotypes have gained some mutations which result in more effectively spread by Aedes albopictus .So it poses a potential threat to the residents not only in tropical and subtropical regions ,but also in temperate regions with Aedes albopictus .

  15. The green tea catechin, epigallocatechin gallate inhibits chikungunya virus infection.

    Science.gov (United States)

    Weber, Christopher; Sliva, Katja; von Rhein, Christine; Kümmerer, Beate M; Schnierle, Barbara S

    2015-01-01

    Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that causes chikungunya fever and has infected millions of people mainly in developing countries. The associated disease is characterized by rash, high fever and severe arthritis that can persist for years. CHIKV has adapted to Aedes albopictus, which also inhabits temperate regions, including Europe and the United States of America and might cause new, large outbreaks there. No treatment or licensed CHIKV vaccine exists. Epigallocatechin-3-gallate (EGCG), the major component of green tea, has, among other beneficial properties, antiviral activities. Therefore, we examined if EGCG has antiviral activity against CHIKV. EGCG inhibited CHIKV infection in vitro, blocked entry of CHIKV Env-pseudotyped lentiviral vectors and inhibited CHIKV attachment to target cells. Thus EGCG might be used as a lead structure to develop more effective antiviral drugs.

  16. Chikungunya virus,epidemiology,clinics and phylogenesis:A review

    Institute of Scientific and Technical Information of China (English)

    Alessandra; Lo; Presti; Alessia; Lai; Eleonora; Cella; Gianguglielmo; Zehender; Massimo; Ciccozzi

    2014-01-01

    Chikungunva virus is a mosquito-transmitted alphavirus that causes chikungunva fever,a febrile illness associated with severe arthralgia and rash.Chikungunva virus is transmitted by culicine mosquitoes:Chikungunya virus replicates in the skin,disseminates to liver,muscle,joints.lymphoid tissue and brain,presumably through the blood.Phylogenetic studies showed that the Indian Ocean and the Indian subcontinent epidemics were caused by two different introductions of distinct strains of East/Central/South African genotype of CHIKV.The paraphyletic grouping of African CHIK viruses supports the historical evidence that the virus was introduced into Asia from Africa.Phylogenetic analysis divided Chikungunva virus isolates into three distinct genotypes based on geographical origins:the first,the West Africa genotype,consisted of isolates from Senegal and Nigeria;the second contained strains from East/Central/South African genotype,while the third contained solely Asian.The most recent common ancestor for the recent epidemic,which ravaged Indian Ocean islands and Indian subcontinent in 2004- 2007.was found to date in 2002.Asian lineage dated about 1952 and exhibits similar spread patterns of the recent Indian Ocean outbreak lineage,with successive epidemics detected along an eastward path.Asian group splitted into two clades:an Indian lineage and a south east lineage.Outbreaks of Chikungunya virus fever in Asia have not been associated necessarily with outbreaks in Africa.Phylogenetic tools can reconstruct geographic spread of Chikungunva virus during the epidemics wave.The good management of patients with acute Chikungunva virus infection is essential for public health in susceptible areas with current Aedes spp activity.

  17. Inactivation of Chikungunya virus by 1,5 iodonapthyl azide

    Directory of Open Access Journals (Sweden)

    Sharma Anuj

    2012-12-01

    Full Text Available Abstract Background Chikungunya virus (CHIKV is an arthropod borne alphavirus of the family Togaviridae. CHIKV is a reemerging virus for which there is no safe prophylactic vaccine. A live attenuated strain of CHIKV, CHIK181/25, was previously demonstrated to be highly immunogenic in humans, however, it showed residual virulence causing transient arthralgia. Findings In this study, we demonstrate the complete inactivation of CHIKV181/25 by 1,5 iodonapthyl azide (INA. No cytopathic effect and virus replication was observed in cells infected with the INA-inactivated CHIKV. However, a reduction in the INA-inactivated CHIK virus-antibody binding capacity was observed by western blot analysis. Conclusion INA completely inactivated CHIKV and can further be explored for developing an inactivated-CHIKV vaccine.

  18. [Situational panorama of Mexico against the chikungunya virus pandemic].

    Science.gov (United States)

    Martínez-Sánchez, Abisai; Martínez-Ramos, Ericay Berenice; Chávez-Angeles, Manuel Gerardo

    2015-01-01

    Recent outbreaks of emerging diseases emphasize the vulnerability of health systems, as is the case of chikungunya fever. The wide geographical incidence of the virus in the last years requires alerting systems for the prevention, diagnosis, control and eradication of the disease. Given the ecological, epidemiological and socio-economic characteristic of Mexico, this disease affects directly or indirectly the health of the population and development of agricultural, livestock, industrial, fishing, oil and tourism activities in the country. Due to this situation it is essential to make a brief analysis on the main clinical data, epidemiological and preventive measures with which our country counts with to confront the situation. PMID:25760749

  19. Current research and clinical trials for a vaccine against Chikungunya virus

    Directory of Open Access Journals (Sweden)

    Singh P

    2013-08-01

    Full Text Available Priyanka Singh,1 Mala Chhabra,1 Veena Mittal,1 Pankaj Sharma,1 Moshahid A Rizvi,2 Lakhvir Singh Chauhan,1 Arvind Rai1 1National Centre for Disease Control, Sham Nath Marg, 2Department of Biosciences, Jamia Millia Islamia, New Delhi, India Abstract: Chikungunya infection is a self-limiting Aedes mosquito-borne arboviral disease with variable clinical manifestations, ranging from asymptomatic illness to a very severe and crippling arthralgia. Until recently, Chikungunya was a little known disease that re-emerged in 2005–2006, leading to major outbreaks on the Indian Ocean Islands and in South East Asia, and eventually extending its range to temperate regions. It drew global attention due to its explosive onset, extensive geographic distribution, and high morbidity. Since re-emergence, an estimated one million symptomatic cases with 0.1% fatality per year have been reported globally. A lack of herd immunity, vector control, and globalization and trade are clearly a problem in the spread of this disease. The Chikungunya virus (CHIKV has also acquired biologically important mutations during its evolution, increasing its geographic reach. This disease has resulted in a loss of productivity in affected communities. The absence of a vaccine or an effective antiviral therapy makes dealing with this disease challenging for those involved in public health. There is an emergent need for an effective vaccine against CHIKV infection. The candidates that have been tested include attenuated living, nonliving and genetically engineered vaccines. Several of these vaccine candidates are in preclinical and clinical trials. This review outlines the current knowledge about chikungunya infection and vaccine development. Keywords: Chikungunya, outbreaks, epidemics, genotypes, vaccines, therapy

  20. Diagnosis and management of imported Chikungunya fever in Taiwan: a case report.

    Science.gov (United States)

    Chang, Ko; Hsieh, Hsiao-Chen; Tsai, Jih-Jin; Lin, Wei-Ru; Lu, Po-Liang; Chen, Yen-Hsu

    2010-05-01

    Chikungunya virus, a mosquito-borne alphavirus, is endemic in Africa and Southeast Asia but is rarely reported in Taiwan. We report the case of a Taiwanese woman who developed Chikungunya fever, which was first diagnosed by a clinician rather than by fever screening at an airport. The woman presented with fever, maculopapular rash, and arthralgia, the triad for the disease, on the day she returned home after a trip to Malaysia. These symptoms are very similar to those of dengue fever, which is endemic in Southern Taiwan. Chikungunya infection was confirmed by reverse transcriptase-polymerase chain reaction and seroconversion on paired serum specimens. For approximately 40 years until 2006, no cases of Chikungunya fever had been found in Taiwan. Clinicians in Taiwan should consider Chikungunya fever as a possible diagnosis for a febrile patient with arthralgia, rash, and a history of travel to an endemic area, such as Africa or Southeast Asia. PMID:20466336

  1. Surveillance of chikungunya virus inAndhraPradesh,Southern India

    Institute of Scientific and Technical Information of China (English)

    CVMNareshKumar; P Sangamithra; M Rajasekhar; DVR Saigopal

    2010-01-01

    Objective:The study involved survey and screening of areas suspected of chikungunya virus (CHIKV)infection, characterizing the causative agent and identifying the circulatingCHIKV genotype.Methods: Acute phase samples were screened by the use ofRTPCR using primer setDVRChk-F/DVRChk-R whereas convalescent samples were tested byCHIKV IgM strips. Results: Two hundred and seventy five acute phase samples were screened by RT-PCR, of which 149(54.18%) showed positivity forCHIKV. Later on192 convalescent phase samples were tested forCHIKV specific antibodies in which125(65.10%) samples were found to be positive. Four CHIKV strains were selected and subjected to cloning followed by nucleotide sequencing and were submitted to the GenbankDNAdatabase with the Accession numbers(GQ119362,GQ119363, GQ119364, andFJ225403). The Sequence analysis of“CHIK-Kadapa” strain(GQ119362)with other CHIKV isolates suggested that the present CHIKV strain has (99.23± 0.52) % and100 %identity with Central East South African isolates(CESA) at nucleotide and amino acid levels respectively. Two unique non synonymous mutations S168L andD183Vwere depicted in E1 gene of the selected strains of the present study.Conclusions:The14 months survey revealed the circulation of CHIKV in2008-2009in Andhra Pradesh and the causative agent is identified to be of Central East South African(CESA) origin. The importance of the non synonymous mutations (S168L and D183V) and their role in the mobility and strength of theE1-E1andE1-E2 interactions needs further investigations. The study also urges the need for intensifying the epidemiological and entomological surveillance to combat any suchCHIKV outbreak in the near future.

  2. Single-Reaction Multiplex Reverse Transcription PCR for Detection of Zika, Chikungunya, and Dengue Viruses

    Science.gov (United States)

    Waggoner, Jesse J.; Gresh, Lionel; Mohamed-Hadley, Alisha; Ballesteros, Gabriela; Davila, Maria Jose Vargas; Tellez, Yolanda; Sahoo, Malaya K.; Balmaseda, Angel; Harris, Eva

    2016-01-01

    Clinical manifestations of Zika virus, chikungunya virus, and dengue virus infections can be similar. To improve virus detection, streamline molecular workflow, and decrease test costs, we developed and evaluated a multiplex real-time reverse transcription PCR for these viruses. PMID:27184629

  3. Single-Reaction Multiplex Reverse Transcription PCR for Detection of Zika, Chikungunya, and Dengue Viruses.

    Science.gov (United States)

    Waggoner, Jesse J; Gresh, Lionel; Mohamed-Hadley, Alisha; Ballesteros, Gabriela; Davila, Maria Jose Vargas; Tellez, Yolanda; Sahoo, Malaya K; Balmaseda, Angel; Harris, Eva; Pinsky, Benjamin A

    2016-07-01

    Clinical manifestations of Zika virus, chikungunya virus, and dengue virus infections can be similar. To improve virus detection, streamline molecular workflow, and decrease test costs, we developed and evaluated a multiplex real-time reverse transcription PCR for these viruses. PMID:27184629

  4. Development of Neutralization Assay Using an eGFP Chikungunya Virus

    Directory of Open Access Journals (Sweden)

    Cheng-Lin Deng

    2016-06-01

    Full Text Available Chikungunya virus (CHIKV, a member of the Alphavirus genus, is an important human emerging/re-emerging pathogen. Currently, there are no effective antiviral drugs or vaccines against CHIKV infection. Herein, we construct an infectious clone of CHIKV and an eGFP reporter CHIKV (eGFP-CHIKV with an isolated strain (assigned to Asian lineage from CHIKV-infected patients. The eGFP-CHIKV reporter virus allows for direct visualization of viral replication through the levels of eGFP expression. Using a known CHIKV inhibitor, ribavirin, we confirmed that the eGFP-CHIKV reporter virus could be used to identify inhibitors against CHIKV. Importantly, we developed a novel and reliable eGFP-CHIKV reporter virus-based neutralization assay that could be used for rapid screening neutralizing antibodies against CHIKV.

  5. Development of Neutralization Assay Using an eGFP Chikungunya Virus

    Science.gov (United States)

    Deng, Cheng-Lin; Liu, Si-Qing; Zhou, Dong-Gen; Xu, Lin-Lin; Li, Xiao-Dan; Zhang, Pan-Tao; Li, Peng-Hui; Ye, Han-Qing; Wei, Hong-Ping; Yuan, Zhi-Ming; Qin, Cheng-Feng; Zhang, Bo

    2016-01-01

    Chikungunya virus (CHIKV), a member of the Alphavirus genus, is an important human emerging/re-emerging pathogen. Currently, there are no effective antiviral drugs or vaccines against CHIKV infection. Herein, we construct an infectious clone of CHIKV and an eGFP reporter CHIKV (eGFP-CHIKV) with an isolated strain (assigned to Asian lineage) from CHIKV-infected patients. The eGFP-CHIKV reporter virus allows for direct visualization of viral replication through the levels of eGFP expression. Using a known CHIKV inhibitor, ribavirin, we confirmed that the eGFP-CHIKV reporter virus could be used to identify inhibitors against CHIKV. Importantly, we developed a novel and reliable eGFP-CHIKV reporter virus-based neutralization assay that could be used for rapid screening neutralizing antibodies against CHIKV. PMID:27367716

  6. Early Events in Chikungunya Virus Infection-From Virus Cell Binding to Membrane Fusion

    NARCIS (Netherlands)

    van Duijl-Richter, Mareike K. S.; Hoornweg, Tabitha E.; Rodenhuis-Zybert, Izabela A.; Smit, Jolanda M.

    2015-01-01

    Chikungunya virus (CHIKV) is a rapidly emerging mosquito-borne alphavirus causing millions of infections in the tropical and subtropical regions of the world. CHIKV infection often leads to an acute self-limited febrile illness with debilitating myalgia and arthralgia. A potential long-term complica

  7. Dynamics of chikungunya virus cell entry unraveled by single virus tracking in living cells

    NARCIS (Netherlands)

    Hoornweg, Tabitha E; van Duijl-Richter, Mareike K S; Ayala Nuñez, Nilda V; Albulescu, Irina C; van Hemert, Martijn J; Smit, Jolanda M

    2016-01-01

    Chikungunya virus (CHIKV) is a rapidly emerging mosquito-borne human pathogen causing major outbreaks in Africa, Asia and the Americas. The cell entry pathway hijacked by CHIKV to infect a cell has been studied before using inhibitory compounds. There has been some debate on the mechanism by which C

  8. A +RNA virus diptych : Chikungunya virus-host interactions and arteriviral programmed ribosomal frameshifting

    NARCIS (Netherlands)

    Treffers, Emma Elisabeth (Emmely)

    2015-01-01

    In part 1 of the thesis quantitative proteomics was used to determine changes in abundance and phosphorylation status of host proteins during infection with the human pathogen chikungunya virus (CHIKV). Several proteins were identified that may be specifically downregulated during CHIKV infection to

  9. Chikungunya virus outbreak in Kerala, India, 2007: a seroprevalence study.

    Science.gov (United States)

    Kumar, Narendran Pradeep; Suresh, Abidha; Vanamail, Perumal; Sabesan, Shanmugavelu; Krishnamoorthy, Kalianna Gounder; Mathew, Jacob; Jose, Varakilparambil Thomas; Jambulingam, Purushothaman

    2011-12-01

    India was affected by a major outbreak of chikungunya fever caused by Chikungunya virus (CHIKV) during 2006-2007. Kerala was the worst affected state during 2007 with a contribution of 55.8% suspected cases in the country. However, except for clinically reported case records, no systematic information is available on infection status of CHIKV in the region. Hence, we carried out a post-epidemic survey to estimate seroprevalence status [immunoglobulin G (IgG)] in the community using commercially available indirect immunofluorescence test. This methodology had been reported to be highly specific and sensitive for CHIKV infection. The study area selected was the worst affected mid-highlands region of Kerala which harbour vast area of rubber plantations. The study evidenced 68% of the population to be seropositive for CHIKV IgG. Males were found more affected than females (χ2 = 9.86; p = 0.002). Among males, prevalence was significantly higher in the age classes 21-30 (χ2 = 5.46; p = 0.019) and 31-40 (χ2 = 5.84; p = 0.016) years. This may be due to high occupational risk of the male population engaged in plantation activities exposed to infective bites of Aedes albopictus. The current study provides an insight into the magnitude of CHIKV outbreak in Kerala. PMID:22241110

  10. Chikungunya virus outbreak in Kerala, India, 2007: a seroprevalence study

    Directory of Open Access Journals (Sweden)

    Narendran Pradeep Kumar

    2011-12-01

    Full Text Available India was affected by a major outbreak of chikungunya fever caused by Chikungunya virus (CHIKV during 2006-2007. Kerala was the worst affected state during 2007 with a contribution of 55.8% suspected cases in the country. However, except for clinically reported case records, no systematic information is available on infection status of CHIKV in the region. Hence, we carried out a post-epidemic survey to estimate seroprevalence status [immunoglobulin G (IgG] in the community using commercially available indirect immunofluorescence test. This methodology had been reported to be highly specific and sensitive for CHIKV infection. The study area selected was the worst affected mid-highlands region of Kerala which harbour vast area of rubber plantations. The study evidenced 68% of the population to be seropositive for CHIKV IgG. Males were found more affected than females (χ2 = 9.86; p = 0.002. Among males, prevalence was significantly higher in the age classes 21-30 (χ2 = 5.46; p = 0.019 and 31-40 (χ2 = 5.84; p = 0.016 years. This may be due to high occupational risk of the male population engaged in plantation activities exposed to infective bites of Aedes albopictus. The current study provides an insight into the magnitude of CHIKV outbreak in Kerala.

  11. Cytokine levels in patients with chikungunya virus infection

    Institute of Scientific and Technical Information of China (English)

    Chintana Chirathaworn; Yong Poovorawan; Somrat Lertmaharit; Norra Wuttirattanakowit

    2013-01-01

    Objective:To investigate cytokine profile in patients with chikungunya virus (CHIKV) infection. Methods: Twenty eight pairs of serum samples collected from CHIKV infected patients during the outbreak of chikungunya fever in South Thailand in 2008 were obtained. A multiple cytokine assay for detection of 17 cytokines was performed. Results:In the acute stage of CHIKV infection, the patients had significantly higher levels of interleukin-6, granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, monocyte chemotactic protein 1 and tumor necrosis factor alpha than the control (P<0.001, P=0.023, P=0.015, P<0.001 and P=0.024, respectively). When the disease developed to the recovery stage, the patients had significantly lower levels of interleukin-6, granulocyte-macrophage colony-stimulating factor, monocyte chemotactic protein 1 and macrophage inflammatory protein beta than in the acute stage (P<0.001). Conclusions:This study provides additional information that these cytokines could play roles in pathogenesis of CHIKV infection and could be used as disease biomarkers or drug targets.

  12. Prevalence of dengue and chikungunya virus infections in north-eastern Tanzania

    DEFF Research Database (Denmark)

    Kajeguka, Debora C; Kaaya, Robert D; Mwakalinga, Steven;

    2016-01-01

    and chikungunya virus among participants presenting with malaria-like symptoms (fever, headache, rash, vomit, and joint pain) in three communities with distinct ecologies of north-eastern Tanzania. METHODS: Cross sectional studies were conducted among 1100 participants (aged 2-70 years) presenting with malaria....... Further analyses revealed that headache and joint pain were significantly associated with chikungunya IgM seropositivity. CONCLUSION: In north-eastern Tanzania, mainly chikungunya virus appears to be actively circulating in the population. Continuous surveillance is needed to determine the contribution...

  13. Destructive arthritis in a patient with chikungunya virus infection with persistent specific IgM antibodies

    Directory of Open Access Journals (Sweden)

    Receveur Marie-Catherine

    2009-12-01

    Full Text Available Abstract Background Chikungunya fever is an emerging arboviral disease characterized by an algo-eruptive syndrome, inflammatory polyarthralgias, or tenosynovitis that can last for months to years. Up to now, the pathophysiology of the chronic stage is poorly understood. Case presentation We report the first case of CHIKV infection with chronic associated rheumatism in a patient who developed progressive erosive arthritis with expression of inflammatory mediators and persistence of specific IgM antibodies over 24 months following infection. Conclusions Understanding the specific features of chikungunya virus as well as how the virus interacts with its host are essential for the prevention, treatment or cure of chikungunya disease.

  14. Spatial and Temporal Clustering of Chikungunya Virus Transmission in Dominica.

    Directory of Open Access Journals (Sweden)

    Elaine O Nsoesie

    Full Text Available Using geo-referenced case data, we present spatial and spatio-temporal cluster analyses of the early spread of the 2013-2015 chikungunya virus (CHIKV in Dominica, an island in the Caribbean. Spatial coordinates of the locations of the first 417 reported cases observed between December 15th, 2013 and March 11th, 2014, were captured using the Global Positioning System (GPS. We observed a preponderance of female cases, which has been reported for CHIKV outbreaks in other regions. We also noted statistically significant spatial and spatio-temporal clusters in highly populated areas and observed major clusters prior to implementation of intensive vector control programs suggesting early vector control measures, and education had an impact on the spread of the CHIKV epidemic in Dominica. A dynamical identification of clusters can lead to local assessment of risk and provide opportunities for targeted control efforts for nations experiencing CHIKV outbreaks.

  15. Suramin inhibits chikungunya virus replication through multiple mechanisms.

    Science.gov (United States)

    Albulescu, Irina C; van Hoolwerff, Marcella; Wolters, Laura A; Bottaro, Elisabetta; Nastruzzi, Claudio; Yang, Shih Chi; Tsay, Shwu-Chen; Hwu, Jih Ru; Snijder, Eric J; van Hemert, Martijn J

    2015-09-01

    Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes severe and often persistent arthritis. In recent years, millions of people have been infected with this virus for which registered antivirals are still lacking. Using our recently established in vitro assay, we discovered that the approved anti-parasitic drug suramin inhibits CHIKV RNA synthesis (IC50 of ∼5μM). The compound inhibited replication of various CHIKV isolates in cell culture with an EC50 of ∼80μM (CC50>5mM) and was also active against Sindbis virus and Semliki Forest virus. In vitro studies hinted that suramin interferes with (re)initiation of RNA synthesis, whereas time-of-addition studies suggested it to also interfere with a post-attachment early step in infection, possibly entry. CHIKV (nsP4) mutants resistant against favipiravir or ribavirin, which target the viral RNA polymerase, did not exhibit cross-resistance to suramin, suggesting a different mode of action. The assessment of the activity of a variety of suramin-related compounds in cell culture and the in vitro assay for RNA synthesis provided more insight into the moieties required for antiviral activity. The antiviral effect of suramin-containing liposomes was also analyzed. Its approved status makes it worthwhile to explore the use of suramin to prevent and/or treat CHIKV infections.

  16. Identification of chikungunya virus interacting proteins in mammalian cells

    Indian Academy of Sciences (India)

    Mandar S Paingankar; Vidya A Arankalle

    2014-06-01

    Identification and characterization of virus host interactions is an essential step for the development of novel antiviral strategies. Very few studies have been targeted towards identification of chikungunya virus (CHIKV) interacting host proteins. In current study, virus overlay protein binding assay (VOPBA) and matrix-assisted laser desorption/ionization time of flight analysis (MALDI TOF/TOF) were employed for the identification of CHIKV binding proteins in mammalian cells. HSP70 and actin were identified as virus binding proteins in HEK-293T and Vero-E6 cells, whereas STAT-2 was identified as an additional protein in Vero-E6 cells. Pre-incubation with anti-HSP70 antibody and miRNA silencing of HSP70 significantly reduced the CHIKV production in HEK-293T and Vero-E6 cells at early time points. These results suggest that CHIKV exploits the housekeeping molecules such as actin, HSP70 and STAT-2 to establish infection in the mammalian cells.

  17. Evidence for endemic chikungunya virus infections in Bandung, Indonesia.

    Directory of Open Access Journals (Sweden)

    Herman Kosasih

    Full Text Available Chikungunya virus (CHIKV is known to cause sporadic or explosive outbreaks. However, little is known about the endemic transmission of CHIKV. To ascertain the endemic occurrence of CHIKV transmission, we tested blood samples from patients with a non-dengue febrile illness who participated in a prospective cohort study of factory workers in Bandung, Indonesia. From August 2000 to June 2004, and September 2006 to April 2008, 1901 febrile episodes occurred and 231 (12.2% dengue cases were identified. The remaining febrile cases were evaluated for possible CHIKV infection by measuring anti-CHIKV IgM and IgG antibodies in acute and convalescent samples. Acute samples of serologically positive cases were subsequently tested for the presence of CHIKV RNA by RT-PCR and/or virus isolation. A total of 135 (7.1% CHIKV infections were identified, providing an incidence rate of 10.1/1,000 person years. CHIKV infections were identified all year round and tended to increase during the rainy season (January to March. Severe illness was not found and severe arthralgia was not a prominently reported symptom. Serial post-illness samples from nine cases were tested to obtain a kinetic picture of IgM and IgG anti-CHIKV antibodies. Anti-CHIKV IgM antibodies were persistently detected in high titers for approximately one year. Three patients demonstrated evidence of possible sequential CHIKV infections. The high incidence rate and continuous chikungunya cases in this adult cohort suggests that CHIKV is endemically transmitted in Bandung. Further characterization of the circulating strains and surveillance in larger areas are needed to better understand CHIKV epidemiology in Indonesia.

  18. Preparation of vesicular stomatitis virus pseudotype with Chikungunya virus envelope protein.

    Science.gov (United States)

    Tong, W; Yin, X-X; Lee, B-J; Li, Y-G

    2015-06-01

    Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that causes Chikungunya fever (CHIKF) in millions of people mainly in developing countries. CHIKF is characterized by high fever, fatigue, headache, nausea, vomiting, rash, myalgia and severe arthralgia. To date, there is no specific treatment and no licensed vaccine against CHIKV infection. In this study, we developed a safe, efficient and easy neutralization assay of CHIKV based on vesicular stomatitis virus (VSV) pseudotype with CHIKV envelope protein and the green fluorescent protein (GFP) or luciferase as reporter gene, which could be used under a reduced safety level. The VSV pseudotype can be applied to the epidemic survey by measuring the expression of GFP or luciferase activity in infected cells. This system can also be used to study the mechanisms of virus entry.

  19. Monoclonal antibody targeting chikungunya virus envelope 1 protein inhibits virus release.

    Science.gov (United States)

    Masrinoul, Promsin; Puiprom, Orapim; Tanaka, Atsushi; Kuwahara, Miwa; Chaichana, Panjaporn; Ikuta, Kazuyoshi; Ramasoota, Pongrama; Okabayashi, Tamaki

    2014-09-01

    Chikungunya virus (CHIKV) causes an acute clinical illness characterized by sudden high fever, intense joint pain, and skin rash. Recent outbreaks of chikungunya disease in Africa and Asia are a major public health concern; however, there is currently no effective licensed vaccine or specific treatment. This study reported the development of a mouse monoclonal antibody (MAb), CK47, which recognizes domain III within the viral envelope 1 protein and inhibited the viral release process, thereby preventing the production of progeny virus. The MAb had no effect on virus entry and replication processes. Thus, CK47 may be a useful tool for studying the mechanisms underlying CHIKV release and may show potential as a therapeutic agent.

  20. Four emerging arboviral diseases in North America: Jamestown Canyon, Powassan, chikungunya, and Zika virus diseases.

    Science.gov (United States)

    Pastula, Daniel M; Smith, Daniel E; Beckham, J David; Tyler, Kenneth L

    2016-06-01

    Arthropod-borne viruses, or arboviruses, are viruses that are transmitted through the bites of mosquitoes, ticks, or sandflies. There are numerous arboviruses throughout the world capable of causing human disease spanning different viral families and genera. Recently, Jamestown Canyon, Powassan, chikungunya, and Zika viruses have emerged as increasingly important arboviruses that can cause human disease in North America. Unfortunately, there are currently no proven disease-modifying therapies for these arboviral diseases, so treatment is largely supportive. Given there are also no commercially available vaccines for these four arboviral infections, prevention is the key. To prevent mosquito or tick bites that might result in one of these arboviral diseases, people should wear long-sleeved shirts and pants while outside if feasible, apply insect repellant when going outdoors, using window screens or air conditioning to keep mosquitoes outside, and perform tick checks after being in wooded or brushy outdoor areas. PMID:26903031

  1. Seroprevalence of Anti-Chikungunya Virus Antibodies in Children and Adults in Managua, Nicaragua, After the First Chikungunya Epidemic, 2014-2015.

    Directory of Open Access Journals (Sweden)

    Guillermina Kuan

    2016-06-01

    Full Text Available Chikungunya is a viral disease transmitted by Aedes aegypti and Ae. albopictus mosquitoes. In late 2013, chikungunya virus (CHIKV was introduced into the Caribbean island of St. Martin. Since then, approximately 2 million chikungunya cases have been reported by the Pan American Health Organization, and most countries in the Americas report autochthonous transmission of CHIKV. In Nicaragua, the first imported case was described in July 2014 and the first autochthonous case in September 2014. Here, we conducted two studies to analyze the seroprevalence of anti-CHIKV antibodies after the first chikungunya epidemic in a community-based cohort study (ages 2-14 years and in a cross-sectional survey of persons aged ≥15 years in the same area of Managua, Nicaragua. Routine annual serum samples collected from 3,362 cohort participants in March/April 2014 and 2015, and 848 age-stratified samples collected from persons ≥15 years old at the end of May-beginning of June 2015 were used to estimate the seroprevalence of anti-CHIKV antibodies after the first epidemic (October 2014 to February 2015 in the study population. Using an Inhibition ELISA assay that measures total anti-CHIKV antibodies, the seroprevalence was significantly higher in those aged ≥15 (13.1% (95%CI: 10.9, 15.5 than in the pediatric population (6.1% (95%CI: 5.3, 6.9. The proportion of inapparent infections was 58.3% (95%CI: 51.5, 65.1 in children and 64.9% (95%CI: 55.2, 73.7 in the ≥15 study population. We identified age, water availability, household size, and socioeconomic status as factors associated with the presence of anti-CHIKV antibodies. Overall, this is the first report of CHIKV seropositivity in continental Latin America and provides useful information for public health authorities in the region.

  2. Seroprevalence of Anti-Chikungunya Virus Antibodies in Children and Adults in Managua, Nicaragua, After the First Chikungunya Epidemic, 2014-2015.

    Science.gov (United States)

    Kuan, Guillermina; Ramirez, Stephania; Gresh, Lionel; Ojeda, Sergio; Melendez, Marlon; Sanchez, Nery; Collado, Damaris; Garcia, Nadezna; Mercado, Juan Carlos; Gordon, Aubree; Balmaseda, Angel; Harris, Eva

    2016-06-01

    Chikungunya is a viral disease transmitted by Aedes aegypti and Ae. albopictus mosquitoes. In late 2013, chikungunya virus (CHIKV) was introduced into the Caribbean island of St. Martin. Since then, approximately 2 million chikungunya cases have been reported by the Pan American Health Organization, and most countries in the Americas report autochthonous transmission of CHIKV. In Nicaragua, the first imported case was described in July 2014 and the first autochthonous case in September 2014. Here, we conducted two studies to analyze the seroprevalence of anti-CHIKV antibodies after the first chikungunya epidemic in a community-based cohort study (ages 2-14 years) and in a cross-sectional survey of persons aged ≥15 years in the same area of Managua, Nicaragua. Routine annual serum samples collected from 3,362 cohort participants in March/April 2014 and 2015, and 848 age-stratified samples collected from persons ≥15 years old at the end of May-beginning of June 2015 were used to estimate the seroprevalence of anti-CHIKV antibodies after the first epidemic (October 2014 to February 2015 in the study population). Using an Inhibition ELISA assay that measures total anti-CHIKV antibodies, the seroprevalence was significantly higher in those aged ≥15 (13.1% (95%CI: 10.9, 15.5)) than in the pediatric population (6.1% (95%CI: 5.3, 6.9)). The proportion of inapparent infections was 58.3% (95%CI: 51.5, 65.1) in children and 64.9% (95%CI: 55.2, 73.7) in the ≥15 study population. We identified age, water availability, household size, and socioeconomic status as factors associated with the presence of anti-CHIKV antibodies. Overall, this is the first report of CHIKV seropositivity in continental Latin America and provides useful information for public health authorities in the region. PMID:27322692

  3. Clinical and virological characterization of imported cases of Chikungunya fever.

    Science.gov (United States)

    Pfeffer, Martin; Zöller, Gudrun; Essbauer, Sandra; Tomaso, Herbert; Behrens-Riha, Nicole; Löscher, Thomas; Dobler, Gerhard

    2008-01-01

    A Chikungunya virus (CHIKV) epidemic emerged in the Indian Ocean islands of the Comores, Reunion, Mayotte, Mauritius, the Seychelles and Madagascar in 2005 resulting in the infection of about 250.000 inhabitants and travellers in only one year. Beginning in March 2006 increasing numbers of CHIKV-like febrile illnesses were reported from various parts of India. We investigated 70 consecutive German travellers returning from the affected areas and presenting with arthralgia and/or fever suggestive of CHIKV infection. Eleven patients had serological evidence of CHIKV infection. Real-time RT-PCR for CHIKV was positive in two cases, one who returned from Mauritius and the other who came back from Rajasthan, Northern India. In both cases CHIKV was isolated and sequencing of the entire viral genome was performed. The nucleotide sequence data obtained for both CHIKV strains revealed a high level of identity to CHIKV isolates from the ongoing epidemic. In detail, we found only 18 nucleotide exchanges between the isolates from Mauritius and Rajasthan, resulting in only six amino acid changes (nsP1 T128K, T376M, nsP3 S472N, capsid P23S, V27I and E1-protein A226V). Although the excessive dimension of the 2005/2006 outbreak in the Indian Ocean islands was at least in part accounted to the naïve population affected, our results of the Rajasthan isolate support that the emergence of this CHIKV subtype may rather be a result of a better viral fitness. This has been previously accounted to a A226V change in the E1 protein of the new CHIKV variant when compared to other CHIKV data available. This mutation, supposedly resulting in high-titred viremia in humans and/or an enhanced adaptation to the vector population resulting in increased transmission rates, was also found in our CHIKV isolate from Mauritius. The spread of an African CHIKV to Asia further demonstrates how fast viruses can emerge and establish in places where competent vectors are prevalent.

  4. Early clearance of Chikungunya virus in children is associated with a strong innate immune response.

    Science.gov (United States)

    Simarmata, Diane; Ng, David Chun Ern; Kam, Yiu-Wing; Lee, Bernett; Sum, Magdline Sia Henry; Her, Zhisheng; Chow, Angela; Leo, Yee-Sin; Cardosa, Jane; Perera, David; Ooi, Mong H; Ng, Lisa F P

    2016-01-01

    Chikungunya fever (CHIKF) is a global infectious disease which can affect a wide range of age groups. The pathological and immunological response upon Chikungunya virus (CHIKV) infection have been reported over the last few years. However, the clinical profile and immune response upon CHIKV infection in children remain largely unknown. In this study, we analyzed the clinical and immunological response, focusing on the cytokine/chemokine profile in a CHIKV-infected pediatric cohort from Sarawak, Malaysia. Unique immune mediators triggered upon CHIKV infection were identified through meta-analysis of the immune signatures between this pediatric group and cohorts from previous outbreaks. The data generated from this study revealed that a broad spectrum of cytokines/chemokines is up-regulated in a sub-group of virus-infected children stratified according to their viremic status during hospitalization. Furthermore, different immune mediator profiles (the levels of pro-inflammatory cytokines, chemokines and growth and other factors) were observed between children and adults. This study gives an important insight to understand the immune response of CHIKV infection in children and would aid in the development of better prognostics and clinical management for children. PMID:27180811

  5. Effective Chikungunya Virus-like Particle Vaccine Produced in Insect Cells

    NARCIS (Netherlands)

    Metz, S.W.H.; Gardner, J.; Geertsema, C.; Le, T.T.; Goh, L.; Vlak, J.M.; Suhrbier, A.; Pijlman, G.P.

    2013-01-01

    The emerging arthritogenic, mosquito-borne chikungunya virus (CHIKV) causes severe disease in humans and represents a serious public health threat in countries where Aedes spp mosquitoes are present. This study describes for the first time the successful production of CHIKV virus-like particles (VLP

  6. Chikungunya Virus in Febrile Humans and Aedes aegypti Mosquitoes, Yucatan, Mexico

    Science.gov (United States)

    Cigarroa-Toledo, Nohemi; Blitvich, Bradley J.; Cetina-Trejo, Rosa C.; Talavera-Aguilar, Lourdes G.; Baak-Baak, Carlos M.; Torres-Chablé, Oswaldo M.; Hamid, Md-Nafiz; Friedberg, Iddo; González-Martinez, Pedro; Alonzo-Salomon, Gabriela; Rosado-Paredes, Elsy P.; Rivero-Cárdenas, Nubia; Reyes-Solis, Guadalupe C.; Farfan-Ale, Jose A.; Garcia-Rejon, Julian E.

    2016-01-01

    Chikungunya virus (CHIKV) was isolated from 12 febrile humans in Yucatan, Mexico, in 2015. One patient was co-infected with dengue virus type 1. Two additional CHIKV isolates were obtained from Aedes aegypti mosquitoes collected in the homes of patients. Phylogenetic analysis showed that the CHIKV isolates belong to the Asian lineage. PMID:27347760

  7. Longitudinal Analysis of Natural Killer Cells in Dengue Virus-Infected Patients in Comparison to Chikungunya and Chikungunya/Dengue Virus-Infected Patients.

    Directory of Open Access Journals (Sweden)

    Caroline Petitdemange

    2016-03-01

    Full Text Available Dengue virus (DENV is the most prominent arbovirus worldwide, causing major epidemics in South-East Asia, South America and Africa. In 2010, a major DENV-2 outbreak occurred in Gabon with cases of patients co-infected with chikungunya virus (CHIKV. Although the innate immune response is thought to be of primordial importance in the development and outcome of arbovirus-associated pathologies, our knowledge of the role of natural killer (NK cells during DENV-2 infection is in its infancy.We performed the first extensive comparative longitudinal characterization of NK cells in patients infected by DENV-2, CHIKV or both viruses. Hierarchical clustering and principal component analyses were performed to discriminate between CHIKV and DENV-2 infected patients.We observed that both activation and differentiation of NK cells are induced during the acute phase of infection by DENV-2 and CHIKV. Combinatorial analysis however, revealed that both arboviruses induced two different signatures of NK-cell responses, with CHIKV more associated with terminal differentiation, and DENV-2 with inhibitory KIRs. We show also that intracellular production of interferon-γ (IFN-γ by NK cells is strongly stimulated in acute DENV-2 infection, compared to CHIKV.Although specific differences were observed between CHIKV and DENV-2 infections, the significant remodeling of NK cell populations observed here suggests their potential roles in the control of both infections.

  8. Emergence of chikungunya virus in Indian subcontinent after 32 years: a review

    Directory of Open Access Journals (Sweden)

    Chandrakant Lahariya , S.K. Pradhan

    2006-12-01

    Full Text Available An outbreak of chikungunya virus is currently ongoing in many countries in Indian Ocean sinceJanuary 2005. The current outbreak appears to be the most severe and one of the biggest outbreakscaused by this virus. India, where this virus was last reported in 1973, is also amongst affectedcountries. Chikungunya virus has affected millions of the people in Africa and Southeast Asia, sinceit was first reported in 1952 in Tanzania. Even then, natural history of this disease is not fully understood.The intra-outbreak studies, point towards recent changes in the viral genome facilitatingthe rapid spread and enhanced pathogenecity. The available published scientific literature on chikungunyavirus was searched to understand the natural history of this disease, reasons for the currentoutbreak and the causes behind re-emergence of the virus in India.The paucity of the scientific information on various epidemiological aspects of chikungunya virusthreatens off an epidemic as control of spread of virus might be difficult in the absence of appropriateknowledge. There is an immediate need of the research on chikungunya virus, for an effectivevaccine besides strengthening the existing diagnostic laboratory facilities. The current outbreak canalso be taken as a lesson for establishment of a system for continuous surveillance of diseases, considereddisappeared from the countries. The re-emergence and epidemics are unpredictable phenomenabut the impact of such events can be ameliorated by appropriate knowledge and by being in theright state of preparedness

  9. Differential proteome analysis of chikungunya virus infection on host cells.

    Directory of Open Access Journals (Sweden)

    Christina Li-Ping Thio

    Full Text Available BACKGROUND: Chikungunya virus (CHIKV is an emerging mosquito-borne alphavirus that has caused multiple unprecedented and re-emerging outbreaks in both tropical and temperate countries. Despite ongoing research efforts, the underlying factors involved in facilitating CHIKV replication during early infection remains ill-characterized. The present study serves to identify host proteins modulated in response to early CHIKV infection using a proteomics approach. METHODOLOGY AND PRINCIPAL FINDINGS: The whole cell proteome profiles of CHIKV-infected and mock control WRL-68 cells were compared and analyzed using two-dimensional gel electrophoresis (2-DGE. Fifty-three spots were found to be differentially modulated and 50 were successfully identified by MALDI-TOF/TOF. Eight were significantly up-regulated and 42 were down-regulated. The mRNA expressions of 15 genes were also found to correlate with the corresponding protein expression. STRING network analysis identified several biological processes to be affected, including mRNA processing, translation, energy production and cellular metabolism, ubiquitin-proteasome pathway (UPP and cell cycle regulation. CONCLUSION/SIGNIFICANCE: This study constitutes a first attempt to investigate alteration of the host cellular proteome during early CHIKV infection. Our proteomics data showed that during early infection, CHIKV affected the expression of proteins that are involved in mRNA processing, host metabolic machinery, UPP, and cyclin-dependent kinase 1 (CDK1 regulation (in favour of virus survival, replication and transmission. While results from this study complement the proteomics results obtained from previous late host response studies, functional characterization of these proteins is warranted to reinforce our understanding of their roles during early CHIKV infection in humans.

  10. Chikungunya risk for Brazil

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    Raimunda do Socorro da Silva Azevedo

    2015-01-01

    Full Text Available This study aimed to show, based on the literature on the subject, the potential for dispersal and establishment of the chikungunya virus in Brazil. The chikungunya virus, a Togaviridae member of the genusAlphavirus, reached the Americas in 2013 and, the following year, more than a million cases were reported. In Brazil, indigenous transmission was registered in Amapa and Bahia States, even during the period of low rainfall, exposing the whole country to the risk of virus spreading. Brazil is historically infested by Ae. aegypti and Ae. albopictus, also dengue vectors. Chikungunya may spread, and it is important to take measures to prevent the virus from becoming endemic in the country. Adequate care for patients with chikungunya fever requires training general practitioners, rheumatologists, nurses, and experts in laboratory diagnosis. Up to November 2014, more than 1,000 cases of the virus were reported in Brazil. There is a need for experimental studies in animal models to understand the dynamics of infection and the pathogenesis as well as to identify pathophysiological mechanisms that may contribute to identifying effective drugs against the virus. Clinical trials are needed to identify the causal relationship between the virus and serious injuries observed in different organs and joints. In the absence of vaccines or effective drugs against the virus, currently the only way to prevent the disease is vector control, which will also reduce the number of cases of dengue fever.

  11. Inflammatory cytokine expression is associated with chikungunya virus resolution and symptom severity.

    Directory of Open Access Journals (Sweden)

    Alyson A Kelvin

    2011-08-01

    Full Text Available The Chikungunya virus infection zones have now quickly spread from Africa to parts of Asia, North America and Europe. Originally thought to trigger a disease of only mild symptoms, recently Chikungunya virus caused large-scale fatalities and widespread economic loss that was linked to recent virus genetic mutation and evolution. Due to the paucity of information on Chikungunya immunological progression, we investigated the serum levels of 13 cytokines/chemokines during the acute phase of Chikungunya disease and 6- and 12-month post-infection follow-up from patients of the Italian outbreak. We found that CXCL9/MIG, CCL2/MCP-1, IL-6 and CXCL10/IP-10 were significantly raised in the acute phase compared to follow-up samples. Furthermore, IL-1β, TNF-α, Il-12, IL-10, IFN-γ and IL-5 had low initial acute phase levels that significantly increased at later time points. Analysis of symptom severity showed association with CXCL9/MIG, CXCL10/IP-10 and IgG levels. These data give insight into Chikungunya disease establishment and subsequent convalescence, which is imperative to the treatment and containment of this quickly evolving and frequently re-emerging disease.

  12. Molecular modeling and docking study to elucidate novel chikungunya virus nsP2 protease inhibitors

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    T Agarwal

    2015-01-01

    Full Text Available Chikungunya is one of the tropical viral infections that severely affect the Asian and African countries. Absence of any suitable drugs or vaccines against Chikungunya virus till date makes it essential to identify and develop novel leads for the same. Recently, nsP2 cysteine protease has been classified as a crucial drug target to combat infections caused by Alphaviruses including Chikungunya virus due to its involvement viral replication. Here in, we investigated the structural aspects of the nsP2 protease through homology modeling based on nsP2 protease from Venezuelan equine encephalitis virus. Further, the ligands were virtually screened based on various pharmacological, ADME/Tox filters and subjected to docking with the modeled Chikungunya nsP2 protease using AutoDock4.2. The interaction profiling of ligand with the protein was carried out using LigPlot+. The results demonstrated that the ligand with PubChem Id (CID_5808891 possessed highest binding affinity towards Chikungunya nsP2 protease with a good interaction profile with the active site residues. We hereby propose that these compounds could inhibit the nsP2 protease by binding to its active site. Moreover, they may provide structural scaffold for the design of novel leads with better efficacy and specificity for the nsP2 protease.

  13. Inflammatory Cytokine Expression Is Associated with Chikungunya Virus Resolution and Symptom Severity

    Science.gov (United States)

    Kelvin, Alyson A.; Banner, David; Silvi, Giuliano; Moro, Maria Luisa; Spataro, Nadir; Gaibani, Paolo; Cavrini, Francesca; Pierro, Anna; Rossini, Giada; Cameron, Mark J.; Bermejo-Martin, Jesus F.; Paquette, Stéphane G.; Xu, Luoling; Danesh, Ali; Farooqui, Amber; Borghetto, Ilaria; Kelvin, David J.; Sambri, Vittorio; Rubino, Salvatore

    2011-01-01

    The Chikungunya virus infection zones have now quickly spread from Africa to parts of Asia, North America and Europe. Originally thought to trigger a disease of only mild symptoms, recently Chikungunya virus caused large-scale fatalities and widespread economic loss that was linked to recent virus genetic mutation and evolution. Due to the paucity of information on Chikungunya immunological progression, we investigated the serum levels of 13 cytokines/chemokines during the acute phase of Chikungunya disease and 6- and 12-month post-infection follow-up from patients of the Italian outbreak. We found that CXCL9/MIG, CCL2/MCP-1, IL-6 and CXCL10/IP-10 were significantly raised in the acute phase compared to follow-up samples. Furthermore, IL-1β, TNF-α, Il-12, IL-10, IFN-γ and IL-5 had low initial acute phase levels that significantly increased at later time points. Analysis of symptom severity showed association with CXCL9/MIG, CXCL10/IP-10 and IgG levels. These data give insight into Chikungunya disease establishment and subsequent convalescence, which is imperative to the treatment and containment of this quickly evolving and frequently re-emerging disease. PMID:21858242

  14. Multiplex real-time RT-PCR for detecting chikungunya virus and dengue virus

    Institute of Scientific and Technical Information of China (English)

    Piyathida Pongsiri; Kesmanee Praianantathavorn; Apiradee Theamboonlers; Sunchai Payungporn; Yong Poovorawan

    2012-01-01

    ABSTRACT Objective:To develop diagnostic test for detection chikungunya virus (CHIKV and Dengue virus (DENV)infection.Methods:We have performed a rapid, accurate laboratory confirmative method to simultaneously detect, quantify and differentiateCHIKV and DENV infection by single-step multiplex real-timeRT-PCR.Results: The assay’s sensitivity was97.65%, specificity was 92.59% and accuracy was95.82% when compared to conventional RT-PCR. Additionally, there was no cross-reaction betweenCHIKV, DENV, Japanese encephalitis virus, hepatitis C, hepatitis A or hepatitis E virus.Conclusions:This rapid and reliable assay provides a means for simultaneous early diagnosis ofCHIKV andDENV in a single-step reaction.

  15. Early Events in Chikungunya Virus Infection—From Virus CellBinding to Membrane Fusion

    Directory of Open Access Journals (Sweden)

    Mareike K. S. van Duijl-Richter

    2015-07-01

    Full Text Available Chikungunya virus (CHIKV is a rapidly emerging mosquito-borne alphavirus causing millions of infections in the tropical and subtropical regions of the world. CHIKV infection often leads to an acute self-limited febrile illness with debilitating myalgia and arthralgia. A potential long-term complication of CHIKV infection is severe joint pain, which can last for months to years. There are no vaccines or specific therapeutics available to prevent or treat infection. This review describes the critical steps in CHIKV cell entry. We summarize the latest studies on the virus-cell tropism, virus-receptor binding, internalization, membrane fusion and review the molecules and compounds that have been described to interfere with virus cell entry. The aim of the review is to give the reader a state-of-the-art overview on CHIKV cell entry and to provide an outlook on potential new avenues in CHIKV research.

  16. Early Events in Chikungunya Virus Infection-From Virus Cell Binding to Membrane Fusion.

    Science.gov (United States)

    van Duijl-Richter, Mareike K S; Hoornweg, Tabitha E; Rodenhuis-Zybert, Izabela A; Smit, Jolanda M

    2015-07-07

    Chikungunya virus (CHIKV) is a rapidly emerging mosquito-borne alphavirus causing millions of infections in the tropical and subtropical regions of the world. CHIKV infection often leads to an acute self-limited febrile illness with debilitating myalgia and arthralgia. A potential long-term complication of CHIKV infection is severe joint pain, which can last for months to years. There are no vaccines or specific therapeutics available to prevent or treat infection. This review describes the critical steps in CHIKV cell entry. We summarize the latest studies on the virus-cell tropism, virus-receptor binding, internalization, membrane fusion and review the molecules and compounds that have been described to interfere with virus cell entry. The aim of the review is to give the reader a state-of-the-art overview on CHIKV cell entry and to provide an outlook on potential new avenues in CHIKV research.

  17. Aedes hensilli as a potential vector of Chikungunya and Zika viruses.

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    Jeremy P Ledermann

    2014-10-01

    Full Text Available An epidemic of Zika virus (ZIKV illness that occurred in July 2007 on Yap Island in the Federated States of Micronesia prompted entomological studies to identify both the primary vector(s involved in transmission and the ecological parameters contributing to the outbreak. Larval and pupal surveys were performed to identify the major containers serving as oviposition habitat for the likely vector(s. Adult mosquitoes were also collected by backpack aspiration, light trap, and gravid traps at select sites around the capital city. The predominant species found on the island was Aedes (Stegomyia hensilli. No virus isolates were obtained from the adult field material collected, nor did any of the immature mosquitoes that were allowed to emerge to adulthood contain viable virus or nucleic acid. Therefore, laboratory studies of the probable vector, Ae. hensilli, were undertaken to determine the likelihood of this species serving as a vector for Zika virus and other arboviruses. Infection rates of up to 86%, 62%, and 20% and dissemination rates of 23%, 80%, and 17% for Zika, chikungunya, and dengue-2 viruses respectively, were found supporting the possibility that this species served as a vector during the Zika outbreak and that it could play a role in transmitting other medically important arboviruses.

  18. First Complete Genome Sequence of a Chikungunya Virus Strain Isolated from a Patient Diagnosed with Dengue Virus Infection in Malaysia.

    Science.gov (United States)

    Ooi, Man Kwan; Gan, Han Ming; Rohani, Ahmad; Syed Hassan, Sharifah

    2016-01-01

    Here, we report the complete genome sequence of a chikungunya virus coinfection strain isolated from a dengue virus serotype 2-infected patient in Malaysia. This coinfection strain was determined to be of the Asian genotype and contains a novel insertion in the nsP3 gene. PMID:27563048

  19. First Complete Genome Sequence of a Chikungunya Virus Strain Isolated from a Patient Diagnosed with Dengue Virus Infection in Malaysia

    Science.gov (United States)

    Gan, Han Ming; Rohani, Ahmad

    2016-01-01

    Here, we report the complete genome sequence of a chikungunya virus coinfection strain isolated from a dengue virus serotype 2-infected patient in Malaysia. This coinfection strain was determined to be of the Asian genotype and contains a novel insertion in the nsP3 gene. PMID:27563048

  20. Induction of cytopathogenicity in human glioblastoma cells by chikungunya virus.

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    Rachy Abraham

    Full Text Available Chikungunya virus (CHIKV, an arthritogenic old-world alphavirus, has been implicated in the central nervous system (CNS infection in infants and elderly patients. Astrocytes are the major immune cells of the brain parenchyma that mediate inflammation. In the present study we found that a local isolate of CHIKV infect and activate U-87 MG cells, a glioblastoma cell line of human astrocyte origin. The infection kinetics were similar in infected U-87 MG cells and the human embryo kidney (HEK293 cells as indicated by immunofluorescence and plaque assays, 24h post-infection (p.i.. In infected U-87 MG cells, apoptosis was detectable from 48h p.i. evidenced by DNA fragmentation, PARP cleavage, loss of mitochondrial membrane potential, nuclear condensation and visible cytopathic effects in a dose and time-dependent manner. XBP1 mRNA splicing and eIF2α phosphorylation studies indicated the occurrence of endoplasmic reticulum stress in infected cells. In U-87 MG cells stably expressing a green fluorescent protein-tagged light chain-3 (GFP-LC3 protein, CHIKV infection showed increased autophagy response. The infection led to an enhanced expression of the mRNA transcripts of the pro-inflammatory cytokines IL-1β, TNF-α, IL-6 and CXCL9 within 24h p.i. Significant up-regulation of the proteins of RIG-I like receptor (RLR pathway, such as RIG-I and TRAF-6, was observed indicating the activation of the cytoplasmic-cellular innate immune response. The overall results show that the U-87 MG cell line is a potential in vitro model for in depth study of these molecular pathways in response to CHIKV infection. The responses in these cells of CNS origin, which are inherently defective in Type I interferon response, could be analogous to that occurring in infants and very old patients who also have a compromised interferon-response. The results also point to the intriguing possibility of using this virus for studies to develop oncolytic virus therapy approaches

  1. Nonhuman Primate Models of Chikungunya Virus Infection and Disease (CHIKV NHP Model)

    OpenAIRE

    Rebecca Broeckel; Nicole Haese; Ilhem Messaoudi; Streblow, Daniel N

    2015-01-01

    Chikungunya virus (CHIKV) is a positive-sense RNA virus transmitted by Aedes mosquitoes. CHIKV is a reemerging Alphavirus that causes acute febrile illness and severe and debilitating polyarthralgia of the peripheral joints. Huge epidemics and the rapid spread of CHIKV seen in India and the Indian Ocean region established CHIKV as a global health concern. This concern was further solidified by the recent incursion of the virus into the Western hemisphere, a region without pre-existing immunit...

  2. Evaluation of Commercially Available Chikungunya Virus Immunoglobulin M Detection Assays.

    Science.gov (United States)

    Johnson, Barbara W; Goodman, Christin H; Holloway, Kimberly; de Salazar, P Martinez; Valadere, Anne M; Drebot, Michael A

    2016-07-01

    Commercial chikungunya virus (CHIKV)-specific IgM detection kits were evaluated at the Centers for Disease Control and Prevention (CDC), the Public Health Agency of Canada National Microbiology Laboratory, and the Caribbean Public Health Agency (CARPHA). The Euroimmun Anti-CHIKV IgM ELISA kit had ≥ 95% concordance with all three reference laboratory results. The limit of detection for low CHIK IgM+ samples, as measured by serial dilution of seven sera up to 1:12,800 ranged from 1:800 to 1:3,200. The Euroimmun IIFT kit evaluated at CDC and CARPHA performed well, but required more retesting of equivocal results. The InBios CHIKjj Detect MAC-ELISA had 100% and 98% concordance with CDC and CARPHA results, respectively, and had equal sensitivity to the CDC MAC-ELISA to 1:12,800 dilution in serially diluted samples. The Abcam Anti-CHIKV IgM ELISA had high performance at CARPHA, but at CDC, performance was inconsistent between lots. After replacement of the biotinylated IgM antibody controls with serum containing CHIKV-specific IgM and additional quality assurance/control measures, the Abcam kit was rereleased and reevaluated at CDC. The reformatted Abcam kit had 97% concordance with CDC results and limit of detection of 1:800 to 1:3,200. Two rapid tests and three other CHIKV MAC-ELISAs evaluated at CDC had low sensitivity, as the CDC CHIKV IgM in-house positive controls were below the level of detection. In conclusion, laboratories have options for CHIKV serological diagnosis using validated commercial kits. PMID:26976887

  3. Congenital Chikungunya Virus Infection after an Outbreak in Salvador, Bahia, Brazil.

    Science.gov (United States)

    Lyra, Priscila Pinheiro Ribeiro; Campos, Gúbio Soares; Bandeira, Igor Dórea; Sardi, Silvia Ines; Costa, Lilian Ferreira de Moura; Santos, Flávia Rocha; Ribeiro, Carlos Alexandre Santos; Jardim, Alena Maria Barreto; Santiago, Ana Cecília Travassos; de Oliveira, Patrícia Maria Ribeiro; Moreira, Lícia Maria Oliveira

    2016-07-01

    There is little information about the congenital chikungunya virus (CHIKV) transmission. We describe two cases of well-documented congenital CHIKV infection in Salvador-Brazil, where CHIKV has been identified since 2014. The outbreak in the city led to the clinical CHIKV diagnoses of both pregnant women 2 days before delivery. Urine and blood samples from the mothers and newborns were collected and tested for reverse transcription-polymerase chain reaction (PCR) analysis for Zika, dengue, and CHIKV. Both neonates and mothers had positive urine and serum PCR results for CHIKV. The newborns had significant perinatal complications and were admitted to the neonatal intensive care unit. The purpose of our case report is to show how severe congenital CHIKV infection can be and the importance to include CHIKV infection in the differential diagnosis of neonatal sepsis when mothers have clinical signs of the disease and live in an affected area.

  4. Chikungunya Virus as Cause of Febrile Illness Outbreak, Chiapas, Mexico, 2014.

    Science.gov (United States)

    Kautz, Tiffany F; Díaz-González, Esteban E; Erasmus, Jesse H; Malo-García, Iliana R; Langsjoen, Rose M; Patterson, Edward I; Auguste, Dawn I; Forrester, Naomi L; Sanchez-Casas, Rosa Maria; Hernández-Ávila, Mauricio; Alpuche-Aranda, Celia M; Weaver, Scott C; Fernández-Salas, Ildefonso

    2015-11-01

    Since chikungunya virus (CHIKV) was introduced into the Americas in 2013, its geographic distribution has rapidly expanded. Of 119 serum samples collected in 2014 from febrile patients in southern Mexico, 79% were positive for CHIKV or IgM against CHIKV. Sequencing results confirmed CHIKV strains closely related to Caribbean isolates. PMID:26488312

  5. Functional processing and secretion of Chikungunya virus E1 and E2 glycoproteins in insect cells

    NARCIS (Netherlands)

    S.W. Metz (Stefan); C. Geertsema (Corinne); B.E.E. Martina (Byron); P. Andrade (Paulina); J.G.M. Heldens; M.M. van Oers (Monique); J.M. Vlak (Just); G.P. Pijlman (Gorben)

    2011-01-01

    textabstractBackground: Chikungunya virus (CHIKV) is a mosquito-borne, arthrogenic Alphavirus that causes large epidemics in Africa, South-East Asia and India. Recently, CHIKV has been transmitted to humans in Southern Europe by invading and now established Asian tiger mosquitoes. To study the proce

  6. Detection of east/central/south African genotype of chikungunya virus in Myanmar, 2010.

    Science.gov (United States)

    Tun, Mya Myat Ngwe; Thant, Kyaw Zin; Inoue, Shingo; Nabeshima, Takeshi; Aoki, Kotaro; Kyaw, Aung Kyaw; Myint, Tin; Tar, Thi; Maung, Kay Thwe Thwe; Hayasaka, Daisuke; Morita, Kouichi

    2014-08-01

    In 2010, chikungunya virus of the East Central South African genotype was isolated from 4 children in Myanmyar who had dengue-like symptoms. Phylogenetic analysis of the E1 gene revealed that the isolates were closely related to isolates from China, Thailand, and Malaysia that harbor the A226V mutation in this gene.

  7. Chikungunya virus infection: report of the first case diagnosed in Rio de Janeiro, Brazil

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    Isabella Gomes Cavalcanti de Albuquerque

    2012-02-01

    Full Text Available Initially diagnosed in Africa and Asia, the Chikungunya virus has been detected in the last three years in the Caribbean, Italy, France, and the United States of America. Herein, we report the first case for Rio de Janeiro, Brazil, in 2010.

  8. Isolation and diagnosis of Chikungunya virus causing outbreaks in Andhra Pradesh, India

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    C.V.M. Naresh Kumar

    2013-01-01

    Full Text Available Background: Chikungunya fever has recently re-emerged in India with a high morbidity. However, the prevalence of chikungunya fever in India has been underreported due to non-availability of specialized kits to confirm the disease in most of the laboratories. Methods: Nine hundred and fifty six serum samples were collected from subjects presenting with a short febrile illness from various places in Chittoor district, Andhra Pradesh, between January to October 2009 and were screened for Chikungunya Virus (CHIKV infection. Virus isolation, reverse transcriptase - polymerase chain reaction (RT-PCR and immunoglobulin M (IgM rapid strip method were employed for the identification of the causative agent. Results: Chikungunya Virus (CHIKV infection was confirmed in 520 (68.1% patients by RT-PCR. Seventy seven (40.1% patients showed the presence of anti-CHIKV IgM antibodies while 12 (6.3% patients showed the presence of both anti-CHIKV IgM and immunoglobulin G (IgG antibodies respectively. The isolation of CHIKV was successful from five patients. Conclusions: The re-emergence and persistence of CHIKV in Andhra Pradesh suggests the need for continuous monitoring and identification of the pathogen and thereby prevention of the spread of the virus to other parts of the country.

  9. Genomic Assays for Identification of Chikungunya Virus in Blood Donors, Puerto Rico, 2014.

    Science.gov (United States)

    Chiu, Charles Y; Bres, Vanessa; Yu, Guixia; Krysztof, David; Naccache, Samia N; Lee, Deanna; Pfeil, Jacob; Linnen, Jeffrey M; Stramer, Susan L

    2015-08-01

    A newly developed transcription-mediated amplification assay was used to detect chikungunya virus infection in 3 of 557 asymptomatic donors (0.54%) from Puerto Rico during the 2014-2015 Caribbean epidemic. Viral detection was confirmed by using PCR, microarray, and next-generation sequencing. Molecular clock analysis dated the emergence of the Puerto Rico strains to early 2013.

  10. Development of a Highly Protective Combination Monoclonal Antibody Therapy against Chikungunya Virus

    NARCIS (Netherlands)

    Pal, Pankaj; Dowd, Kimberly A.; Brien, James D.; Edeling, Melissa A.; Gorlatov, Sergey; Johnson, Syd; Lee, Iris; Akahata, Wataru; Nabel, Gary J.; Richter, Mareike K. S.; Smit, Jolanda M.; Fremont, Daved H.; Pierson, Theodore C.; Heise, Mark T.; Diamond, Michael S.

    2013-01-01

    Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that causes global epidemics of a debilitating polyarthritis in humans. As there is a pressing need for the development of therapeutic agents, we screened 230 new mouse anti-CHIKV monoclonal antibodies (MAbs) for their ability to inhibit

  11. Functional processing and secretion of Chikungunya virus E1 and E2 glycoproteins in insect cells

    NARCIS (Netherlands)

    Metz, S.W.H.; Geertsema, C.; Martina, Byron E.; Andrade, Paulina; Heldens, J.; Oers, van M.M.; Goldbach, R.W.; Vlak, J.M.; Pijlman, G.P.

    2011-01-01

    Background - Chikungunya virus (CHIKV) is a mosquito-borne, arthrogenic Alphavirus that causes large epidemics in Africa, South-East Asia and India. Recently, CHIKV has been transmitted to humans in Southern Europe by invading and now established Asian tiger mosquitoes. To study the processing of en

  12. Chikungunya virus fusion properties elucidated by single-particle and bulk approaches

    NARCIS (Netherlands)

    van Duijl-Richter, Mareike K. S.; Blijleven, Jelle S.; van Oijen, Antoine M.; Smit, Jolanda M.

    2015-01-01

    Chikungunya virus (CHIKV) is a rapidly spreading, enveloped alphavirus causing fever, rash and debilitating polyarthritis. No specific treatment or vaccines are available to treat or prevent infection. For the rational design of vaccines and antiviral drugs, it is imperative to understand the molecu

  13. Detection of East/Central/South African Genotype of Chikungunya Virus in Myanmar, 2010

    OpenAIRE

    Tun, Mya Myat Ngwe; Thant, Kyaw Zin; Inoue, Shingo; Nabeshima, Takeshi; Aoki, Kotaro; Kyaw, Aung Kyaw; Myint, Tin; Tar, Thi; Maung, Kay Thwe Thwe; Hayasaka, Daisuke; Morita, Kouichi

    2014-01-01

    In 2010, chikungunya virus of the East Central South African genotype was isolated from 4 children in Myanmyar who had dengue-like symptoms. Phylogenetic analysis of the E1 gene revealed that the isolates were closely related to isolates from China, Thailand, and Malaysia that harbor the A226V mutation in this gene.

  14. Genetic divergence of Chikungunya virus plaque variants from the Comoros Island (2005).

    Science.gov (United States)

    Wasonga, Caroline; Inoue, Shingo; Rumberia, Cecilia; Michuki, George; Kimotho, James; Ongus, Juliette R; Sang, Rosemary; Musila, Lillian

    2015-12-01

    Chikungunya virus (CHIKV) from a human sample collected during the 2005 Chikungunya outbreak in the Comoros Island, showed distinct and reproducible large (L2) and small (S7) plaques which were characterized in this study. The parent strain and plaque variants were analysed by in vitro growth kinetics in different cell lines and their genetic similarity assessed by whole genome sequencing, comparative sequence alignment and phylogenetic analysis. In vitro growth kinetic assays showed similar growth patterns of both plaque variants in Vero cells but higher viral titres of S7 compared to L2 in C6/36 cells. Amino acids (AA) alignments of the CHIKV plaque variants and S27 African prototype strain, showed 30 AA changes in the non-structural proteins (nsP) and 22 AA changes in the structural proteins. Between L2 and S7, only two AAs differences were observed. A missense substitution (C642Y) of L2 in the nsP2, involving a conservative AA substitution and a nonsense substitution (R524X) of S7 in the nsP3, which has been shown to enhance O'nyong-nyong virus infectivity and dissemination in Anopheles mosquitoes. The phenotypic difference observed in plaque size could be attributed to one of these AA substitutions. Phylogenetic analysis showed that the parent strain and its variants clustered closely together with each other and with Indian Ocean CHIKV strains indicating circulation of isolates with close evolutionary relatedness in the same outbreak. These observations pave way for important functional studies to understand the significance of the identified genetic changes in virulence and viral transmission in mosquito and mammalian hosts.

  15. Effective cutaneous vaccination using an inactivated chikungunya virus vaccine delivered by Foroderm.

    Science.gov (United States)

    Rudd, Penny A; Raphael, Anthony P; Yamada, Miko; Nufer, Kaitlin L; Gardner, Joy; Le, Thuy T T; Prow, Natalie A; Dang, Nhung; Schroder, Wayne A; Prow, Tarl W; Suhrbier, Andreas

    2015-09-22

    Foroderm is a new cutaneous delivery technology that uses high-aspect ratio, cylindrical silica microparticles, that are massaged into the skin using a 3D-printed microtextured applicator, in order to deliver payloads across the epidermis. Herein we show that this technology is effective for delivery of a non-adjuvanted, inactivated, whole-virus chikungunya virus vaccine in mice, with minimal post-vaccination skin reactions. A single topical Foroderm-based vaccination induced T cell, Th1 cytokine and antibody responses, which provided complete protection against viraemia and disease after challenge with chikungunya virus. Foroderm vaccination was shown to deliver fluorescent, virus-sized beads across the epidermis, with beads subsequently detected in draining lymph nodes. Foroderm vaccination also stimulated the egress of MHC II(+) antigen presenting cells from the skin. Foroderm thus has potential as a simple, cheap, effective, generic, needle-free technology for topical delivery of vaccines.

  16. Chikungunya virus RNA and antibody testing at a National Reference Laboratory since the emergence of Chikungunya virus in the Americas.

    Science.gov (United States)

    Prince, Harry E; Seaton, Brent L; Matud, Jose L; Batterman, Hollis J

    2015-03-01

    Since first reported in the Americas in December 2013, chikungunya virus (CHIKV) infections have been documented in travelers returning from the Caribbean, with many cases identified by CHIKV antibody and/or RNA testing at our laboratory. We used our large data set to characterize the relationship between antibody titers and RNA detection and to estimate IgM persistence. CHIKV RNA was measured by nucleic acid amplification and CHIKV IgG/IgM by indirect immunofluorescence. Of the 1,306 samples submitted for RNA testing in January through September 2014, 393 (30%) were positive; for 166 RNA-positive samples, CHIKV antibody testing was also ordered, and 84% were antibody negative. Of the 6,971 sera submitted for antibody testing in January through September 2014, 1,811 (26%) were IgM positive; 1,461 IgM positives (81%) were also IgG positive. The relationship between the CHIKV antibody titers and RNA detection was evaluated using 376 IgM-positive samples (138 with RNA testing ordered and 238 deidentified and tested for RNA). RNA detection showed no significant association with the IgM titer but was inversely related to the IgG titer; 63% of the IgG negative sera were RNA positive, compared to 36% of sera with low IgG titers (1:10 to 1:80) and 16% with IgG titers of ≥1:160. Using second-sample results from 62 seroconverters, we estimated that CHIKV IgM persists for 110 days (95% confidence interval, 78 to 150 days) after the initial antibody-negative sample. These findings indicate that (i) RNA detection is more sensitive than antibody detection early in CHIKV infection, (ii) in the absence of RNA results, the IgG titer of the IgM-positive samples may be a useful surrogate for viremia, and (iii) CHIKV IgM persists for approximately 4 months after symptom onset.

  17. Recombinant Modified Vaccinia Virus Ankara Expressing Glycoprotein E2 of Chikungunya Virus Protects AG129 Mice against Lethal Challenge

    NARCIS (Netherlands)

    P. van den Doel (Petra); A. Volz (Asisa); J.M. Roose (Jouke M.); V.D. Sewbalaksing (Varsha); G.P. Pijlman (Gorben); I. van Middelkoop (Ingeborg); V. Duiverman (Vincent); E. van de Wetering (Eva); G. Sutter (Gerd); A.D.M.E. Osterhaus (Albert); B.E.E. Martina (Byron)

    2014-01-01

    textabstractChikungunya virus (CHIKV) infection is characterized by rash, acute high fever, chills, headache, nausea, photophobia, vomiting, and severe polyarthralgia. There is evidence that arthralgia can persist for years and result in long-term discomfort. Neurologic disease with fatal outcome ha

  18. Recombinant modified vaccinia virus Ankara expressing glycoprotein E2 of Chikungunya virus protects AG129 mice against lethal challenge

    NARCIS (Netherlands)

    Doel, van den P.; Volz, A.; Roose, J.M.; Sewbalaksing, V.D.; Pijlman, G.P.; Middelkoop, van I.; Duiverman, V.; Wetering, van de E.; Sutter, G.; Osterhaus, A.D.; Martina, B.E.

    2014-01-01

    Chikungunya virus (CHIKV) infection is characterized by rash, acute high fever, chills, headache, nausea, photophobia, vomiting, and severe polyarthralgia. There is evidence that arthralgia can persist for years and result in long-term discomfort. Neurologic disease with fatal outcome has been docum

  19. Molecular epidemiology, evolution and phylogeny of Chikungunya virus: An updating review.

    Science.gov (United States)

    Lo Presti, Alessandra; Cella, Eleonora; Angeletti, Silvia; Ciccozzi, Massimo

    2016-07-01

    Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus belonging to the Togaviridae family, causing a febrile illness associated with severe arthralgia and rash. In this review, we summarized a series of articles published from 2013 to 2016 concerning CHIKV epidemiology, phylogeny, vaccine and therapies, to give an update of our most recent article written in 2014 (Lo Presti et al.,2014). CHIKV infection was first reported in 1952 from Makonde plateaus and since this time caused many outbreaks worldwide, involving the Indian Ocean region, African countries, American continent and Italy. CHIKV infection is still underestimated and it is normally associated with clinical symptoms overlapping with dengue virus, recurring epidemics and mutations within the viral genome. These characteristics promote the geographical spread and the inability to control vector-mediated transmission of the virus. For these reasons, the majority of studies were aimed to describe outbreaks and to enhance knowledge on CHIKV biology, pathogenesis, infection treatment, and prevention. In this review, 16 studies on CHIKV phylogenetic and phylodinamics were considered, during the years 2013-2016. Phylogenetic and phylodinamic analysis are useful tools to investigate how the genealogy of a pathogen population is influenced by pathogen's demographic history, host immunological milieu and environmental/ecological factors. Phylogenetic tools were revealed important to reconstruct the geographic spread of CHIKV during the epidemics wave and to have information on the circulating strains of the virus, that are important for the prediction and control of the epidemics, as well as for vaccines and antiviral drugs development. In conclusion, this updating review can give a critical appraisal of the epidemiology, therapeutic and phylogenesis of CHIKV, reinforcing the need to monitor the geographic spread of virus and vectors. PMID:27085290

  20. Utilization and Assessment of Throat Swab and Urine Specimens for Diagnosis of Chikungunya Virus Infection.

    Science.gov (United States)

    Raut, Chandrashekhar G; Hanumaiah, H; Raut, Wrunda C

    2016-01-01

    Chikungunya is a mosquito-borne infection with clinical presentation of fever, arthralgia, and rash. The etiological agent Chikungunya virus (CHIKV) is generally transmitted from primates to humans through the bites of infected Aedes aegypti and Aedes albopictus mosquitoes. Outbreaks of Chikungunya occur commonly with varied morbidity, mortality, and sequele according to the epidemiological, ecological, seasonal, and geographical impact. Investigations are required to be conducted as a part of the public health service to understand and report the suspected cases as confirmed by laboratory diagnosis. Holistic sampling at a time of different types would be useful for laboratory testing, result conclusion, and reporting in a valid way. The use of serum samples for virus detection, virus isolation, and serology is routinely practiced, but sometimes serum samples from pediatric and other cases may not be easily available. In such a situation, easily available throat swabs and urine samples could be useful. It is already well reported for measles, rubella, and mumps diseases to have the virus diagnosis from throat swabs and urine. Here, we present the protocols for diagnosis of CHIKV using throat swab and urine specimens. PMID:27233262

  1. Evidence of experimental vertical transmission of emerging novel ECSA genotype of Chikungunya Virus in Aedes aegypti.

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    Ankita Agarwal

    Full Text Available BACKGROUND: Chikungunya virus (CHIKV has emerged as one of the most important arboviruses of public health significance in the past decade. The virus is mainly maintained through human-mosquito-human cycle. Other routes of transmission and the mechanism of maintenance of the virus in nature are not clearly known. Vertical transmission may be a mechanism of sustaining the virus during inter-epidemic periods. Laboratory experiments were conducted to determine whether Aedes aegypti, a principal vector, is capable of vertically transmitting CHIKV or not. METHODOLOGY/PRINCIPAL FINDINGS: Female Ae. aegypti were orally infected with a novel ECSA genotype of CHIKV in the 2nd gonotrophic cycle. On day 10 post infection, a non-infectious blood meal was provided to obtain another cycle of eggs. Larvae and adults developed from the eggs obtained following both infectious and non-infectious blood meal were tested for the presence of CHIKV specific RNA through real time RT-PCR. The results revealed that the larvae and adults developed from eggs derived from the infectious blood meal (2nd gonotrophic cycle were negative for CHIKV RNA. However, the larvae and adults developed after subsequent non-infectious blood meal (3rd gonotrophic cycle were positive with minimum filial infection rates of 28.2 (1∶35.5 and 20.2 (1∶49.5 respectively. CONCLUSION/SIGNIFICANCE: This study is the first to confirm experimental vertical transmission of emerging novel ECSA genotype of CHIKV in Ae. aegypti from India, indicating the possibilities of occurrence of this phenomenon in nature. This evidence may have important consequence for survival of CHIKV during adverse climatic conditions and inter-epidemic periods.

  2. Genetic characterization of 2006-2008 isolates of Chikungunya virus from Kerala, South India, by whole genome sequence analysis.

    Science.gov (United States)

    Sreekumar, E; Issac, Aneesh; Nair, Sajith; Hariharan, Ramkumar; Janki, M B; Arathy, D S; Regu, R; Mathew, Thomas; Anoop, M; Niyas, K P; Pillai, M R

    2010-02-01

    Chikungunya virus (CHIKV), a positive-stranded alphavirus, causes epidemic febrile infections characterized by severe and prolonged arthralgia. In the present study, six CHIKV isolates (2006 RGCB03, RGCB05; 2007 RGCB80, RGCB120; 2008 RGCB355, RGCB356) from three consecutive Chikungunya outbreaks in Kerala, South India, were analyzed for genetic variations by sequencing the 11798 bp whole genome of the virus. A total of 37 novel mutations were identified and they were predominant in the 2007 and 2008 isolates among the six isolates studied. The previously identified E1 A226V critical mutation, which enhances mosquito adaptability, was present in the 2007 and 2008 samples. An important observation was the presence of two coding region substitutions, leading to nsP2 L539S and E2 K252Q change. These were identified in three isolates (2007 RGCB80 and RGCB120; 2008 RGCB355) by full-genome analysis, and also in 13 of the 31 additional samples (42%), obtained from various parts of the state, by sequencing the corresponding genomic regions. These mutations showed 100% co-occurrence in all these samples. In phylogenetic analysis, formation of a new genetic clade by these isolates within the East, Central and South African (ECSA) genotypes was observed. Homology modeling followed by mapping revealed that at least 20 of the identified mutations fall into functionally significant domains of the viral proteins and are predicted to affect protein structure. Eighteen of the identified mutations in structural proteins, including the E2 K252Q change, are predicted to disrupt T-cell epitope immunogenicity. Our study reveals that CHIK virus with novel genetic changes were present in the severe Chikungunya outbreaks in 2007 and 2008 in South India. PMID:19851853

  3. A226V mutation in virus during the 2007 chikungunya outbreak in Kerala, India.

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    Kumar, N Pradeep; Joseph, Rajan; Kamaraj, T; Jambulingam, P

    2008-08-01

    Kerala State in India was gripped by a renewed and widespread outbreak of Chikungunya virus (CHIKV) infection during 2007. Here, we report the A226V mutation in the glycoprotein envelope 1 (E1) gene of the virus among isolates collected from the three worst-affected districts of the state during this outbreak. This mutation had already been suggested to be directly responsible for a significant increase in CHIKV infectivity in Aedes albopictus. The badly affected districts in Kerala State during 2007 have abundant rubber plantations, which supported prolific breeding of Ae. albopictus mosquitoes. The abundance of Ae. albopictus in the region and molecular evolution of CHIKV may be contributing factors for the renewed epidemic of chikungunya fever during 2007. PMID:18632966

  4. Tigliane diterpenes from Croton mauritianus as inhibitors of chikungunya virus replication.

    Science.gov (United States)

    Corlay, Nina; Delang, Leen; Girard-Valenciennes, Emmanuelle; Neyts, Johan; Clerc, Patricia; Smadja, Jacqueline; Guéritte, Françoise; Leyssen, Pieter; Litaudon, Marc

    2014-09-01

    A bioassay-guided purification of an EtOAc extract of the leaves of Croton mauritianus using a chikungunya virus-cell-based assay led to the isolation of 12-O-decanoylphorbol-13-acetate (1) and the new 12-O-decanoyl-7-hydroperoxy-phorbol-5-ene-13-acetate (2), along with loliolide, vomifoliol, dehydrovomifoliol, annuionone D and bluemol C. The planar structure and the relative configuration of compound 2 were elucidated based on spectroscopic analysis, including 1D- and 2D-NMR experiments, mass spectrometry, and comparison with literature data. Compounds 1 and 2 inhibited chikungunya virus-induced cell death in cell culture with EC50s of 2.4±0.3 and 4.0±0.8 μM, respectively. PMID:24879904

  5. Tigliane diterpenes from Croton mauritianus as inhibitors of chikungunya virus replication.

    Science.gov (United States)

    Corlay, Nina; Delang, Leen; Girard-Valenciennes, Emmanuelle; Neyts, Johan; Clerc, Patricia; Smadja, Jacqueline; Guéritte, Françoise; Leyssen, Pieter; Litaudon, Marc

    2014-09-01

    A bioassay-guided purification of an EtOAc extract of the leaves of Croton mauritianus using a chikungunya virus-cell-based assay led to the isolation of 12-O-decanoylphorbol-13-acetate (1) and the new 12-O-decanoyl-7-hydroperoxy-phorbol-5-ene-13-acetate (2), along with loliolide, vomifoliol, dehydrovomifoliol, annuionone D and bluemol C. The planar structure and the relative configuration of compound 2 were elucidated based on spectroscopic analysis, including 1D- and 2D-NMR experiments, mass spectrometry, and comparison with literature data. Compounds 1 and 2 inhibited chikungunya virus-induced cell death in cell culture with EC50s of 2.4±0.3 and 4.0±0.8 μM, respectively.

  6. Development and evaluation of baculovirus-expressed Chikungunya virus E1 envelope proteins for serodiagnosis of Chikungunya infection.

    Science.gov (United States)

    Kumar, Pankaj; Pok, Kwoon-Yong; Tan, Li-Kiang; Angela, Chow; Leo, Yee-Sin; Ng, Lee-Ching

    2014-09-01

    Population-based serosurveillance studies provide critical estimates on community-level immunity and the potential for future outbreaks. Currently, serological assays, such as IgG enzyme-linked immunosorbent assays (ELISAs) and indirect immunofluorescence tests (IIFT) based on the inactivated whole virus are used to determine past Chikungunya virus (CHIKV) infection. However, these commercially available tests have variable sensitivities. To develop and evaluate recombinant based CHIKV-specific IgG antibody capture ELISAs (GAC-ELISAs), baculoviruses carrying wild-type (E1-A226, named WT) or mutant (E1-A226V, named MUT) E1 envelope protein genes of CHIKV were generated. The seroreactivity of recombinant CHIKV WT and MUT envelope proteins were determined using residual blood, collected from CHIKV-confirmed patients. The sensitivities of both recombinant CHIKV envelope proteins were 83.0% as measured by GAC-ELISAs. The specificities of both recombinant proteins were 87.8%. These GAC-ELISAs were also able to detect the persistence of anti-CHIKV IgG antibodies up to 6 months after the disease onset, together with rise in sensitivities with increasing time. These results suggest that the baculovirus purified recombinant CHIKV envelope proteins react with anti-CHIKV IgG antibodies and may be useful in population-based seroprevalence surveys. In addition, these GAC-ELISAs offer good diagnostic value to determine the recent/past CHIKV infection status in non-endemic populations.

  7. Impact of chikungunya virus infection on oral health status: An observational study

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    Roopa Katti

    2011-01-01

    Full Text Available Background and Objective: Chikungunya fever outbreak started in December 2005 in India when the country experienced more than 13 lakhs of Chikungunya infected cases. We undertook this study to describe the impact of Chikungunya virus infection on oral health. Materials and Methods: The confirmed seropositive patients were included for the study (N = 97. Oral hygiene index simplified, gingival index, plaque index were recorded. Results: Of the 181 tested, 97 were confirmed seropositive for chikungunya infection. Pain and bleeding gums were seen in 55% of the subjects. Of them, 29.1% had poor oral hygiene, 42.27% had severe gingivitis, and 27.84% had severe plaque deposits. Severe gingivitis was observed in patients with chronic disease, this association was statistically significant (χ2 = 6.417, P = 0.040. Conclusion: Our findings showed that about more than half of the tested patients suffered severe pain and bleeding in the oral cavity thereby causing discomfort in chewing. About 1/3 patients had severe gingivitis and foul breath which caused discomfort in carrying out their day-to-day activities.

  8. Chikungunya Virus Replication in Salivary Glands of the Mosquito Aedes albopictus

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    Anubis Vega-Rúa

    2015-11-01

    Full Text Available Chikungunya virus (CHIKV is an emerging arbovirus transmitted to humans by mosquitoes such as Aedes albopictus. To be transmitted, CHIKV must replicate in the mosquito midgut, then disseminate in the hemocele and infect the salivary glands before being released in saliva. We have developed a standardized protocol to visualize viral particles in the mosquito salivary glands using transmission electron microscopy. Here we provide direct evidence for CHIKV replication and storage in Ae. albopictus salivary glands.

  9. Chikungunya Virus Replication in Salivary Glands of the Mosquito Aedes albopictus.

    Science.gov (United States)

    Vega-Rúa, Anubis; Schmitt, Christine; Bonne, Isabelle; Krijnse Locker, Jacomine; Failloux, Anna-Bella

    2015-11-17

    Chikungunya virus (CHIKV) is an emerging arbovirus transmitted to humans by mosquitoes such as Aedes albopictus. To be transmitted, CHIKV must replicate in the mosquito midgut, then disseminate in the hemocele and infect the salivary glands before being released in saliva. We have developed a standardized protocol to visualize viral particles in the mosquito salivary glands using transmission electron microscopy. Here we provide direct evidence for CHIKV replication and storage in Ae. albopictus salivary glands.

  10. Cases of chikungunya virus infection in travellers returning to Spain from Haiti or Dominican Republic, April-June 2014.

    Science.gov (United States)

    Requena-Méndez, A; Garcia, C; Aldasoro, E; Vicente, J A; Martínez, M J; Pérez-Molina, J A; Calvo-Cano, A; Franco, L; Parrón, I; Molina, A; Ruiz, M; Álvarez, J; Sánchez-Seco, M P; Gascón, J

    2014-01-01

    Ten cases of chikungunya were diagnosed in Spanish travellers returning from Haiti (n=2), the Dominican Republic (n=7) or from both countries (n=1) between April and June 2014. These cases remind clinicians to consider chikungunya in European travellers presenting with febrile illness and arthralgia, who are returning from the Caribbean region and Central America, particularly from Haiti and the Dominican Republic. The presence of Aedes albopictus together with viraemic patients could potentially lead to autochthonous transmission of chikungunya virus in southern Europe.

  11. Chikungunya virus infections among travellers returning to Spain, 2008 to 2014

    Science.gov (United States)

    Fernandez-Garcia, Maria Dolores; Bangert, Mathieu; de Ory, Fernando; Potente, Arantxa; Hernandez, Lourdes; Lasala, Fatima; Herrero, Laura; Molero, Francisca; Negredo, Anabel; Vázquez, Ana; Minguito, Teodora; Balfagón, Pilar; de la Fuente, Jesus; Puente, Sabino; Ramírez de Arellano, Eva; Lago, Mar; Martinez, Miguel; Gascón, Joaquim; Norman, Francesca; Lopez-Velez, Rogelio; Sulleiro, Elena; Pou, Diana; Serre, Nuria; Roblas, Ricardo Fernández; Tenorio, Antonio; Franco, Leticia; Sanchez-Seco, Maria Paz

    2016-01-01

    Since the first documented autochthonous transmission of chikungunya virus in the Caribbean island of Saint Martin in 2013, the infection has been reported within the Caribbean region as well as North, Central and South America. The risk of autochthonous transmission of chikungunya virus becoming established in Spain may be elevated due to the large numbers of travellers returning to Spain from countries affected by the 2013 epidemic in the Caribbean and South America, as well as the existence of the Aedes albopictus vector in certain parts of Spain. We retrospectively analysed the laboratory diagnostic database of the National Centre for Microbiology, Institute of Health Carlos III (CNM-ISCIII) from 2008 to 2014. During the study period, 264 confirmed cases, of 1,371 suspected cases, were diagnosed at the CNM-ISCIII. In 2014 alone, there were 234 confirmed cases. The highest number of confirmed cases were reported from the Dominican Republic (n = 136), Venezuela (n = 30) and Haiti (n = 11). Six cases were viraemic in areas of Spain where the vector is present. This report highlights the need for integrated active case and vector surveillance in Spain and other parts of Europe where chikungunya virus may be introduced by returning travellers. PMID:27631156

  12. Chikungunya Virus & Chikungunya Fever%基孔肯雅病毒与基孔肯雅热

    Institute of Scientific and Technical Information of China (English)

    邵惠训

    2011-01-01

    基孔肯雅热是一种人兽共患病,是由基孔肯雅病毒(chikungunya virus,CHIKV)引起,以发热、皮疹、关节疼痛和轻度出血为主要特征的急性传染病.这种病毒病主要分布在非洲、南亚、东南亚热带和亚热带地区.近年来在印度洋地区造成大规模流行,并波及我国南方,疫区在不断扩大.埃及伊蚊和白纹伊蚊是主要传播媒介.通过携带病毒的伊蚊叮咬而传播.在实验室内可通过气溶胶传播,目前尚无直接人传人的报道.多数病人能完全痊愈,但有些病人关节疼痛持续较长时间.

  13. Chikungunya virus infection amongst the acute encephalitis syndrome cases in West Bengal, India

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    D Taraphdar

    2015-01-01

    Full Text Available Chikungunya virus (CHIKV infection from the acute encephalitis syndrome cases is an uncommon form and has been observed in the year 2010-11 from West Bengal, India. The case-1 and case-2 had the acute encephalitis syndrome; case-3 was of acute disseminated encephalomyelitis whereas the case-4 had the symptoms of meningo-encephalopathy with bulbar involvement. We are reporting four cases with neurological complications involving central nervous system (CNS due to CHIKV infection from this state for the first time. The virus has spread almost every districts of this state rapidly. At this stage, these cases are public health threat.

  14. Structure based design towards the identification of novel binding sites and inhibitors for the chikungunya virus envelope proteins.

    Science.gov (United States)

    Rashad, Adel A; Keller, Paul A

    2013-07-01

    Chikungunya virus is an emerging arbovirus that is widespread in tropical regions and is spreading quickly to temperate climates with recent epidemics in Africa, Asia, Europe and the Americas. It is having an increasingly major impact on humans with potentially life-threatening and debilitating arthritis. Thus far, neither vaccines nor medications are available to treat or control the virus and therefore, the development of medicinal chemistry is a vital and immediate issue that needs to be addressed. The viral envelope proteins play a major role during infection through mediation of binding and fusion with the infected cell surfaces. The possible binding target sites of the chikungunya virus envelope proteins have not previously been investigated; we describe here for the first time the identification of novel sites for potential binding on the chikungunya glycoprotein complexes and the identification of possible antagonists for these sites through virtual screening using two successive docking scores; FRED docking for fast precise screening, with the top hits then subjected to a ranking scoring using the AUTODOCK algorithm. Both the immature and the mature forms of the chikungunya envelope proteins were included in the study to increase the probability of finding positive and reliable hits. Some small molecules have been identified as good in silico chikungunya virus envelope proteins inhibitors and these could be good templates for drug design targeting this virus.

  15. First Report of Aedes aegypti Transmission of Chikungunya Virus in the Americas.

    Science.gov (United States)

    Díaz-González, Esteban E; Kautz, Tiffany F; Dorantes-Delgado, Alicia; Malo-García, Iliana R; Laguna-Aguilar, Maricela; Langsjoen, Rose M; Chen, Rubing; Auguste, Dawn I; Sánchez-Casas, Rosa M; Danis-Lozano, Rogelio; Weaver, Scott C; Fernández-Salas, Ildefonso

    2015-12-01

    During a chikungunya fever outbreak in late 2014 in Chiapas, Mexico, entomovirological surveillance was performed to incriminate the vector(s). In neighborhoods, 75 households with suspected cases were sampled for mosquitoes, of which 80% (60) harbored Aedes aegypti and 2.7% (2) Aedes albopictus. A total of 1,170 Ae. aegypti and three Ae. albopictus was collected and 81 pools were generated. Although none of the Ae. albopictus pools were chikungunya virus (CHIKV)-positive, 18 Ae. aegypti pools (22.8%) contained CHIKV, yielding an infection rate of 32.3/1,000 mosquitoes. A lack of herd immunity in conjunction with high mosquito populations, poor vector control services in this region, and targeted collections in locations of human cases may explain the high infection rate in this vector. Consistent with predictions from experimental studies, Ae. aegypti appears to be the principal vector of CHIKV in southern Mexico, while the role of Ae. albopictus remains unknown. PMID:26416113

  16. Interferon-Induced Spermidine-Spermine Acetyltransferase and Polyamine Depletion Restrict Zika and Chikungunya Viruses.

    Science.gov (United States)

    Mounce, Bryan C; Poirier, Enzo Z; Passoni, Gabriella; Simon-Loriere, Etienne; Cesaro, Teresa; Prot, Matthieu; Stapleford, Kenneth A; Moratorio, Gonzalo; Sakuntabhai, Anavaj; Levraud, Jean-Pierre; Vignuzzi, Marco

    2016-08-10

    Polyamines are small, positively charged molecules derived from ornithine and synthesized through an intricately regulated enzymatic pathway. Within cells, they are abundant and play several roles in diverse processes. We find that polyamines are required for the life cycle of the RNA viruses chikungunya virus (CHIKV) and Zika virus (ZIKV). Depletion of spermidine and spermine via type I interferon signaling-mediated induction of spermidine/spermine N1-acetyltransferase (SAT1), a key catabolic enzyme in the polyamine pathway, restricts CHIKV and ZIKV replication. Polyamine depletion restricts these viruses in vitro and in vivo, due to impairment of viral translation and RNA replication. The restriction is released by exogenous replenishment of polyamines, further supporting a role for these molecules in virus replication. Thus, SAT1 and, more broadly, polyamine depletion restrict viral replication and suggest promising avenues for antiviral therapies. PMID:27427208

  17. Real-time whole-body visualization of Chikungunya Virus infection and host interferon response in zebrafish.

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    Nuno Palha

    Full Text Available Chikungunya Virus (CHIKV, a re-emerging arbovirus that may cause severe disease, constitutes an important public health problem. Herein we describe a novel CHIKV infection model in zebrafish, where viral spread was live-imaged in the whole body up to cellular resolution. Infected cells emerged in various organs in one principal wave with a median appearance time of ∼14 hours post infection. Timing of infected cell death was organ dependent, leading to a shift of CHIKV localization towards the brain. As in mammals, CHIKV infection triggered a strong type-I interferon (IFN response, critical for survival. IFN was mainly expressed by neutrophils and hepatocytes. Cell type specific ablation experiments further demonstrated that neutrophils play a crucial, unexpected role in CHIKV containment. Altogether, our results show that the zebrafish represents a novel valuable model to dynamically visualize replication, pathogenesis and host responses to a human virus.

  18. Zika Virus Emergence and Expansion: Lessons Learned from Dengue and Chikungunya May Not Provide All the Answers.

    Science.gov (United States)

    Christofferson, Rebecca C

    2016-07-01

    Following the emergence of Zika in the past decade, there are lessons to be learned from similar emergence events of dengue (DENV) and chikungunya (CHIKV). Specifically, as Zika emerges in the Americas there is a natural tendency to apply the knowledge base of DENV and CHIKV to mitigation and control of a virus with such a similar transmission system. However, there are marked differences that may preclude such broad stroke application of this knowledge base without making potentially faulty assumptions. Herein, Zika virus (ZIKV) transmission is reviewed, and the commonalities among these three arboviruses are discussed. Importantly, the divergence of this particular arbovirus is discussed, as is the need to develop ZIKV-specific knowledge base for mitigation of this disease. Specifically reviewed are 1) emergence and persistence patterns, 2) genetic and phenotypic diversity, 3) vector host range, and finally, 4) alternate transmission routes and added complexity of ZIKV transmission and presentation. PMID:26903610

  19. Characterization of Aedes aegypti innate-immune pathways that limit Chikungunya virus replication.

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    Melanie McFarlane

    2014-07-01

    Full Text Available Replication of arboviruses in their arthropod vectors is controlled by innate immune responses. The RNA sequence-specific break down mechanism, RNA interference (RNAi, has been shown to be an important innate antiviral response in mosquitoes. In addition, immune signaling pathways have been reported to mediate arbovirus infections in mosquitoes; namely the JAK/STAT, immune deficiency (IMD and Toll pathways. Very little is known about these pathways in response to chikungunya virus (CHIKV infection, a mosquito-borne alphavirus (Togaviridae transmitted by aedine species to humans resulting in a febrile and arthralgic disease. In this study, the contribution of several innate immune responses to control CHIKV replication was investigated. In vitro experiments identified the RNAi pathway as a key antiviral pathway. CHIKV was shown to repress the activity of the Toll signaling pathway in vitro but neither JAK/STAT, IMD nor Toll pathways were found to mediate antiviral activities. In vivo data further confirmed our in vitro identification of the vital role of RNAi in antiviral defence. Taken together these results indicate a complex interaction between CHIKV replication and mosquito innate immune responses and demonstrate similarities as well as differences in the control of alphaviruses and other arboviruses by mosquito immune pathways.

  20. Antiviral Activity of Diterpene Esters on Chikungunya Virus and HIV Replication.

    Science.gov (United States)

    Nothias-Scaglia, Louis-Félix; Pannecouque, Christophe; Renucci, Franck; Delang, Leen; Neyts, Johan; Roussi, Fanny; Costa, Jean; Leyssen, Pieter; Litaudon, Marc; Paolini, Julien

    2015-06-26

    Recently, new daphnane, tigliane, and jatrophane diterpenoids have been isolated from various Euphorbiaceae species, of which some have been shown to be potent inhibitors of chikungunya virus (CHIKV) replication. To further explore this type of compound, the antiviral activity of a series of 29 commercially available natural diterpenoids was evaluated. Phorbol-12,13-didecanoate (11) proved to be the most potent inhibitor, with an EC50 value of 6.0 ± 0.9 nM and a selectivity index (SI) of 686, which is in line with the previously reported anti-CHIKV potency for the structurally related 12-O-tetradecanoylphorbol-13-acetate (13). Most of the other compounds exhibited low to moderate activity, including an ingenane-type diterpene ester, compound 28, with an EC50 value of 1.2 ± 0.1 μM and SI = 6.4. Diterpene compounds are known also to inhibit HIV replication, so the antiviral activities of compounds 1-29 were evaluated also against HIV-1 and HIV-2. Tigliane- (4β-hydroxyphorbol analogues 10, 11, 13, 15, 16, and 18) and ingenane-type (27 and 28) diterpene esters were shown to inhibit HIV replication in vitro at the nanomolar level. A Pearson analysis performed with the anti-CHIKV and anti-HIV data sets demonstrated a linear relationship, which supported the hypothesis made that PKC may be an important target in CHIKV replication.

  1. Structure-activity relationship study of arbidol derivatives as inhibitors of chikungunya virus replication.

    Science.gov (United States)

    Di Mola, Antonia; Peduto, Antonella; La Gatta, Annalisa; Delang, Leen; Pastorino, Boris; Neyts, Johan; Leyssen, Pieter; de Rosa, Mario; Filosa, Rosanna

    2014-11-01

    Chikungunya virus (CHIKV), a mosquito-borne arthrogenic Alphavirus, causes an acute febrile illness in humans, that is, accompanied by severe joint pains. In many cases, the infection leads to persistent arthralgia, which may last for weeks to several years. The re-emergence of this infection in the early 2000s was exemplified by numerous outbreaks in the eastern hemisphere. Since then, the virus is rapidly spreading. Currently, no drugs have been approved or are in development for the treatment of CHIKV, which makes this viral infection particularly interesting for academic medicinal chemistry efforts. Several molecules have already been identified that inhibit CHIKV replication in phenotypic virus-cell-based assays. One of these is arbidol, a molecule that already has been licensed for the treatment of influenza A and B virus infections. For structural optimization, a dedicated libraries of 43 indole-based derivatives were evaluated leading to more potent analogues (IIIe and IIIf) with anti-chikungunya virus (CHIKV) activities higher than those of the other derivatives, including the lead compound, and with a selective index of inhibition 13.2 and 14.6, respectively, higher than that of ARB (4.6).

  2. CHIKUNGUNYA VIRUS: WHAT DO WE KNOW ABOUT THIS ARBOVIRUS INFECTION? (IN SPANISH

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    Ochoa-Díaz Margarita María

    2014-06-01

    Full Text Available Introduction: for Colombia the arrival of the Chikungunya virus (CHIKV constitutes a potential problem of public health due to in the country as much in rural as urban areas, the presence of the A. Aegypti mosquito, vector of the infection, the same of the dengue virus, is endemic. Objective: To carry out a thematic review referent to the CHIKV and to the febrile syndrome that it causes. Methods: Descriptive bibliographic review, with search in the databases: PubMed, Scopus, ScienceDirect, OvidSP and Medline; including review articles, case reports and clinical trials. Results: 107 articles were found, from which 78 documents were used for convenience between review, research reports, case reports, bulletins and epidemiological reports. Conclusions: The CHIKV is an Alphavirus with an only serotype described. It is one of the 29 species belong to the Alphavirus genus of the Togaviridae family and has two cycles of transmission: Sylvatic or enzootic and urban or epizootic. The incubation period varies between one and twelve days. High fever, cutaneous rash and severe osteoarticular pain are the clinical characteristics that appear in six days, with low lethality and that are difficult to differenciate of other tropical diseases, including Malaria and Dengue. In the majority of the cases, a permanent immunity is acquired. The treatment of the disease is symptomatic and available vaccine does not exist. The sanity authorities must strengthen the programs of vector control to confront this tropical disease. Rev.cienc.biomed. 2014;5(2:317-328. KEYWORDS Chikungunya virus, Chikungunya virus infection, Alphavirus, Alphavirus infections

  3. Emergence of chikungunya virus infection in Orissa, India.

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    Dwibedi, Bhagirathi; Mohapatra, Namita; Beuria, Mihir K; Kerketta, Anna S; Sabat, Jyotsna; Kar, Shantanu K; Rao, Epari V; Hazra, Rupensu K; Parida, Sarat K; Marai, Nitisheel

    2010-05-01

    From September through October 2006, an unknown disease characterized by acute onset of fever, joint pain with or without swelling, and maculopapular rash along with fatigue was reported from three villages of Cuttack and one village of Kendrapara district of Orissa, India, by the State Health Department. Upon learning this, a team from Regional Medical Research Centre (Indian Council of Medical Research), Bhubaneswar, Orissa, conducted an epidemiological investigation in the area. Household survey was carried out and clinical examination of the symptomatic individuals (n = 1289: Kendrapara, 752; Cuttack, 537) undertaken. Based on the recorded chikungunya (CHIK) fever symptoms, a vector-borne viral disease was considered for provisional diagnosis. Blood samples were collected from 217 symptomatic individuals; to confirm the diagnosis, sera were tested for anti-CHIK antibody (immunoglobulin M), which revealed 63% (64/101) and 40% (47/116) seropositivity in the samples from Kendrapara and Cuttack district, respectively. The illness was managed with analgesics like paracetamol. No death was recorded due to the illness. Entomological survey in the areas revealed the presence of Aedes mosquitoes: aegypti, albopictus, and vittatus. The per-man-hour density of Aedes vectors ranged from 0.8 to 7.6. High larval indices, house index >17% and Breteau index >70%, also indicated Aedes breeding in the area. The investigation documented circulation of CHIK in Orissa, India, and helped to take preventive steps in the outbreak area, with the suggested vector control measures. PMID:19874187

  4. Zika virus infections imported from Brazil to Portugal, 2015.

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    Zé-Zé, L; Prata, M B; Teixeira, T; Marques, N; Mondragão, A; Fernandes, R; Saraiva da Cunha, J; Alves, M J

    2016-01-01

    Zika virus is an emerging arbovirus transmitted by Aedes sp. mosquitoes like the Dengue and Chikungunya viruses. Zika virus was until recently considered a mild pathogenic mosquito-borne flavivirus with very few reported benign human infections. In 2007, an epidemic in Micronesia initiated the turnover in the epidemiological history of Zika virus and more recently, the potential association with congenital microcephaly cases in Brazil 2015, still under investigation, led the World Health Organization (WHO) to declare a Public Health Emergency of International Concern on February 1, 2016. Here, we present the clinical and laboratory aspects related to the first four imported human cases of Zika virus in Portugal from Brazil, and alert, regarding the high level of traveling between Portugal and Brazil, and the ongoing expansion of this virus in the Americas, for the threat for Zika virus introduction in Europe and the possible introduction to Madeira Island where Aedes aegypti is present. PMID:27134823

  5. Production of Chikungunya Virus-Like Particles and Subunit Vaccines in Insect Cells.

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    Metz, Stefan W; Pijlman, Gorben P

    2016-01-01

    Chikungunya virus is a reemerging human pathogen that causes debilitating arthritic disease in humans. Like dengue and Zika virus, CHIKV is transmitted by Aedes mosquitoes in an epidemic urban cycle, and is now rapidly spreading through the Americas since its introduction in the Caribbean in late 2013. There are no licensed vaccines or antiviral drugs available, and only a few vaccine candidates have passed Phase I human clinical trials. Using recombinant baculovirus expression technology, we have generated CHIKV glycoprotein subunit and virus-like particle (VLP) vaccines that are amenable to large scale production in insect cells. These vaccines, in particular the VLPs, have shown high immunogenicity and protection against CHIKV infection in different animal models of CHIKV-induced disease. Here, we describe the production, purification, and characterization of these potent CHIKV vaccine candidates. PMID:27233282

  6. Evidence for natural vertical transmission of chikungunya viruses in field populations of Aedes aegypti in Delhi and Haryana states in India-a preliminary report.

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    Jain, Jaspreet; Kushwah, Raja Babu S; Singh, Shashi S; Sharma, Anil; Adak, Tridibes; Singh, Om P; Bhatnagar, Raj Kamal; Subbarao, Sarala K; Sunil, Sujatha

    2016-10-01

    Aedes aegypti and Aedes albopictus are principal vectors for the transmission of chikungunya virus (CHIKV). India is a hub for both dengue and chikungunya infections and there are several reports of co-infection of dengue and chikungunya virus in the clinical scenario. The present pilot entomological survey was conducted to evaluate vertical transmission of CHIKV in Aedes field populations. Aedes immature (larvae and pupae) collection was done in 2012, over a period of six months from selected sites in Delhi and Haryana, India. The immatures collected were reared for adult emergence and species identification was done. A. aegypti male and female mosquitoes were separated and pooled collection spot-wise, RNA extracted and RT PCR performed to test for the presence of CHIKV in the pools. Container index (CI) and minimum infection rate (MIR) were estimated. From study areas that tested positive for CHIKV, adult collections were made and females upon feeding on uninfected blood in laboratory were allowed to lay eggs. The progeny that emerged from these field-collected mothers were tested for CHIKV presence. Our pilot survey showed the existence of A. aegypti population even during peak summer season in a few foci which eventually helped the mosquitoes to tide over adverse environmental conditions and with the start of rainfall, the population exploded within a short period of time. Immatures collected from field and progeny of adults collected from the field were CHIKV positive demonstrating the presence of vertical transmission of chikungunya virus in field population of A. aegypti. The present study further demonstrates the importance of identifying permanent breeding sites for proper Aedes species control. PMID:27282096

  7. A comprehensive immunoinformatics and target site study revealed the corner-stone toward Chikungunya virus treatment.

    Science.gov (United States)

    Hasan, Md Anayet; Khan, Md Arif; Datta, Amit; Mazumder, Md Habibul Hasan; Hossain, Mohammad Uzzal

    2015-05-01

    Recent concerning facts of Chikungunya virus (CHIKV); a Togaviridae family alphavirus has proved this as a worldwide emerging threat which causes Chikungunya fever and devitalizing arthritis. Despite severe outbreaks and lack of antiviral drug, a mere progress has been made regarding to an epitope-based vaccine designed for CHIKV. In this study, we aimed to design an epitope-based vaccine that can trigger a significant immune response as well as to prognosticate inhibitor that can bind with potential drug target sites by using various immunoinformatics and docking simulation tools. Initially, whole proteome of CHIKV was retrieved from database and perused to identify the most immunogenic protein. Structural properties of the selected protein were analyzed. The capacity to induce both humoral and cell-mediated immunity by T cell and B cell were checked for the selected protein. The peptide region spanning 9 amino acids from 397 to 405 and the sequence YYYELYPTM were found as the most potential B cell and T cell epitopes respectively. This peptide could interact with as many as 19 HLAs and showed high population coverage ranging from 69.50% to 84.94%. By using in silico docking techniques the epitope was further assessed for binding against HLA molecules to verify the binding cleft interaction. In addition with this, the allergenicity of the epitopes was also evaluated. In the post therapeutic strategy, three dimensional structure was predicted along with validation and verification that resulted in molecular docking study to identify the potential drug binding sites and suitable therapeutic inhibitor against targeted protein. Finally, pharmacophore study was also performed in quest of seeing potent drug activity. However, this computational epitope-based peptide vaccine designing and target site prediction against CHIKV opens up a new horizon which may be the prospective way in Chikungunya virus research; the results require validation by in vitro and in vivo

  8. Vector Competence of Aedes aegypti and Aedes polynesiensis Populations from French Polynesia for Chikungunya Virus.

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    Vaea Richard

    2016-05-01

    Full Text Available From October 2014 to March 2015, French Polynesia experienced for the first time a chikungunya outbreak. Two Aedes mosquitoes may have contributed to chikungunya virus (CHIKV transmission in French Polynesia: the worldwide distributed Ae. aegypti and the Polynesian islands-endemic Ae. polynesiensis mosquito.To investigate the vector competence of French Polynesian populations of Ae. aegypti and Ae. polynesiensis for CHIKV, mosquitoes were exposed per os at viral titers of 7 logs tissue culture infectious dose 50%. At 2, 6, 9, 14 and 21 days post-infection (dpi, saliva was collected from each mosquito and inoculated onto C6/36 mosquito cells to check for the presence of CHIKV infectious particles. Legs and body (thorax and abdomen of each mosquito were also collected at the different dpi and submitted separately to viral RNA extraction and CHIKV real-time RT-PCR.CHIKV infection rate, dissemination and transmission efficiencies ranged from 7-90%, 18-78% and 5-53% respectively for Ae. aegypti and from 39-41%, 3-17% and 0-14% respectively for Ae. polynesiensis, depending on the dpi. Infectious saliva was found as early as 2 dpi for Ae. aegypti and from 6 dpi for Ae. polynesiensis. Our laboratory results confirm that the French Polynesian population of Ae. aegypti is highly competent for CHIKV and they provide clear evidence for Ae. polynesiensis to act as an efficient CHIKV vector.As supported by our findings, the presence of two CHIKV competent vectors in French Polynesia certainly contributed to enabling this virus to quickly disseminate from the urban/peri-urban areas colonized by Ae. aegypti to the most remote atolls where Ae. polynesiensis is predominating. Ae. polynesiensis was probably involved in the recent chikungunya outbreaks in Samoa and the Cook Islands. Moreover, this vector may contribute to the risk for CHIKV to emerge in other Polynesian islands like Fiji, and more particularly Wallis where there is no Ae. aegypti.

  9. Chikungunya and Dengue Virus Infections Among United States Community Service Volunteers Returning from the Dominican Republic, 2014.

    Science.gov (United States)

    Millman, Alexander J; Esposito, Douglas H; Biggs, Holly M; Decenteceo, Michelle; Klevos, Andrew; Hunsperger, Elizabeth; Munoz-Jordan, Jorge; Kosoy, Olga I; McPherson, Heidi; Sullivan, Carmen; Voorhees, Dayton; Baron, David; Watkins, Jim; Gaul, Linda; Sotir, Mark J; Brunette, Gary; Fischer, Marc; Sharp, Tyler M; Jentes, Emily S

    2016-06-01

    Chikungunya spread throughout the Dominican Republic (DR) after the first identified laboratory-confirmed cases were reported in April 2014. In June 2014, a U.S.-based service organization operating in the DR reported chikungunya-like illnesses among several staff. We assessed the incidence of chikungunya virus (CHIKV) and dengue virus (DENV) infection and illnesses and evaluated adherence to mosquito avoidance measures among volunteers/staff deployed in the DR who returned to the United States during July-August 2014. Investigation participants completed a questionnaire that collected information on demographics, medical history, self-reported illnesses, and mosquito exposures and avoidance behaviors and provided serum for CHIKV and DENV diagnostic testing by reverse transcription polymerase chain reaction and IgM enzyme-linked immunosorbent assay. Of 102 participants, 42 (41%) had evidence of recent CHIKV infection and two (2%) had evidence of recent DENV infection. Of the 41 participants with evidence of recent CHIKV infection only, 39 (95%) reported fever, 37 (90%) reported rash, and 37 (90%) reported joint pain during their assignment. All attended the organization's health trainings, and 89 (87%) sought a pretravel health consultation. Most (∼95%) used insect repellent; however, only 30% applied it multiple times daily and mosquito avoidance measures were inconsistent. Clinicians should discuss chikungunya with travelers visiting areas with ongoing CHIKV outbreaks and should consider chikungunya when diagnosing febrile illnesses in travelers returning from affected areas. PMID:26976891

  10. LC-MS²-Based dereplication of Euphorbia extracts with anti-Chikungunya virus activity.

    Science.gov (United States)

    Nothias-Scaglia, Louis-Félix; Dumontet, Vincent; Neyts, Johan; Roussi, Fanny; Costa, Jean; Leyssen, Pieter; Litaudon, Marc; Paolini, Julien

    2015-09-01

    Recently, phorbol esters from Euphorbiaceae have been shown to elicit potent and selective antiviral activity on the replication of Chikungunya virus (CHIKV) in cell culture. With the objective to found new compounds with anti-CHIKV activities, 45 extracts from various plant parts of 11 Mediterranean Euphorbia and one Mercurialis species were evaluated for selective inhibition of CHIKV replication. All EtOAc extracts, especially those prepared from latex, exhibited significant and selective antiviral activity in a Chikungunya virus-cell-based assay. An LC-MS(2) dereplication method was then developed to investigate whether known diterpenoids with anti-CHIKV activity, such as the potent anti-CHIKV 12-O-tetradecanoylphorbol-13-acetate (TPA), phorbol-12,13-didecanoate, and prostratin as well as 24 other commercially available diterpenoids of tigliane-, ingenane-, and daphnane-type for which the anti-CHIKV activity have been established in advance (Nothias-Scaglia et al. 2015), were present in the Euphorbia extracts. Only ingenol-3-mebutate, 13-O-isobutyryl-12-deoxyphorbol-20-acetate, and ingenol-3,20-dibenzoate, all exhibiting weak anti-CHIKV activities, were detected in the EtOAc extracts of Euphorbia peplus, Euphorbia segetalis ssp. pinea, and Euphorbia pithyusa ssp. pithyusa. Given the potent anti-CHIKV activities of these Euphorbia extracts, the present study suggested that their antiviral activities are probably due to untargeted diterpenoids.

  11. Appearance of E1: A226V mutant Chikungunya virus in Coastal Karnataka, India during 2008 outbreak

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    Khan Mohasin

    2009-10-01

    Full Text Available Abstract Chikungunya has resurged in the form of unprecedented explosive epidemic in 2006 after a long gap in India affecting 1.39 million of persons. The disease continued for the next two consecutive years affecting 59,535 and 64,548 persons during 2007 and 2008 respectively. The 2008 outbreak being the second largest among these three years the information regarding the etiology and the mutations involved are useful for further control measures. Among the 2008 outbreaks the Coastal Karnataka accounts for the 46,510 persons. An in-depth investigation of Chikungunya epidemic of Coastal Karnataka, India, 2008 by serology, virus isolation, RT-PCR and genome sequencing revealed the presence and continued circulation of A226V mutant Chikungunya virus. The appearance of this mutant virus was found to be associated with higher prevalence of vector Aedes albopictus and the geographical proximity of coastal Karnataka with the adjoining Kerala state. This is the first report regarding the appearance of this mutation in Karnataka state of India. The present study identified the presence and association of A226V mutant virus with Chikungunya outbreak in India during 2008.

  12. Appearance of E1: A226V mutant Chikungunya virus in Coastal Karnataka, India during 2008 outbreak.

    Science.gov (United States)

    Santhosh, S R; Dash, Paban Kumar; Parida, Manmohan; Khan, Mohasin; Rao, Putcha V L

    2009-01-01

    Chikungunya has resurged in the form of unprecedented explosive epidemic in 2006 after a long gap in India affecting 1.39 million of persons. The disease continued for the next two consecutive years affecting 59,535 and 64,548 persons during 2007 and 2008 respectively. The 2008 outbreak being the second largest among these three years the information regarding the etiology and the mutations involved are useful for further control measures. Among the 2008 outbreaks the Coastal Karnataka accounts for the 46,510 persons. An in-depth investigation of Chikungunya epidemic of Coastal Karnataka, India, 2008 by serology, virus isolation, RT-PCR and genome sequencing revealed the presence and continued circulation of A226V mutant Chikungunya virus. The appearance of this mutant virus was found to be associated with higher prevalence of vector Aedes albopictus and the geographical proximity of coastal Karnataka with the adjoining Kerala state. This is the first report regarding the appearance of this mutation in Karnataka state of India. The present study identified the presence and association of A226V mutant virus with Chikungunya outbreak in India during 2008. PMID:19857273

  13. Mosquito Rasputin interacts with chikungunya virus nsP3 and determines the infection rate in Aedes albopictus

    NARCIS (Netherlands)

    Fros, Jelke J; Geertsema, Corinne; Zouache, Karima; Baggen, Jim; Domeradzka, Natalia; van Leeuwen, Daniël M; Flipse, Jacky; Vlak, Just M; Failloux, Anna-Bella; Pijlman, Gorben P

    2015-01-01

    BACKGROUND: Chikungunya virus (CHIKV) is an arthritogenic alphavirus (family Togaviridae), transmitted by Aedes species mosquitoes. CHIKV re-emerged in 2004 with multiple outbreaks worldwide and recently reached the Americas where it has infected over a million individuals in a rapidly expanding epi

  14. Chikungunya Virus Nonstructural Protein 2 Inhibits type I/II Interferon-Stimulated JAK-STAT Signaling

    NARCIS (Netherlands)

    Fros, J.; Liu, W.J.; Prow, A.; Geertsema, C.; Ligtenberg, M.; Vanlandingham, D.L.; Schnettler, E.; Vlak, J.M.; Suhrbier, A.; Khromykh, A.A.; Pijlman, G.P.

    2010-01-01

    Chikungunya virus (CHIKV) is an emerging human pathogen transmitted by mosquitoes. Like that of other alphaviruses, CHIKV replication causes general host shutoff, leading to severe cytopathicity in mammalian cells, and inhibits the ability of infected cells to respond to interferon (IFN). Recent res

  15. Chikungunya Virus nsP3 Blocks Stress Granule Assembly by Recruitment of G3BP into Cytoplasmic Foci

    NARCIS (Netherlands)

    Fros, J.J.; Domeradzka, N.E.; Baggen, J.; Geertsema, C.; Flipse, J.; Vlak, J.M.; Pijlman, G.P.

    2012-01-01

    Chikungunya virus nonstructural protein nsP3 has an essential but unknown role in alphavirus replication and interacts with Ras-GAP SH3 domain-binding protein (G3BP). Here we describe the first known function of nsP3, to inhibit stress granule assembly by recruiting G3BP into cytoplasmic foci. A con

  16. Mechanism and role of MCP-1 upregulation upon chikungunya virus infection in human peripheral blood mononuclear cells

    NARCIS (Netherlands)

    Ruiz Silva, Mariana; van der Ende-Metselaar, Heidi; Mulder, H Lie; Smit, Jolanda M; Rodenhuis-Zybert, Izabela A

    2016-01-01

    Monocyte chemoattractant protein-1 (MCP-1/CCL2)-mediated migration of monocytes is essential for immunological surveillance of tissues. During chikungunya virus (CHIKV) infection however, excessive production of MCP-1 has been linked to disease pathogenesis. High MCP-1 serum levels are detected duri

  17. Kinetic analysis of mouse brain proteome alterations following chikungunya virus infection before and after appearance of clinical symptoms

    NARCIS (Netherlands)

    C. Fraisier (Christophe); P. Koraka (Penelope); M. Belghazi (Maya); M. Bakli (Mahfoud); S. Granjeaud (Samuel); M. Pophillat (Matthieu); S.M. Lim (Stephanie); A.D.M.E. Osterhaus (Albert); B.E.E. Martina (Byron); L. Camoin (Luc); L. Almeras (Lionel)

    2014-01-01

    textabstractRecent outbreaks of Chikungunya virus (CHIKV) infection have been characterized by an increasing number of severe cases with atypical manifestations including neurological complications. In parallel, the risk map of CHIKV outbreaks has expanded because of improved vector competence. Thes

  18. Mosquito Rasputin interacts with chikungunya virus nsP3 and determines the infection rate in Aedes albopictus

    NARCIS (Netherlands)

    Fros, J.J.; Geertsema, Corinne; Zouache, Karima; Baggen, Jim; Domeradzka, Natalia; Leeuwen, Van D.M.; Flipse, Jacky; Vlak, J.M.; Failloux, Anna Bella; Pijlman, G.P.

    2015-01-01

    Background: Chikungunya virus (CHIKV) is an arthritogenic alphavirus (family Togaviridae), transmitted by Aedes species mosquitoes. CHIKV re-emerged in 2004 with multiple outbreaks worldwide and recently reached the Americas where it has infected over a million individuals in a rapidly expanding

  19. Multidisciplinary prospective study of mother-to-child chikungunya virus infections on the island of La Reunion.

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    Patrick Gérardin

    2008-03-01

    Full Text Available BACKGROUND: An outbreak of chikungunya virus affected over one-third of the population of La Réunion Island between March 2005 and December 2006. In June 2005, we identified the first case of mother-to-child chikungunya virus transmission at the Groupe Hospitalier Sud-Réunion level-3 maternity department. The goal of this prospective study was to characterize the epidemiological, clinical, biological, and radiological features and outcomes of all the cases of vertically transmitted chikungunya infections recorded at our institution during this outbreak. METHODS AND FINDINGS: Over 22 mo, 7,504 women delivered 7,629 viable neonates; 678 (9.0% of these parturient women were infected (positive RT-PCR or IgM serology during antepartum, and 61 (0.8% in pre- or intrapartum. With the exception of three early fetal deaths, vertical transmission was exclusively observed in near-term deliveries (median duration of gestation: 38 wk, range 35-40 wk in the context of intrapartum viremia (19 cases of vertical transmission out of 39 women with intrapartum viremia, prevalence rate 0.25%, vertical transmission rate 48.7%. Cesarean section had no protective effect on transmission. All infected neonates were asymptomatic at birth, and median onset of neonatal disease was 4 d (range 3-7 d. Pain, prostration, and fever were present in 100% of cases and thrombocytopenia in 89%. Severe illness was observed in ten cases (52.6% and mainly consisted of encephalopathy (n = 9; 90%. These nine children had pathologic MRI findings (brain swelling, n = 9; cerebral hemorrhages, n = 2, and four evolved towards persistent disabilities. CONCLUSIONS: Mother-to-child chikungunya virus transmission is frequent in the context of intrapartum maternal viremia, and often leads to severe neonatal infection. Chikungunya represents a substantial risk for neonates born to viremic parturients that should be taken into account by clinicians and public health authorities in the event of a

  20. Detection of Chikungunya virus in wild populations of Aedes albopictus in Kerala State, India.

    Science.gov (United States)

    Kumar, Narendran Pradeep; Sabesan, Shanmugavelu; Krishnamoorthy, Kaliannagounder; Jambulingam, Purushothaman

    2012-10-01

    We detected Chikungunya virus (CHIKV) infection among wild populations of Aedes albopictus female specimens during the CHIKV outbreaks of 2009 and 2006 collected in different localities in Kerala State, India. The envelope 1 gene (E1) sequences of the virus isolate 2009 from the mosquito species showed close genetic relatedness (Kimura 2 Parameter genetic distance=0.0013) to CHIKV-positive isolates from human serum samples from the same area. E1 gene sequences from Ae. albopictus, as well as from human isolates, had the crucial non-synonymous C/T mutation at position 10670, leading to the A226V amino acid change. This natural inclination indicated the role of this mosquito species in the transmission of CHIKV during its recent outbreaks in Kerala State. PMID:22925018

  1. Phylogenetic analyses of chikungunya virus among travelers in Rio de Janeiro, Brazil, 2014-2015

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    Liliane Costa Conteville

    2016-01-01

    Full Text Available Chikungunya virus (CHIKV is a mosquito-borne pathogen that emerged in Brazil by late 2014. In the country, two CHIKV foci characterized by the East/Central/South Africa and Asian genotypes, were established in North and Northeast regions. We characterized, by phylogenetic analyses of full and partial genomes, CHIKV from Rio de Janeiro state (2014-2015. These CHIKV strains belong to the Asian genotype, which is the determinant of the current Northern Brazilian focus, even though the genome sequence presents particular single nucleotide variations. This study provides the first genetic characterisation of CHIKV in Rio de Janeiro and highlights the potential impact of human mobility in the spread of an arthropod-borne virus.

  2. Effective chikungunya virus-like particle vaccine produced in insect cells.

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    Stefan W Metz

    Full Text Available The emerging arthritogenic, mosquito-borne chikungunya virus (CHIKV causes severe disease in humans and represents a serious public health threat in countries where Aedes spp mosquitoes are present. This study describes for the first time the successful production of CHIKV virus-like particles (VLPs in insect cells using recombinant baculoviruses. This well-established expression system is rapidly scalable to volumes required for epidemic responses and proved well suited for processing of CHIKV glycoproteins and production of enveloped VLPs. Herein we show that a single immunization with 1 µg of non-adjuvanted CHIKV VLPs induced high titer neutralizing antibody responses and provided complete protection against viraemia and joint inflammation upon challenge with the Réunion Island CHIKV strain in an adult wild-type mouse model of CHIKV disease. CHIKV VLPs produced in insect cells using recombinant baculoviruses thus represents as a new, safe, non-replicating and effective vaccine candidate against CHIKV infections.

  3. Deliberate attenuation of chikungunya virus by adaptation to heparan sulfate-dependent infectivity: a model for rational arboviral vaccine design.

    Science.gov (United States)

    Gardner, Christina L; Hritz, Jozef; Sun, Chengqun; Vanlandingham, Dana L; Song, Timothy Y; Ghedin, Elodie; Higgs, Stephen; Klimstra, William B; Ryman, Kate D

    2014-02-01

    Mosquito-borne chikungunya virus (CHIKV) is a positive-sense, single-stranded RNA virus from the genus Alphavirus, family Togaviridae, which causes fever, rash and severe persistent polyarthralgia in humans. Since there are currently no FDA licensed vaccines or antiviral therapies for CHIKV, the development of vaccine candidates is of critical importance. Historically, live-attenuated vaccines (LAVs) for protection against arthropod-borne viruses have been created by blind cell culture passage leading to attenuation of disease, while maintaining immunogenicity. Attenuation may occur via multiple mechanisms. However, all examined arbovirus LAVs have in common the acquisition of positively charged amino acid substitutions in cell-surface attachment proteins that render virus infection partially dependent upon heparan sulfate (HS), a ubiquitously expressed sulfated polysaccharide, and appear to attenuate by retarding dissemination of virus particles in vivo. We previously reported that, like other wild-type Old World alphaviruses, CHIKV strain, La Réunion, (CHIKV-LR), does not depend upon HS for infectivity. To deliberately identify CHIKV attachment protein mutations that could be combined with other attenuating processes in a LAV candidate, we passaged CHIKV-LR on evolutionarily divergent cell-types. A panel of single amino acid substitutions was identified in the E2 glycoprotein of passaged virus populations that were predicted to increase electrostatic potential. Each of these substitutions was made in the CHIKV-LR cDNA clone and comparisons of the mutant viruses revealed surface exposure of the mutated residue on the spike and sensitivity to competition with the HS analog, heparin, to be primary correlates of attenuation in vivo. Furthermore, we have identified a mutation at E2 position 79 as a promising candidate for inclusion in a CHIKV LAV.

  4. Molecular characterization of Chikungunya virus during an outbreak in South India

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    Srikanth P

    2010-01-01

    Full Text Available Introduction: Re-emergence of Chikungunya is a major public health problem in the southern states of India. Objectives: This study was undertaken to investigate an outbreak of Chikungunya, in June-August 2008 using PCR and determine the prevalent genotypes of Chikungunya virus (CHIKV associated with the outbreak. Materials and Methods: Samples of blood were collected (in heparinized vacutainer tubes from suspected patients of CHIKV infection from both Government Taluk Hospital in Kerala and a tertiary care hospital in Chennai, Tamil Nadu. A one-step RT-PCR was carried out on a block thermo-cycler targeting the E2 gene that codes for the viral envelope protein. The amplicons were verified for 305 bp size by standard agarose gel electrophoresis. The PCR products were purified, sequenced, and compared with other CHIKV strains reported from different geographical regions. A phylogenetic tree was constructed using MEGA 4. Results: Altogether 118 samples were collected from patients who presented with sudden onset of fever and/or joint pain, myalgia, and headache. CHIKV infection was confirmed by RT-PCR in 14 patients and all these cases were from Kerala. The positivity correlated with the early stage of the disease as all these patients had fever of less than seven days duration. The study isolates have been allotted the GenBank accession nos. GQ272368-GQ272381. Phylogenetic analysis of recent CHIKV isolates by partial sequencing of E2 region shows that isolates are closely related to strains from neighboring states and the African type. Conclusion: RT-PCR is a useful technique for the early detection of CHIKV infection during outbreaks. Molecular characterization of the strains indicates that majority of the strains have originated from the Central/East African strains of CHIKV.

  5. Chikungunya: a reemerging infection spreading during 2010 dengue fever outbreak in National Capital Region of India.

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    Ramachandran, V G; Das, Shukla; Roy, Priyamvada; Hada, Vivek; Mogha, Narendra Singh

    2016-06-01

    Chikungunya fever is an important reemerging arbovirus illness, which is transmitted by the same vector as of dengue virus. Many cases of concurrent infections with multiple dengue virus serotypes have been reported in many countries. Also, concurrent infection with Chikungunya virus and dengue virus has been reported in the past in Delhi. Therefore, this study was done to detect Chikungunya IgM antibodies in suspected dengue fever patients. In this study, 1666 serum samples suspected of dengue fever and collected during the outbreak period (August 2010-December 2010) were tested for dengue IgM antibodies, of which 736 tested negative. Of the 736 dengue IgM negative sera, 666 were tested for Chikungunya IgM antibodies. The demographic profile and essential laboratory investigations were recorded. Chikungunya IgM was detected in 9.91 % of the patients. During the post-monsoon period though dengue dominated in numbers, the number of Chikungunya fever cases increased gradually followed by an abrupt decrease with the onset of winter. The Chikungunya IgM positive patients were suffering from fever of more than 5 days duration and had thrombocytopenia. Due to similarity in clinical features and vector transmitting dengue and Chikungunya virus, continuous surveillance of both dengue fever and Chikungunya fever is desirable for better management and epidemiological assessment. PMID:27366770

  6. Structural analyses at pseudo atomic resolution of Chikungunya virus and antibodies show mechanisms of neutralization.

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    Sun, Siyang; Xiang, Ye; Akahata, Wataru; Holdaway, Heather; Pal, Pankaj; Zhang, Xinzheng; Diamond, Michael S; Nabel, Gary J; Rossmann, Michael G

    2013-04-02

    A 5.3 Å resolution, cryo-electron microscopy (cryoEM) map of Chikungunya virus-like particles (VLPs) has been interpreted using the previously published crystal structure of the Chikungunya E1-E2 glycoprotein heterodimer. The heterodimer structure was divided into domains to obtain a good fit to the cryoEM density. Differences in the T = 4 quasi-equivalent heterodimer components show their adaptation to different environments. The spikes on the icosahedral 3-fold axes and those in general positions are significantly different, possibly representing different phases during initial generation of fusogenic E1 trimers. CryoEM maps of neutralizing Fab fragments complexed with VLPs have been interpreted using the crystal structures of the Fab fragments and the VLP structure. Based on these analyses the CHK-152 antibody was shown to stabilize the viral surface, hindering the exposure of the fusion-loop, likely neutralizing infection by blocking fusion. The CHK-9, m10 and m242 antibodies surround the receptor-attachment site, probably inhibiting infection by blocking cell attachment. DOI:http://dx.doi.org/10.7554/eLife.00435.001.

  7. Transmission potential of chikungunya virus and control measures: the case of Italy.

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    Piero Poletti

    Full Text Available During summer 2007 Italy has experienced an epidemic caused by Chikungunya virus - the first large outbreak documented in a temperate climate country - with approximately 161 laboratory confirmed cases concentrated in two bordering villages in North-Eastern Italy comprising 3,968 inhabitants. The seroprevalence was recently estimated to be 10.2%. In this work we provide estimates of the transmission potential of the virus and we assess the efficacy of the measures undertaken by public health authorities to control the epidemic spread. To such aim, we developed a model describing the temporal dynamics of the competent vector, known as Aedes albopictus, explicitly depending on climatic factors, coupled to an epidemic transmission model describing the spread of the epidemic in both humans and mosquitoes. The cumulative number of notified cases predicted by the model was 185 on average (95% CI 117-278, in good agreement with observed data. The probability of observing a major outbreak after the introduction of an infective human case was estimated to be in the range of 32%-76%. We found that the basic reproduction number was in the range of 1.8-6 but it could have been even larger, depending on the density of mosquitoes, which in turn depends on seasonal meteorological effects, besides other local abiotic factors. These results confirm the increasing risk of tropical vector-borne diseases in temperate climate countries, as a consequence of globalization. However, our results show that an epidemic can be controlled by performing a timely intervention, even if the transmission potential of Chikungunya virus is sensibly high.

  8. Easy and inexpensive molecular detection of dengue, chikungunya and zika viruses in febrile patients.

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    Calvo, Eliana P; Sánchez-Quete, Fernando; Durán, Sandra; Sandoval, Isabel; Castellanos, Jaime E

    2016-11-01

    Dengue (DENV), chikungunya (CHIKV) and zika (ZIKV) are arthropod-borne viruses (arboviruses) sharing a common vector, the mosquito Aedes aegypti. At initial stages, patients infected with these viruses have similar clinical manifestations, however, the outcomes and clinical management of these diseases are different, for this reason early and accurate identification of the causative virus is necessary. This paper reports the development of a rapid and specific nested-PCR for detection of DENV, CHIKV and ZIKV infection in the same sample. A set of six outer primers targeting the C-preM, E1, and E gene respectively was used in a multiplex one-step RT-PCR assay, followed by the second round of amplification with specific inner primers for each virus. The specificity of the present assay was validated with positive and negative serum samples for viruses and supernatants of infected cells. The assay was tested using clinical samples from febrile patients. In these samples, we detected mono and dual infections and a case of triple co-infection DENV-CHIKV-ZIKV. This assay might be a useful and an inexpensive tool for detection of these infections in regions where these arboviruses co-circulate. PMID:27477452

  9. Easy and inexpensive molecular detection of dengue, chikungunya and zika viruses in febrile patients.

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    Calvo, Eliana P; Sánchez-Quete, Fernando; Durán, Sandra; Sandoval, Isabel; Castellanos, Jaime E

    2016-11-01

    Dengue (DENV), chikungunya (CHIKV) and zika (ZIKV) are arthropod-borne viruses (arboviruses) sharing a common vector, the mosquito Aedes aegypti. At initial stages, patients infected with these viruses have similar clinical manifestations, however, the outcomes and clinical management of these diseases are different, for this reason early and accurate identification of the causative virus is necessary. This paper reports the development of a rapid and specific nested-PCR for detection of DENV, CHIKV and ZIKV infection in the same sample. A set of six outer primers targeting the C-preM, E1, and E gene respectively was used in a multiplex one-step RT-PCR assay, followed by the second round of amplification with specific inner primers for each virus. The specificity of the present assay was validated with positive and negative serum samples for viruses and supernatants of infected cells. The assay was tested using clinical samples from febrile patients. In these samples, we detected mono and dual infections and a case of triple co-infection DENV-CHIKV-ZIKV. This assay might be a useful and an inexpensive tool for detection of these infections in regions where these arboviruses co-circulate.

  10. Development of field-based real-time reverse transcription-polymerase chain reaction assays for detection of Chikungunya and O'nyong-nyong viruses in mosquitoes.

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    Smith, Darci R; Lee, John S; Jahrling, Jordan; Kulesh, David A; Turell, Michael J; Groebner, Jennifer L; O'Guinn, Monica L

    2009-10-01

    Chikungunya (CHIK) and O'nyong-nyong (ONN) are important emerging arthropod-borne diseases. Molecular diagnosis of these two viruses in mosquitoes has not been evaluated, and the effects of extraneous mosquito tissue on assay performance have not been tested. Additionally, no real-time reverse transcription-polymerase chain reaction (RT-PCR) assay exists for detecting ONN virus (ONNV) RNA. We describe the development of sensitive and specific real-time RT-PCR assays for detecting CHIK and ONN viral RNA in mosquitoes, which have application for field use. In addition, we compared three methods for primer/probe design for assay development by evaluating their sensitivity and specificity. This comparison resulted in development of virus-specific assays that could detect less than one plaque-forming unit equivalent of each of the viruses in mosquitoes. The use of these assays will aid in arthropod-borne disease surveillance and in the control of the associated diseases.

  11. Chikungunya, climate change, and human rights.

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    Meason, Braden; Paterson, Ryan

    2014-06-14

    Chikungunya is a re-emerging arbovirus that causes significant morbidity and some mortality. Global climate change leading to warmer temperatures and changes in rainfall patterns allow mosquito vectors to thrive at altitudes and at locations where they previously have not, ultimately leading to a spread of mosquito-borne diseases. While mutations to the chikungunya virus are responsible for some portion of the re-emergence, chikungunya epidemiology is closely tied with weather patterns in Southeast Asia. Extrapolation of this regional pattern, combined with known climate factors impacting the spread of malaria and dengue, summate to a dark picture of climate change and the spread of this disease from south Asia and Africa into Europe and North America. This review describes chikungunya and collates current data regarding its spread in which climate change plays an important part. We also examine human rights obligations of States and others to protect against this disease.

  12. Chikungunya virus in Colombia: Clinical and epidemiological aspects, and literature review

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    Zuluaga Gómez, Mateo

    2016-01-01

    Full Text Available In recent years, with the movement of populations and with globalization, some infections and diseases have changed from endemic to epidemic in certain regions. Such is the case of chikungunya virus (CHIKV, a re-emerging arbovirus that has triggered global alarm. According to the Center for Disease Control and Prevention (CDC, until January 2015, there had been case reports from 42 countries in the Caribbean, and Central, South, and North America, with more than one million suspected cases and about thirty thousand laboratory-confirmed cases. The latest report in Colombia by Instituto Nacional de Salud refers to a total of 231.392 clinically confirmed cases (suggestive symptoms associated with CHIKV, 1.528 cases confirmed by laboratory, and 3.848 suspected cases, for an overall total of 236.768. In this review, the following aspects of CHIKV infection are included: virology, transmission by vector, pathogenesis, epidemiology, clinical manifestations, laboratory tests, preventive measures and future prospects.

  13. Seroprevalence and entomological study on Chikungunya virus at the Croatian littoral.

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    Vilibic-Cavlek, Tatjana; Pem-Novosel, Iva; Kaic, Bernard; Babić-Erceg, Andrea; Kucinar, Jasmina; Klobucar, Ana; Medic, Alan; Pahor, Djana; Barac-Juretic, Katija; Gjenero-Margan, Ira

    2015-06-01

    During 2011-2012, a total of 1008 serum samples from randomly selected inhabitants of seven Croatian counties located on the Adriatic Coast were tested for the presence of chikungunya virus (CHIKV) IgG antibodies using indirect immunofluorescence assay. Nine participants (0.9%) from four counties were found to be seropositive to CHIKV. Seroprevalence varied from 0.5% to 1.8% between counties. Additionally, a total of 3,699 mosquitoes were captured in 126 localities from August 16 to September 24, 2011. Three mosquito species were found: Ae. albopictus (3010/81.4%), Cx. pipiens (688/18.6%) and only one specimen of the Cs. longiareolata. Female mosquitoes (N = 1,748) were pooled. All pools tested negative for CHIKV RNA using a real-time RT-PCR.

  14. Western Blot Detection of Human Anti-Chikungunya Virus Antibody with Recombinant Envelope 2 Protein.

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    Yang, Zhaoshou; Lee, Jihoo; Ahn, Hye-Jin; Chong, Chom-Kyu; Dias, Ronaldo F; Nam, Ho-Woo

    2016-04-01

    Chikungunya virus (CHIKV), a tropical pathogen, has re-emerged and has massive outbreaks abruptly all over the world. Containing many dominant epitopes, the envelope E2 protein of CHIKV has been explored for the vaccination or diagnosis. In the present study, the antigenicity of a recombinant expressed intrinsically disorder domain (IUD) of E2 was tested for the detection of the antibody against CHIKV through western blot method. The gene of the IUD of E2 was inserted into 2 different vectors and expressed as recombinant GST-E2 and recombinant MBP-E2 fusion protein, respectively. Two kinds of fusion proteins were tested with 30 CHIKV patient sera and 30 normal sera, respectively. Both proteins were detected by 25 patients sera (83.3%) and 1 normal serum (3.3%). This test showed a relatively high sensitivity and very high specificity of the recombinant E2 proteins to be used as diagnostic antigens against CHIKV infection. PMID:27180586

  15. Nonhuman Primate Models of Chikungunya Virus Infection and Disease (CHIKV NHP Model).

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    Broeckel, Rebecca; Haese, Nicole; Messaoudi, Ilhem; Streblow, Daniel N

    2015-01-01

    Chikungunya virus (CHIKV) is a positive-sense RNA virus transmitted by Aedes mosquitoes. CHIKV is a reemerging Alphavirus that causes acute febrile illness and severe and debilitating polyarthralgia of the peripheral joints. Huge epidemics and the rapid spread of CHIKV seen in India and the Indian Ocean region established CHIKV as a global health concern. This concern was further solidified by the recent incursion of the virus into the Western hemisphere, a region without pre-existing immunity. Nonhuman primates (NHPs) serve as excellent animal models for understanding CHIKV pathogenesis and pre-clinical assessment of vaccines and therapeutics. NHPs present advantages over rodent models because they are a natural amplification host for CHIKV and they share significant genetic and physiological homology with humans. CHIKV infection in NHPs results in acute fever, rash, viremia and production of type I interferon. NHPs develop CHIKV-specific B and T-cells, generating neutralizing antibodies and CHIKV-specific CD4⁺ and CD8⁺ T-cells. CHIKV establishes a persistent infection in NHPs, particularly in cynomolgus macaques, because infectious virus could be recovered from spleen, liver, and muscle as late as 44 days post infection. NHPs are valuable models that are useful in preclinical testing of vaccines and therapeutics and uncovering the details of CHIKV pathogenesis. PMID:26389957

  16. Nonhuman Primate Models of Chikungunya Virus Infection and Disease (CHIKV NHP Model

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    Rebecca Broeckel

    2015-09-01

    Full Text Available Chikungunya virus (CHIKV is a positive-sense RNA virus transmitted by Aedes mosquitoes. CHIKV is a reemerging Alphavirus that causes acute febrile illness and severe and debilitating polyarthralgia of the peripheral joints. Huge epidemics and the rapid spread of CHIKV seen in India and the Indian Ocean region established CHIKV as a global health concern. This concern was further solidified by the recent incursion of the virus into the Western hemisphere, a region without pre-existing immunity. Nonhuman primates (NHPs serve as excellent animal models for understanding CHIKV pathogenesis and pre-clinical assessment of vaccines and therapeutics. NHPs present advantages over rodent models because they are a natural amplification host for CHIKV and they share significant genetic and physiological homology with humans. CHIKV infection in NHPs results in acute fever, rash, viremia and production of type I interferon. NHPs develop CHIKV-specific B and T-cells, generating neutralizing antibodies and CHIKV-specific CD4+ and CD8+ T-cells. CHIKV establishes a persistent infection in NHPs, particularly in cynomolgus macaques, because infectious virus could be recovered from spleen, liver, and muscle as late as 44 days post infection. NHPs are valuable models that are useful in preclinical testing of vaccines and therapeutics and uncovering the details of CHIKV pathogenesis.

  17. Antagonism of the Sodium-Potassium ATPase Impairs Chikungunya Virus Infection

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    Alison W. Ashbrook

    2016-05-01

    Full Text Available Chikungunya virus (CHIKV is a reemerging alphavirus that has caused epidemics of fever, arthralgia, and rash worldwide. There are currently no licensed vaccines or antiviral therapies available for the prevention or treatment of CHIKV disease. We conducted a high-throughput, chemical compound screen that identified digoxin, a cardiac glycoside that blocks the sodium-potassium ATPase, as a potent inhibitor of CHIKV infection. Treatment of human cells with digoxin or a related cardiac glycoside, ouabain, resulted in a dose-dependent decrease in infection by CHIKV. Inhibition by digoxin was cell type-specific, as digoxin treatment of either murine or mosquito cells did not diminish CHIKV infection. Digoxin displayed antiviral activity against other alphaviruses, including Ross River virus and Sindbis virus, as well as mammalian reovirus and vesicular stomatitis virus. The digoxin-mediated block to CHIKV and reovirus infection occurred at one or more postentry steps, as digoxin inhibition was not bypassed by fusion of CHIKV at the plasma membrane or infection with cell surface-penetrating reovirus entry intermediates. Selection of digoxin-resistant CHIKV variants identified multiple mutations in the nonstructural proteins required for replication complex formation and synthesis of viral RNA. These data suggest a role for the sodium-potassium ATPase in promoting postentry steps of CHIKV replication and provide rationale for modulation of this pathway as a broad-spectrum antiviral strategy.

  18. A Wolbachia wMel transinfection in Aedes albopictus is not detrimental to host fitness and inhibits Chikungunya virus.

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    Marcus S C Blagrove

    Full Text Available BACKGROUND: Wolbachia inherited intracellular bacteria can manipulate the reproduction of their insect hosts through cytoplasmic incompatibility (CI, and certain strains have also been shown to inhibit the replication or dissemination of viruses. Wolbachia strains also vary in their relative fitness effects on their hosts and this is a particularly important consideration with respect to the potential of newly created transinfections for use in disease control. METHODOLOGY/PRINCIPAL FINDINGS: In Aedes albopictus mosquitoes transinfected with the wMel strain from Drosophila melanogaster, which we previously reported to be unable to transmit dengue in lab challenges, no significant detrimental effects were observed on egg hatch rate, fecundity, adult longevity or male mating competitiveness. All these parameters influence the population dynamics of Wolbachia, and the data presented are favourable with respect to the aim of taking wMel to high population frequency. Challenge with the chikungunya (CHIKV virus, for which Ae. albopictus is an important vector, was conducted and the presence of wMel abolished CHIKV dissemination to the saliva. CONCLUSIONS/SIGNIFICANCE: Taken together, these data suggest that introducing wMel into natural Ae. albopictus populations using bidirectional CI could be an efficient strategy for preventing or reducing the transmission of arboviruses by this species.

  19. Genetic diversity of Chikungunya virus, India 2006-2010: evolutionary dynamics and serotype analyses.

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    Sumathy, K; Ella, Krishna M

    2012-03-01

    The genetic diversity of Chikungunya virus (CHIKV) causing recurring outbreaks in India since 2006 was studied. The 2006 epidemic was caused by a virus strain of the East, Central and South African (ECSA) genotype with 226A in the E1 glycoprotein. The variant strain with E1-A226V mutation caused outbreaks since 2007 in the state of Kerala where Aedes albopictus is the abundant mosquito vector. Molecular epidemiology data since 2007 is scarce from other regions of the country. RT-PCR, sequencing and phylogenetic analyses of CHIKV isolates from the 2009 to 2010 epidemics in the States of Tamil Nadu and Andhra Pradesh placed them in a separate clade within the ECSA lineage. The isolates of the study had 226A in the E1 glycoprotein. The isolates had a novel E1-K211E mutation that was under significant positive selection. E1-211E is highly conserved in the Asian genotype of the virus circulated by Aedes aegypti. Unique mutations in E2 glycoprotein were identified. The two sub-lineages of ECSA genotype circulating in India parallel the abundance of Ae. albopictus and Ae. aegypti. Novel mutations in the envelope glycoproteins suggest adaptive evolution of the virus to local vector abundance. Cross neutralization of the virus isolates from recurring Indian epidemics indicated that no distinct serotypes had evolved. The study has provided insights into the origin, distribution and evolutionary adaptation of the virus to local vector abundance in the region that has reportedly, the highest incidence of CHIKV infection in the world. PMID:22246833

  20. The wMel Strain of Wolbachia Reduces Transmission of Chikungunya Virus in Aedes aegypti.

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    Matthew T Aliota

    2016-04-01

    Full Text Available New approaches to preventing chikungunya virus (CHIKV are needed because current methods are limited to controlling mosquito populations, and they have not prevented the invasion of this virus into new locales, nor have they been sufficient to control the virus upon arrival. A promising candidate for arbovirus control and prevention relies on the introduction of the intracellular bacterium Wolbachia into Aedes aegypti mosquitoes. This primarily has been proposed as a tool to control dengue virus (DENV transmission; however, evidence suggests Wolbachia infections confer protection for Ae. aegypti against CHIKV. Although this approach holds much promise for limiting virus transmission, at present our understanding of the ability of CHIKV to infect, disseminate, and be transmitted by wMel-infected Ae. aegypti currently being used at Wolbachia release sites is limited.Using Ae. aegypti infected with the wMel strain of Wolbachia that are being released in Medellin, Colombia, we report that these mosquitoes have reduced vector competence for CHIKV, even with extremely high viral titers in the bloodmeal. In addition, we examined the dynamics of CHIKV infection over the course of four to seven days post feeding. Wolbachia-infected mosquitoes remained non-infective over the duration of seven days, i.e., no infectious virus was detected in the saliva when exposed to bloodmeals of moderate viremia, but CHIKV-exposed, wild type mosquitoes did have viral loads in the saliva consistent with what has been reported elsewhere. Finally, the presence of wMel infection had no impact on the lifespan of mosquitoes as compared to wild type mosquitoes following CHIKV infection.These results could have an impact on vector control strategies in areas where Ae. aegypti are transmitting both DENV and CHIKV; i.e., they argue for further exploration, both in the laboratory and the field, on the feasibility of expanding this technology beyond DENV.

  1. Genetic diversity of Chikungunya virus, India 2006-2010: evolutionary dynamics and serotype analyses.

    Science.gov (United States)

    Sumathy, K; Ella, Krishna M

    2012-03-01

    The genetic diversity of Chikungunya virus (CHIKV) causing recurring outbreaks in India since 2006 was studied. The 2006 epidemic was caused by a virus strain of the East, Central and South African (ECSA) genotype with 226A in the E1 glycoprotein. The variant strain with E1-A226V mutation caused outbreaks since 2007 in the state of Kerala where Aedes albopictus is the abundant mosquito vector. Molecular epidemiology data since 2007 is scarce from other regions of the country. RT-PCR, sequencing and phylogenetic analyses of CHIKV isolates from the 2009 to 2010 epidemics in the States of Tamil Nadu and Andhra Pradesh placed them in a separate clade within the ECSA lineage. The isolates of the study had 226A in the E1 glycoprotein. The isolates had a novel E1-K211E mutation that was under significant positive selection. E1-211E is highly conserved in the Asian genotype of the virus circulated by Aedes aegypti. Unique mutations in E2 glycoprotein were identified. The two sub-lineages of ECSA genotype circulating in India parallel the abundance of Ae. albopictus and Ae. aegypti. Novel mutations in the envelope glycoproteins suggest adaptive evolution of the virus to local vector abundance. Cross neutralization of the virus isolates from recurring Indian epidemics indicated that no distinct serotypes had evolved. The study has provided insights into the origin, distribution and evolutionary adaptation of the virus to local vector abundance in the region that has reportedly, the highest incidence of CHIKV infection in the world.

  2. The wMel Strain of Wolbachia Reduces Transmission of Chikungunya Virus in Aedes aegypti

    Science.gov (United States)

    Aliota, Matthew T.; Walker, Emma C.; Uribe Yepes, Alexander; Dario Velez, Ivan; Christensen, Bruce M.; Osorio, Jorge E.

    2016-01-01

    Background New approaches to preventing chikungunya virus (CHIKV) are needed because current methods are limited to controlling mosquito populations, and they have not prevented the invasion of this virus into new locales, nor have they been sufficient to control the virus upon arrival. A promising candidate for arbovirus control and prevention relies on the introduction of the intracellular bacterium Wolbachia into Aedes aegypti mosquitoes. This primarily has been proposed as a tool to control dengue virus (DENV) transmission; however, evidence suggests Wolbachia infections confer protection for Ae. aegypti against CHIKV. Although this approach holds much promise for limiting virus transmission, at present our understanding of the ability of CHIKV to infect, disseminate, and be transmitted by wMel-infected Ae. aegypti currently being used at Wolbachia release sites is limited. Methodology/Principal Findings Using Ae. aegypti infected with the wMel strain of Wolbachia that are being released in Medellin, Colombia, we report that these mosquitoes have reduced vector competence for CHIKV, even with extremely high viral titers in the bloodmeal. In addition, we examined the dynamics of CHIKV infection over the course of four to seven days post feeding. Wolbachia-infected mosquitoes remained non-infective over the duration of seven days, i.e., no infectious virus was detected in the saliva when exposed to bloodmeals of moderate viremia, but CHIKV-exposed, wild type mosquitoes did have viral loads in the saliva consistent with what has been reported elsewhere. Finally, the presence of wMel infection had no impact on the lifespan of mosquitoes as compared to wild type mosquitoes following CHIKV infection. Conclusions/Significance These results could have an impact on vector control strategies in areas where Ae. aegypti are transmitting both DENV and CHIKV; i.e., they argue for further exploration, both in the laboratory and the field, on the feasibility of expanding this

  3. In silico study on anti-Chikungunya virus activity of hesperetin

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    Oo, Adrian; Hassandarvish, Pouya; Chin, Sek Peng; Abu Bakar, Sazaly

    2016-01-01

    Background The re-emerging, Aedes spp. transmitted Chikungunya virus (CHIKV) has recently caused large outbreaks in a wide geographical distribution of the world including countries in Europe and America. Though fatalities associated with this self-remitting disease were rarely reported, quality of patients’ lives have been severely diminished by polyarthralgia recurrence. Neither effective antiviral treatment nor vaccines are available for CHIKV. Our previous in vitro screening showed that hesperetin, a bioflavonoid exhibits inhibitory effect on the virus intracellular replication. Here, we present a study using the computational approach to identify possible target proteins for future mechanistic studies of hesperetin. Methods 3D structures of CHIKV nsP2 (3TRK) and nsP3 (3GPG) were retrieved from Protein Data Bank (PDB), whereas nsP1, nsP4 and cellular factor SPK2 were modeled using Iterative Threading Assembly Refinement (I-TASSER) server based on respective amino acids sequence. We performed molecular docking on hesperetin against all four CHIKV non-structural proteins and SPK2. Proteins preparation and subsequent molecular docking were performed using Discovery Studio 2.5 and AutoDock Vina 1.5.6. The Lipinski’s values of the ligand were computed and compared with the available data from PubChem. Two non-structural proteins with crystal structures 3GPG and 3TRK in complexed with hesperetin, demonstrated favorable free energy of binding from the docking study, were further explored using molecular dynamics (MD) simulations. Results We observed that hesperetin interacts with different types of proteins involving hydrogen bonds, pi-pi effects, pi-cation bonding and pi-sigma interactions with varying binding energies. Among all five tested proteins, our compound has the highest binding affinity with 3GPG at −8.5 kcal/mol. The ligand used in this study also matches the Lipinski’s rule of five in addition to exhibiting closely similar properties with that of

  4. Mechanism and role of MCP-1 upregulation upon chikungunya virus infection in human peripheral blood mononuclear cells

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    Ruiz Silva, Mariana; van der Ende-Metselaar, Heidi; Mulder, H. Lie; Smit, Jolanda M.; Rodenhuis-Zybert, Izabela A.

    2016-01-01

    Monocyte chemoattractant protein-1 (MCP-1/CCL2)-mediated migration of monocytes is essential for immunological surveillance of tissues. During chikungunya virus (CHIKV) infection however, excessive production of MCP-1 has been linked to disease pathogenesis. High MCP-1 serum levels are detected during the viremic phase of CHIKV infection and correlate with the virus titre. In vitro CHIKV infection was also shown to stimulate MCP-1 production in whole blood; yet the role and the mechanism of MCP-1 production upon infection of human peripheral blood mononuclear cells remain unknown. Here we found that active CHIKV infection stimulated production of MCP-1 in monocytes. Importantly however, we found that communication with other leukocytes is crucial to yield MCP-1 by monocytes upon CHIKV infection. Indeed, blocking interferon-α/β receptor or the JAK1/JAK2 signalling downstream of the receptor abolished CHIKV-mediated MCP-1 production. Additionally, we show that despite the apparent correlation between IFN type I, CHIKV replication and MCP-1, modulating the levels of the chemokine did not influence CHIKV infection. In summary, our data disclose the complexity of MCP-1 regulation upon CHIKV infection and point to a crucial role of IFNβ in the chemokine secretion. We propose that balance between these soluble factors is imperative for an appropriate host response to CHIKV infection. PMID:27558873

  5. Mechanism and role of MCP-1 upregulation upon chikungunya virus infection in human peripheral blood mononuclear cells.

    Science.gov (United States)

    Ruiz Silva, Mariana; van der Ende-Metselaar, Heidi; Mulder, H Lie; Smit, Jolanda M; Rodenhuis-Zybert, Izabela A

    2016-01-01

    Monocyte chemoattractant protein-1 (MCP-1/CCL2)-mediated migration of monocytes is essential for immunological surveillance of tissues. During chikungunya virus (CHIKV) infection however, excessive production of MCP-1 has been linked to disease pathogenesis. High MCP-1 serum levels are detected during the viremic phase of CHIKV infection and correlate with the virus titre. In vitro CHIKV infection was also shown to stimulate MCP-1 production in whole blood; yet the role and the mechanism of MCP-1 production upon infection of human peripheral blood mononuclear cells remain unknown. Here we found that active CHIKV infection stimulated production of MCP-1 in monocytes. Importantly however, we found that communication with other leukocytes is crucial to yield MCP-1 by monocytes upon CHIKV infection. Indeed, blocking interferon-α/β receptor or the JAK1/JAK2 signalling downstream of the receptor abolished CHIKV-mediated MCP-1 production. Additionally, we show that despite the apparent correlation between IFN type I, CHIKV replication and MCP-1, modulating the levels of the chemokine did not influence CHIKV infection. In summary, our data disclose the complexity of MCP-1 regulation upon CHIKV infection and point to a crucial role of IFNβ in the chemokine secretion. We propose that balance between these soluble factors is imperative for an appropriate host response to CHIKV infection. PMID:27558873

  6. Human keratinocytes restrict chikungunya virus replication at a post-fusion step

    Energy Technology Data Exchange (ETDEWEB)

    Bernard, Eric [Centre d' étude d’agents Pathogènes et Biotechnologies pour la Santé, CPBS CNRS- UMR5236/UM1/UM2, Montpellier (France); Hamel, Rodolphe [Laboratoire Maladies Infectieuses et Vecteurs: Ecologie, Génétique, Evolution, Contrôle, UMR 5290 CNRS/IRD/UM1, Montpellier (France); Neyret, Aymeric [Centre d' étude d’agents Pathogènes et Biotechnologies pour la Santé, CPBS CNRS- UMR5236/UM1/UM2, Montpellier (France); Ekchariyawat, Peeraya [Laboratoire Maladies Infectieuses et Vecteurs: Ecologie, Génétique, Evolution, Contrôle, UMR 5290 CNRS/IRD/UM1, Montpellier (France); Molès, Jean-Pierre [INSERM U1058, UM1, CHU Montpellier (France); Simmons, Graham [Blood Systems Research Institute, San Francisco, CA 94118 (United States); Chazal, Nathalie [Centre d' étude d’agents Pathogènes et Biotechnologies pour la Santé, CPBS CNRS- UMR5236/UM1/UM2, Montpellier (France); Desprès, Philippe [Unité Interactions Moléculaires Flavivirus-Hôtes, Institut Pasteur, Paris (France); and others

    2015-02-15

    Transmission of chikungunya virus (CHIKV) to humans is initiated by puncture of the skin by a blood-feeding Aedes mosquito. Despite the growing knowledge accumulated on CHIKV, the interplay between skin cells and CHIKV following inoculation still remains unclear. In this study we questioned the behavior of human keratinocytes, the predominant cell population in the skin, following viral challenge. We report that CHIKV rapidly elicits an innate immune response in these cells leading to the enhanced transcription of type I/II and type III interferon genes. Concomitantly, we show that despite viral particles internalization into Rab5-positive endosomes and efficient fusion of virus and cell membranes, keratinocytes poorly replicate CHIKV as attested by absence of nonstructural proteins and genomic RNA synthesis. Accordingly, human keratinocytes behave as an antiviral defense against CHIKV infection rather than as a primary targets for initial replication. This picture significantly differs from that reported for Dengue and West Nile mosquito-borne viruses. - Highlights: • Human keratinocytes support endocytosis of CHIKV and fusion of viral membranes. • CHIKV replication is blocked at a post entry step in these cells. • Infection upregulates type-I, –II and –III IFN genes expression. • Keratinocytes behave as immune sentinels against CHIKV.

  7. Chikungunya virus and Aedes mosquitoes: saliva is infectious as soon as two days after oral infection.

    Directory of Open Access Journals (Sweden)

    Mathieu Dubrulle

    Full Text Available BACKGROUND: Aedes aegypti and Aedes albopictus are potential vectors of chikungunya virus (CHIKV. The recent CHIKV outbreaks were caused by a new variant characterized by a mutation in the E1 glycoprotein gene (E1-226V which has favored a better transmissibility by Ae. albopictus. As Ae. albopictus tends to replace Ae. aegypti in many regions, one question remained: is Ae. albopictus as efficient as Ae. aegypti to transmit the variant E1-226V of CHIKV? METHODOLOGY AND FINDINGS: We infected orally both species with the variant E1-226V and estimated the infection, the viral dissemination, and the transmission rate by real time RT-PCR. Additionally, we used an in vitro assay to determine the amount of virus delivered by mosquitoes in their saliva. We found that Ae. aegypti as well as Ae. albopictus ensured a high replication of the virus which underwent an efficient dissemination as detectable in the salivary glands at day 2 post-infection (pi. Infectious CHIKV particles were delivered by salivary glands from day 2 with a maximum at day 6 pi for Ae. albopictus (10(3.3 PFU and day 7 pi for Ae. aegypti (10(2.5 PFU. CONCLUSIONS: Ae. albopictus is slightly more efficient than Ae. aegypti to transmit the variant E1-226V of CHIKV. These results will help to design an efficient vector control to limit transmission as soon as the first human cases are diagnosed.

  8. Human keratinocytes restrict chikungunya virus replication at a post-fusion step

    International Nuclear Information System (INIS)

    Transmission of chikungunya virus (CHIKV) to humans is initiated by puncture of the skin by a blood-feeding Aedes mosquito. Despite the growing knowledge accumulated on CHIKV, the interplay between skin cells and CHIKV following inoculation still remains unclear. In this study we questioned the behavior of human keratinocytes, the predominant cell population in the skin, following viral challenge. We report that CHIKV rapidly elicits an innate immune response in these cells leading to the enhanced transcription of type I/II and type III interferon genes. Concomitantly, we show that despite viral particles internalization into Rab5-positive endosomes and efficient fusion of virus and cell membranes, keratinocytes poorly replicate CHIKV as attested by absence of nonstructural proteins and genomic RNA synthesis. Accordingly, human keratinocytes behave as an antiviral defense against CHIKV infection rather than as a primary targets for initial replication. This picture significantly differs from that reported for Dengue and West Nile mosquito-borne viruses. - Highlights: • Human keratinocytes support endocytosis of CHIKV and fusion of viral membranes. • CHIKV replication is blocked at a post entry step in these cells. • Infection upregulates type-I, –II and –III IFN genes expression. • Keratinocytes behave as immune sentinels against CHIKV

  9. That Which Bends Up: A Case Report and Literature Review of Chikungunya Virus.

    Science.gov (United States)

    Peper, Shana M; Monson, Benjamin J; Van Schooneveld, Trevor; Smith, Christopher J

    2016-05-01

    We present a case of chikungunya virus (CHIKV) in a 39-year-old female who developed an acute febrile illness marked by polyarthralgia and rash after returning from Saint Lucia. This epidemic-prone pathogen is increasingly likely to be encountered by primary care and hospital physicians in the coming months. The virus was first locally transmitted in the Caribbean in December 2013 and has since spread to 44 countries and 47 US states, affecting a suspected 1.2 million people. A mosquito-borne virus, CHIKV causes a severe and symmetric polyarthralgia that can relapse for months to years, creating debilitating illness and profound socioeconomic consequences. Current treatment is limited to supportive measures, which are dependent on nonsteroidal anti-inflammatory drugs. Research into immunomodulatory agents, antiviral therapies, and vaccines is ongoing. Prevention remains key in slowing the spread of disease. Patient education should focus on personal protective measures, such as insect repellant and remaining indoors, while public health departments should implement strategies to control vector breeding grounds. Given the possibility of relapsing and debilitating disease, general internists should consider CHIKV in the differential diagnosis of a returning traveler with acute onset of fever, polyarthralgia, and rash.

  10. Host Alternation of Chikungunya Virus Increases Fitness while Restricting Population Diversity and Adaptability to Novel Selective Pressures

    OpenAIRE

    Coffey, L. L.; Vignuzzi, M.

    2011-01-01

    The mechanisms by which RNA arboviruses, including chikungunya virus (CHIKV), evolve and maintain the ability to infect vertebrate and invertebrate hosts are poorly understood. To understand how host specificity shapes arbovirus populations, we studied CHIKV populations passaged alternately between invertebrate and vertebrate cells (invertebrate ↔ vertebrate) to simulate natural alternation and contrasted the results with those for populations that were artificially released from cycling by p...

  11. Molecular investigations of chikungunya virus during outbreaks in Orissa, Eastern India in 2010.

    Science.gov (United States)

    Das, Biswadeep; Sahu, Abhipsa; Das, Mumani; Patra, Aparna; Dwibedi, Bhagirathi; Kar, Santanu K; Hazra, Rupenangshu K

    2012-07-01

    Chikungunya virus (CHIKV), an arthritogenic alphavirus, is transmitted to humans by mosquitoes of genus Aedes, mainly Aedes aegypti and Aedes albopictus. The resurgence of CHIKV in different parts of India is a point of major public health concern. In 2010, chikungunya outbreaks with high epidemic magnitude were recorded in coastal areas of Orissa, Eastern India, affecting more than 15,000 people coupled with severe arthralgia and prolonged morbidites. Detailed entomological, serological and molecular investigation of this unprecendented outbreak was carried out by collecting and studying 1359 mosquito samples belonging to A. albopictus, A. aegypti, A. vittatus, A. edwardsii and Culex species and 220 patients serum from the affected areas. In this study, CHIKV specific IgM capture-ELISA and reverse-transcription PCR (RT-PCR) were done to detect recent infection of CHIKV in serum samples and adult mosquitoes collected from the affected areas. The high maximum likelihood estimate (MLE) (15.2) in A. albopictus mosquitoes indicated that it was the principal vector involved in transmission of CHIKV in Orissa. Phylogenetic analysis revealed that the CHIKV strains involved in the outbreak belonged to the Indian Ocean Lineage (IOL) group within the East, Central and South African (ECSA) genotype. Genetic characterization of envelope glycoprotein (E1 and E2) genes revealed that all the CHIKV isolates from Orissa had the E1-A226V mutation that enhances viral dissemination and transmissibility by A. albopictus mosquitoes along with E2-L210Q and E2-I211T mutations, which play an epistatic role with E1-A226V mutation in adaptation of CHIKV to A. albopictus by increasing its midgut infectivity, thereby favoring its vectorial capacity. Our results showed the involvement of A. albopictus vector in the recent outbreaks in Orissa and circulation of IOL strains of ECSA genotype of CHIKV with E1-A226V, E2-L210Q and E2-I211T mutations in vectors and patients serum. PMID:22484761

  12. Copy number variation of Chikungunya ECSA virus with disease symptoms among Indian patients.

    Science.gov (United States)

    Dutta, Sudip Kumar; Pal, Tithi; Saha, Bibhuti; Mandal, Syamsundar; Tripathi, Anusri

    2014-08-01

    After a gap of three decades, from 2005 onwards, a series of Chikungunya virus (CHIKV) outbreaks occurred worldwide. This study was performed to detect CHIKV infection, its genotype among symptomatic Eastern Indian patients and to analyze any association between the presence of CHIKV genome in patient body with appearance of disease symptoms (n = 199). Plasma-extracted viral RNA was reverse transcribed to cDNA and PCR-amplified followed by agarose gel electrophoresis. Viral load among CHIKV-positive patients was determined by real time RT-PCR. CHIKV-IgM in sera was detected by ELISA. Sequencing and phylogenetic analysis of plasma-extracted PCR products was done. CHIKV genome and IgM were detected among 65.3% (n = 130) and 41.2% (n = 82) patients respectively. Joint swelling was significantly associated with CHIKV infection (P-value: 0.0003). CHIKV PCR positive patients were grouped in two categories: Group-I: viral load patients clustered in Group-II. Fever and joint swelling were significantly more prevalent among Group-II patients, whereas rash and diarrhoea among Group-I patients (P-value Patient-isolated CHIKV sequences clustered with CHIKV ECSA genotypes in the phylogenetic tree, with two types of CHIKV strains found to circulate among them-as indicated by their different nucleotide sequences. This is the first study detecting the presence of CHIKV ECSA genotype among Eastern Indian patients. Fever and joint swelling might have appeared first followed by rash, diarrhea during disease progression-as indicated by CHIK viral load in patients. Thus, viral load can be used as unique diagnostic and prognostic marker of Chikungunya disease pathogenesis. PMID:24132555

  13. Sequential adaptive mutations enhance efficient vector switching by Chikungunya virus and its epidemic emergence.

    Directory of Open Access Journals (Sweden)

    Konstantin A Tsetsarkin

    2011-12-01

    Full Text Available The adaptation of Chikungunya virus (CHIKV to a new vector, the Aedes albopictus mosquito, is a major factor contributing to its ongoing re-emergence in a series of large-scale epidemics of arthritic disease in many parts of the world since 2004. Although the initial step of CHIKV adaptation to A. albopictus was determined to involve an A226V amino acid substitution in the E1 envelope glycoprotein that first arose in 2005, little attention has been paid to subsequent CHIKV evolution after this adaptive mutation was convergently selected in several geographic locations. To determine whether selection of second-step adaptive mutations in CHIKV or other arthropod-borne viruses occurs in nature, we tested the effect of an additional envelope glycoprotein amino acid change identified in Kerala, India in 2009. This substitution, E2-L210Q, caused a significant increase in the ability of CHIKV to develop a disseminated infection in A. albopictus, but had no effect on CHIKV fitness in the alternative mosquito vector, A. aegypti, or in vertebrate cell lines. Using infectious viruses or virus-like replicon particles expressing the E2-210Q and E2-210L residues, we determined that E2-L210Q acts primarily at the level of infection of A. albopictus midgut epithelial cells. In addition, we observed that the initial adaptive substitution, E1-A226V, had a significantly stronger effect on CHIKV fitness in A. albopictus than E2-L210Q, thus explaining the observed time differences required for selective sweeps of these mutations in nature. These results indicate that the continuous CHIKV circulation in an A. albopictus-human cycle since 2005 has resulted in the selection of an additional, second-step mutation that may facilitate even more efficient virus circulation and persistence in endemic areas, further increasing the risk of more severe and expanded CHIK epidemics.

  14. Sequential adaptive mutations enhance efficient vector switching by Chikungunya virus and its epidemic emergence.

    Science.gov (United States)

    Tsetsarkin, Konstantin A; Weaver, Scott C

    2011-12-01

    The adaptation of Chikungunya virus (CHIKV) to a new vector, the Aedes albopictus mosquito, is a major factor contributing to its ongoing re-emergence in a series of large-scale epidemics of arthritic disease in many parts of the world since 2004. Although the initial step of CHIKV adaptation to A. albopictus was determined to involve an A226V amino acid substitution in the E1 envelope glycoprotein that first arose in 2005, little attention has been paid to subsequent CHIKV evolution after this adaptive mutation was convergently selected in several geographic locations. To determine whether selection of second-step adaptive mutations in CHIKV or other arthropod-borne viruses occurs in nature, we tested the effect of an additional envelope glycoprotein amino acid change identified in Kerala, India in 2009. This substitution, E2-L210Q, caused a significant increase in the ability of CHIKV to develop a disseminated infection in A. albopictus, but had no effect on CHIKV fitness in the alternative mosquito vector, A. aegypti, or in vertebrate cell lines. Using infectious viruses or virus-like replicon particles expressing the E2-210Q and E2-210L residues, we determined that E2-L210Q acts primarily at the level of infection of A. albopictus midgut epithelial cells. In addition, we observed that the initial adaptive substitution, E1-A226V, had a significantly stronger effect on CHIKV fitness in A. albopictus than E2-L210Q, thus explaining the observed time differences required for selective sweeps of these mutations in nature. These results indicate that the continuous CHIKV circulation in an A. albopictus-human cycle since 2005 has resulted in the selection of an additional, second-step mutation that may facilitate even more efficient virus circulation and persistence in endemic areas, further increasing the risk of more severe and expanded CHIK epidemics. PMID:22174678

  15. Seroprevalence of Infections with Dengue, Rift Valley Fever and Chikungunya Viruses in Kenya, 2007.

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    Caroline Ochieng

    Full Text Available Arthropod-borne viruses are a major constituent of emerging infectious diseases worldwide, but limited data are available on the prevalence, distribution, and risk factors for transmission in Kenya and East Africa. In this study, we used 1,091 HIV-negative blood specimens from the 2007 Kenya AIDS Indicator Survey (KAIS 2007 to test for the presence of IgG antibodies to dengue virus (DENV, chikungunya virus (CHIKV and Rift Valley fever virus (RVFV.The KAIS 2007 was a national population-based survey conducted by the Government of Kenya to provide comprehensive information needed to address the HIV/AIDS epidemic. Antibody testing for arboviruses was performed on stored blood specimens from KAIS 2007 through a two-step sandwich IgG ELISA using either commercially available kits or CDC-developed assays. Out of the 1,091 samples tested, 210 (19.2% were positive for IgG antibodies against at least one of the three arboviruses. DENV was the most common of the three viruses tested (12.5% positive, followed by RVFV and CHIKV (4.5% and 0.97%, respectively. For DENV and RVFV, the participant's province of residence was significantly associated (P≤.01 with seropositivity. Seroprevalence of DENV and RVFV increased with age, while there was no correlation between province of residence/age and seropositivity for CHIKV. Females had twelve times higher odds of exposure to CHIK as opposed to DENV and RVFV where both males and females had the same odds of exposure. Lack of education was significantly associated with a higher odds of previous infection with either DENV or RVFV (p <0.01. These data show that a number of people are at risk of arbovirus infections depending on their geographic location in Kenya and transmission of these pathogens is greater than previously appreciated. This poses a public health risk, especially for DENV.

  16. Native Wolbachia from Aedes albopictus Blocks Chikungunya Virus Infection In Cellulo.

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    Vincent Raquin

    Full Text Available Wolbachia, a widespread endosymbiont of terrestrial arthropods, can protect its host against viral and parasitic infections, a phenotype called "pathogen blocking". However, in some cases Wolbachia may have no effect or even enhance pathogen infection, depending on the host-Wolbachia-pathogen combination. The tiger mosquito Aedes albopictus is naturally infected by two strains of Wolbachia, wAlbA and wAlbB, and is a competent vector for different arboviruses such as dengue virus (DENV and chikungunya virus (CHIKV. Interestingly, it was shown in some cases that Ae. albopictus native Wolbachia strains are able to inhibit DENV transmission by limiting viral replication in salivary glands, but no such impact was measured on CHIKV replication in vivo. To better understand the Wolbachia/CHIKV/Ae. albopictus interaction, we generated a cellular model using Ae. albopictus derived C6/36 cells that we infected with the wAlbB strain. Our results indicate that CHIKV infection is negatively impacted at both RNA replication and virus assembly/secretion steps in presence of wAlbB. Using FISH, we observed CHIKV and wAlbB in the same mosquito cells, indicating that the virus is still able to enter the cell in the presence of the bacterium. Further work is needed to decipher molecular pathways involved in Wolbachia-CHIKV interaction at the cellular level, but this cellular model can be a useful tool to study the mechanism behind virus blocking phenotype induced by Wolbachia. More broadly, this put into question the ecological role of Wolbachia symbiont in Ae. albopictus, but also the ability of the CHIKV to counteract Wolbachia's antiviral potential in vivo.

  17. Viremia in North American Mammals and Birds After Experimental Infection with Chikungunya Viruses.

    Science.gov (United States)

    Bosco-Lauth, Angela M; Nemeth, Nicole M; Kohler, Dennis J; Bowen, Richard A

    2016-03-01

    Chikungunya virus (CHIKV) is an arthropod-borne virus, which is known to cause severe disease only in humans. To investigate its potential zoonotic host range and evaluate reservoir competence among these hosts, experimental infections were performed on individuals from nine avian and 12 mammalian species representing both domestic and wild animals common to North America. Hamsters and inbred mice have previously been shown to develop viremia after inoculation with CHIKV and were used as positive controls for infection. Aside from big brown bats (Eptesicus fuscus), none of the mammals or birds developed detectable viremia or overt clinical disease. However, most mammals and a smaller proportion of birds developed neutralizing antibody responses to CHIKV. On the basis of these results, it seems unlikely that CHIKV poses a significant health threat to most domestic animals or wildlife and that the species examined do not likely contribute to natural transmission cycles. Additional studies should further evaluate bats and wild rodents as potential reservoir hosts for CHIKV transmission during human epidemics.

  18. Temporal SILAC-based quantitative proteomics identifies host factors involved in chikungunya virus replication.

    Science.gov (United States)

    Treffers, Emmely E; Tas, Ali; Scholte, Florine E M; Van, Myrthe N; Heemskerk, Matthias T; de Ru, Arnoud H; Snijder, Eric J; van Hemert, Martijn J; van Veelen, Peter A

    2015-07-01

    Chikungunya virus (CHIKV) is an arthropod-borne reemerging human pathogen that generally causes a severe persisting arthritis. Since 2005, the virus has infected millions of people during outbreaks in Africa, Indian Ocean Islands, Asia, and South/Central America. Many steps of the replication and expression of CHIKV's 12-kb RNA genome are highly dependent on cellular factors, which thus constitute potential therapeutic targets. SILAC and LC-MS/MS were used to define the temporal dynamics of the cellular response to infection. Using samples harvested at 8, 10, and 12 h postinfection, over 4700 proteins were identified and per time point 2800-3500 proteins could be quantified in both biological replicates. At 8, 10, and 12 h postinfection, 13, 38, and 106 proteins, respectively, were differentially expressed. The majority of these proteins showed decreased abundance. Most subunits of the RNA polymerase II complex were progressively degraded, which likely contributes to the transcriptional host shut-off observed during CHIKV infection. Overexpression of four proteins that were significantly downregulated (Rho family GTPase 3 (Rnd3), DEAD box helicase 56 (DDX56), polo-like kinase 1 (Plk1), and ubiquitin-conjugating enzyme E2C (UbcH10) reduced susceptibility of cells to CHIKV infection, suggesting that infection-induced downregulation of these proteins is beneficial for CHIKV replication. All MS data have been deposited in the ProteomeXchange with identifier PXD001330 (http://proteomecentral.proteomexchange.org/dataset/PXD001330).

  19. Viremia in North American Mammals and Birds After Experimental Infection with Chikungunya Viruses.

    Science.gov (United States)

    Bosco-Lauth, Angela M; Nemeth, Nicole M; Kohler, Dennis J; Bowen, Richard A

    2016-03-01

    Chikungunya virus (CHIKV) is an arthropod-borne virus, which is known to cause severe disease only in humans. To investigate its potential zoonotic host range and evaluate reservoir competence among these hosts, experimental infections were performed on individuals from nine avian and 12 mammalian species representing both domestic and wild animals common to North America. Hamsters and inbred mice have previously been shown to develop viremia after inoculation with CHIKV and were used as positive controls for infection. Aside from big brown bats (Eptesicus fuscus), none of the mammals or birds developed detectable viremia or overt clinical disease. However, most mammals and a smaller proportion of birds developed neutralizing antibody responses to CHIKV. On the basis of these results, it seems unlikely that CHIKV poses a significant health threat to most domestic animals or wildlife and that the species examined do not likely contribute to natural transmission cycles. Additional studies should further evaluate bats and wild rodents as potential reservoir hosts for CHIKV transmission during human epidemics. PMID:26666699

  20. Application of GelC-MS/MS to Proteomic Profiling of Chikungunya Virus Infection: Preparation of Peptides for Analysis.

    Science.gov (United States)

    Paemanee, Atchara; Wikan, Nitwara; Roytrakul, Sittiruk; Smith, Duncan R

    2016-01-01

    Gel-enhanced liquid chromatography coupled with tandem mass spectrometry (GeLC-MS/MS) is a labor intensive, but relatively straightforward methodology that generates high proteome coverage which can be applied to the proteome analysis of a range of starting materials such as cells or patient specimens. Sample proteins are resolved electrophoretically in one dimension through a sodium dodecyl sulfate (SDS) polyacrylamide gel after which the lanes are sliced into sections. The sections are further diced and the gel cubes generated are subjected to in-gel tryptic digestion. The resultant peptides can then be analyzed by tandem mass spectroscopy to identify the proteins by database searching. The methodology can routinely detect several thousand proteins in one analysis. The protocol we describe here has been used with both cells in culture that have been infected with chikungunya virus and specimens from Chikungunya fever patients. This protocol details the process for generating peptides for subsequent mass spectroscopic and bioinformatic analysis. PMID:27233271

  1. Development and Validation of a Quantitative, One-Step, Multiplex, Real-Time Reverse Transcriptase PCR Assay for Detection of Dengue and Chikungunya Viruses.

    Science.gov (United States)

    Simmons, Monika; Myers, Todd; Guevara, Carolina; Jungkind, Donald; Williams, Maya; Houng, Huo-Shu

    2016-07-01

    Dengue virus (DENV) and chikungunya virus (CHIKV) are important human pathogens with common transmission vectors and similar clinical presentations. Patient care may be impacted by the misdiagnosis of DENV and CHIKV in areas where both viruses cocirculate. In this study, we have developed and validated a one-step multiplex reverse transcriptase PCR (RT-PCR) to simultaneously detect, quantify, and differentiate between four DENV serotypes (pan-DENV) and chikungunya virus. The assay uses TaqMan technology, employing two forward primers, three reverse primers, and four fluorophore-labeled probes in a single-reaction format. Coextracted and coamplified RNA was used as an internal control (IC), and in vitro-transcribed DENV and CHIKV RNAs were used to generate standard curves for absolute quantification. The diagnostic 95% limits of detection (LOD) within the linear range were 50 and 60 RNA copies/reaction for DENV (serotypes 1 to 4) and CHIKV, respectively. Our assay was able to detect 53 different strains of DENV, representing four serotypes, and six strains of CHIKV. No cross-reactivity was observed with related flaviviruses and alphaviruses, To evaluate diagnostic sensitivity and specificity, 89 clinical samples positive or negative for DENV (serotypes 1 to 4) and CHIKV by the standard virus isolation method were tested in our assay. The multiplex RT-PCR assay showed 95% sensitivity and 100% specificity for DENV and 100% sensitivity and specificity for CHIKV. With an assay turnaround time of less than 2 h, including extraction of RNA, the multiplex quantitative RT-PCR assay provides rapid diagnosis for the differential detection of two clinically indistinguishable diseases, whose geographical occurrence is increasingly overlapping. PMID:27098955

  2. High efficiency of temperate Aedes albopictus to transmit chikungunya and dengue viruses in the Southeast of France.

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    Anubis Vega-Rua

    Full Text Available BACKGROUND: Since 2005, cases of chikungunya (CHIK were caused by an unusual vector, Aedes albopictus. This mosquito, present in Europe since 1979, has gained importance since its involvement in the first CHIK outbreak in Italy in 2007. The species is capable of transmitting experimentally 26 arboviruses. However, the vectorial status of its temperate populations has remained little investigated. In 2010, autochthonous cases of CHIK and dengue (DEN were reported in southeastern France. We evaluated the potential of a French population of Ae. albopictus in the transmission of both viruses. METHODOLOGY AND PRINCIPAL FINDINGS: We used two strains of each virus, CHIK AND DEN: one strain was isolated from an imported case, and one from an autochthonous case. We used as controls Aedes aegypti from India and Martinique, the source of the imported cases of CHIK and DEN, respectively. We showed that Ae. albopictus from Cagnes-sur-Mer (AL-CSM was as efficient as the typical tropical vector Ae. aegypti from India to experimentally transmit both CHIK strains isolated from patients in Fréjus, with around 35-67% of mosquitoes delivering up to 14 viral particles at day 3 post-infection (pi. The unexpected finding came from the high efficiency of AL-CSM to transmit both strains of DENV-1 isolated from patients in Nice. Almost 67% of Ae. albopictus AL-CSM which have ensured viral dissemination were able to transmit at day 9 pi when less than 21% of the typical DEN vector Ae. aegypti from Martinique could achieve transmission. CONCLUSIONS/SIGNIFICANCE: Temperate Ae. albopictus behaves differently compared to its counterpart from tropical regions, where recurrent epidemic outbreaks occur. Its potential responsibility for outbreaks in Europe should not be minimized.

  3. Epistatic roles of E2 glycoprotein mutations in adaption of chikungunya virus to Aedes albopictus and Ae. aegypti mosquitoes.

    Directory of Open Access Journals (Sweden)

    Konstantin A Tsetsarkin

    Full Text Available Between 2005 and 2007 Chikungunya virus (CHIKV caused its largest outbreak/epidemic in documented history. An unusual feature of this epidemic is the involvement of Ae. albopictus as a principal vector. Previously we have demonstrated that a single mutation E1-A226V significantly changed the ability of the virus to infect and be transmitted by this vector when expressed in the background of well characterized CHIKV strains LR2006 OPY1 and 37997. However, in the current study we demonstrate that introduction of the E1-A226V mutation into the background of an infectious clone derived from the Ag41855 strain (isolated in Uganda in 1982 does not significantly increase infectivity for Ae. albopictus. In order to elucidate the genetic determinants that affect CHIKV sensitivity to the E1-A226V mutation in Ae. albopictus, the genomes of the LR2006 OPY1 and Ag41855 strains were used for construction of chimeric viruses and viruses with a specific combination of point mutations at selected positions. Based upon the midgut infection rates of the derived viruses in Ae. albopictus and Ae. aegypti mosquitoes, a critical role of the mutations at positions E2-60 and E2-211 on vector infection was revealed. The E2-G60D mutation was an important determinant of CHIKV infectivity for both Ae. albopictus and Ae. aegypti, but only moderately modulated the effect of the E1-A226V mutation in Ae. albopictus. However, the effect of the E2-I211T mutation with respect to mosquito infections was much more specific, strongly modifying the effect of the E1-A226V mutation in Ae. albopictus. In contrast, CHIKV infectivity for Ae. aegypti was not influenced by the E2-1211T mutation. The occurrence of the E2-60G and E2-211I residues among CHIKV isolates was analyzed, revealing a high prevalence of E2-211I among strains belonging to the Eastern/Central/South African (ECSA clade. This suggests that the E2-211I might be important for adaptation of CHIKV to some particular conditions

  4. Endocytosis of chikungunya virus into mammalian cells: role of clathrin and early endosomal compartments.

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    Eric Bernard

    Full Text Available BACKGROUND: The replicative cycle of chikungunya virus (CHIKV, an alphavirus that recently re-emerged in India and in Indian Ocean area, remains mostly unknown. The aim of the present study was to investigate the intracellular trafficking pathway(s hijacked by CHIKV to enter mammalian cells. METHODOLOGY/PRINCIPAL FINDINGS: Entry pathways were investigated using a variety of pharmacological inhibitors or overexpression of dominant negative forms of proteins perturbating cellular endocytosis. We found that CHIKV infection of HEK293T mammalian cells is independent of clathrin heavy chain and- dependent of functional Eps15, and requires integrity of Rab5-, but not Rab7-positive endosomal compartment. Cytoskeleton integrity is crucial as cytochalasin D and nocodazole significantly reduced infection of the cells. Finally, both methyl beta-cyclodextrin and lysomotropic agents impaired CHIKV infection, supporting that a cholesterol-, pH-dependent step is required to achieve productive infection. Interestingly, differential sensitivity to lysomotropic agents was observed between the prototypal 37997 African strain of CHIKV and the LR-OPY1 virus isolated from the recent outbreak in Reunion Island. CONCLUSIONS: Together our data indicate that CHIKV entry in its target cells is essentially mediated by clathrin-independent, Eps15-dependent endocytosis. Despite that this property is shared by the prototypal 37997 African strain of CHIKV and the LR-OPY1 virus isolated from the recent outbreak in La Réunion Island, differential sensitivity to lysomotropic agents may support that the LR-OPY1 strain has acquired specific entry mechanisms.

  5. Antiviral Hammerhead Ribozymes Are Effective for Developing Transgenic Suppression of Chikungunya Virus in Aedes aegypti Mosquitoes.

    Science.gov (United States)

    Mishra, Priya; Furey, Colleen; Balaraman, Velmurugan; Fraser, Malcolm J

    2016-01-01

    The chikungunya virus (CHIKV) is an emerging pathogen with widespread distribution in regions of Africa, India, and Asia that threatens to spread into temperate climates with the introduction of its major vector, Aedes albopictus. CHIKV causes a disease frequently misdiagnosed as dengue fever, with potentially life-threatening symptoms that can result in a longer-term debilitating arthritis. The increasing risk of spread from endemic regions via human travel and commerce and the current absence of a vaccine put a significant proportion of the world population at risk for this disease. In this study we designed and tested hammerhead ribozymes (hRzs) targeting CHIKV structural protein genes of the RNA genome as potential antivirals both at the cellular and in vivo level. We employed the CHIKV strain 181/25, which exhibits similar infectivity rates in both Vero cell cultures and mosquitoes. Virus suppression assay performed on transformed Vero cell clones of all seven hRzs demonstrated that all are effective at inhibiting CHIKV in Vero cells, with hRz #9 and #14 being the most effective. piggyBac transformation vectors were constructed using the Ae. aegypti t-RNA(val) Pol III promoted hRz #9 and #14 effector genes to establish a total of nine unique transgenic Higgs White Eye (HWE) Ae. aegypti lines. Following confirmation of transgene expression by real-time polymerase chain reaction (RT-PCR), comparative TCID50-IFA analysis, in situ Immuno-fluorescent Assays (IFA) and analysis of salivary CHIKV titers demonstrated effective suppression of virus replication at 7 dpi in heterozygous females of each of these transgenic lines compared with control HWE mosquitoes. This report provides a proof that appropriately engineered hRzs are powerful antiviral effector genes suitable for population replacement strategies. PMID:27294950

  6. Chikungunya virus fusion properties elucidated by single-particle and bulk approaches.

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    van Duijl-Richter, Mareike K S; Blijleven, Jelle S; van Oijen, Antoine M; Smit, Jolanda M

    2015-08-01

    Chikungunya virus (CHIKV) is a rapidly spreading, enveloped alphavirus causing fever, rash and debilitating polyarthritis. No specific treatment or vaccines are available to treat or prevent infection. For the rational design of vaccines and antiviral drugs, it is imperative to understand the molecular mechanisms involved in CHIKV infection. A critical step in the life cycle of CHIKV is fusion of the viral membrane with a host cell membrane. Here, we elucidate this process using ensemble-averaging liposome-virus fusion studies, in which the fusion behaviour of a large virus population is measured, and a newly developed microscopy-based single-particle assay, in which the fusion kinetics of an individual particle can be visualised. The combination of these approaches allowed us to obtain detailed insight into the kinetics, lipid dependency and pH dependency of hemifusion. We found that CHIKV fusion is strictly dependent on low pH, with a threshold of pH 6.2 and optimal fusion efficiency below pH 5.6. At this pH, CHIKV fuses rapidly with target membranes, with typically half of the fusion occurring within 2 s after acidification. Cholesterol and sphingomyelin in the target membrane were found to strongly enhance the fusion process. By analysing our single-particle data using kinetic models, we were able to deduce that the number of rate-limiting steps occurring before hemifusion equals about three. To explain these data, we propose a mechanistic model in which multiple E1 fusion trimers are involved in initiating the fusion process.

  7. Genotypic and phenotypic characterization of Chikungunya virus of different genotypes from Malaysia.

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    I-Ching Sam

    Full Text Available BACKGROUND: Mosquito-borne Chikungunya virus (CHIKV has recently re-emerged globally. The epidemic East/Central/South African (ECSA strains have spread for the first time to Asia, which previously only had endemic Asian strains. In Malaysia, the ECSA strain caused an extensive nationwide outbreak in 2008, while the Asian strains only caused limited outbreaks prior to this. To gain insight into these observed epidemiological differences, we compared genotypic and phenotypic characteristics of CHIKV of Asian and ECSA genotypes isolated in Malaysia. METHODS AND FINDINGS: CHIKV of Asian and ECSA genotypes were isolated from patients during outbreaks in Bagan Panchor in 2006, and Johor in 2008. Sequencing of the CHIKV strains revealed 96.8% amino acid similarity, including an unusual 7 residue deletion in the nsP3 protein of the Asian strain. CHIKV replication in cells and Aedes mosquitoes was measured by virus titration. There were no differences in mammalian cell lines. The ECSA strain reached significantly higher titres in Ae. albopictus cells (C6/36. Both CHIKV strains infected Ae. albopictus mosquitoes at a higher rate than Ae. aegypti, but when compared to each other, the ECSA strain had much higher midgut infection and replication, and salivary gland dissemination, while the Asian strain infected Ae. aegypti at higher rates. CONCLUSIONS: The greater ability of the ECSA strain to replicate in Ae. albopictus may explain why it spread far more quickly and extensively in humans in Malaysia than the Asian strain ever did, particularly in rural areas where Ae. albopictus predominates. Intergenotypic genetic differences were found at E1, E2, and nsP3 sites previously reported to be determinants of host adaptability in alphaviruses. Transmission of CHIKV in humans is influenced by virus strain and vector species, which has implications for regions with more than one circulating CHIKV genotype and Aedes species.

  8. Multiple immune factors are involved in controlling acute and chronic chikungunya virus infection.

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    Yee Suan Poo

    2014-12-01

    Full Text Available The recent epidemic of the arthritogenic alphavirus, chikungunya virus (CHIKV has prompted a quest to understand the correlates of protection against virus and disease in order to inform development of new interventions. Herein we highlight the propensity of CHIKV infections to persist long term, both as persistent, steady-state, viraemias in multiple B cell deficient mouse strains, and as persistent RNA (including negative-strand RNA in wild-type mice. The knockout mouse studies provided evidence for a role for T cells (but not NK cells in viraemia suppression, and confirmed the role of T cells in arthritis promotion, with vaccine-induced T cells also shown to be arthritogenic in the absence of antibody responses. However, MHC class II-restricted T cells were not required for production of anti-viral IgG2c responses post CHIKV infection. The anti-viral cytokines, TNF and IFNγ, were persistently elevated in persistently infected B and T cell deficient mice, with adoptive transfer of anti-CHIKV antibodies unable to clear permanently the viraemia from these, or B cell deficient, mice. The NOD background increased viraemia and promoted arthritis, with B, T and NK deficient NOD mice showing high-levels of persistent viraemia and ultimately succumbing to encephalitic disease. In wild-type mice persistent CHIKV RNA and negative strand RNA (detected for up to 100 days post infection was associated with persistence of cellular infiltrates, CHIKV antigen and stimulation of IFNα/β and T cell responses. These studies highlight that, secondary to antibodies, several factors are involved in virus control, and suggest that chronic arthritic disease is a consequence of persistent, replicating and transcriptionally active CHIKV RNA.

  9. Antiviral Hammerhead Ribozymes Are Effective for Developing Transgenic Suppression of Chikungunya Virus in Aedes aegypti Mosquitoes

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    Priya Mishra

    2016-06-01

    Full Text Available The chikungunya virus (CHIKV is an emerging pathogen with widespread distribution in regions of Africa, India, and Asia that threatens to spread into temperate climates with the introduction of its major vector, Aedes albopictus. CHIKV causes a disease frequently misdiagnosed as dengue fever, with potentially life-threatening symptoms that can result in a longer-term debilitating arthritis. The increasing risk of spread from endemic regions via human travel and commerce and the current absence of a vaccine put a significant proportion of the world population at risk for this disease. In this study we designed and tested hammerhead ribozymes (hRzs targeting CHIKV structural protein genes of the RNA genome as potential antivirals both at the cellular and in vivo level. We employed the CHIKV strain 181/25, which exhibits similar infectivity rates in both Vero cell cultures and mosquitoes. Virus suppression assay performed on transformed Vero cell clones of all seven hRzs demonstrated that all are effective at inhibiting CHIKV in Vero cells, with hRz #9 and #14 being the most effective. piggyBac transformation vectors were constructed using the Ae. aegypti t-RNAval Pol III promoted hRz #9 and #14 effector genes to establish a total of nine unique transgenic Higgs White Eye (HWE Ae. aegypti lines. Following confirmation of transgene expression by real-time polymerase chain reaction (RT-PCR, comparative TCID50-IFA analysis, in situ Immuno-fluorescent Assays (IFA and analysis of salivary CHIKV titers demonstrated effective suppression of virus replication at 7 dpi in heterozygous females of each of these transgenic lines compared with control HWE mosquitoes. This report provides a proof that appropriately engineered hRzs are powerful antiviral effector genes suitable for population replacement strategies

  10. Knowledge and use of prevention measures for chikungunya virus among visitors — Virgin Islands National Park, 2015

    Science.gov (United States)

    Cherry, Cara C.; Beer, Karlyn D.; Fulton, Corey; Wong, David; Buttke, Danielle; Staples, J. Erin; Ellis, Esther M.

    2016-01-01

    Summary Background In June 2014, the mosquito-borne chikungunya virus (CHIKV) emerged in the U.S. Virgin Islands (USVI), a location where tourists comprise the majority of the population during peak season (January–April). Limited information is available concerning visitors’ CHIKV awareness and prevention measures. Methods We surveyed a convenience sample of Virgin Islands National Park visitors aged ≥18 years. Respondents completed a questionnaire assessing CHIKV knowledge, attitudes, and practices; health information-seeking practices; and demographics. Results Of 783 persons contacted, 443 (57%) completed the survey. Fewer than half (208/441 [47%]) were aware of CHIKV. During trip preparation, 28% of respondents (126/443) investigated USVI-specific health concerns. Compared with persons unaware of CHIKV, CHIKV-aware persons were more likely to apply insect repellent (134/207 [65%] versus 111/231 [48%]; p < 0.001), wear long-sleeves and long pants (84/203 [41%] versus 57/227 [25%]; p < 0.001), and wear insect repellent-treated clothing (36/204 [18%] versus 22/227 [10%]; p = 0.02). Conclusions The majority of visitors surveyed did not research destination-related health concerns and were unaware of CHIKV. However, CHIKV awareness was associated with using multiple prevention measures to reduce disease risk. These findings underscore the importance of providing tourists with disease education upon destination arrival. PMID:27597388

  11. Chikungunya virus susceptibility & variation in populations of Aedes aegypti (Diptera: Culicidae mosquito from India

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    Mangesh D Gokhale

    2015-01-01

    Full Text Available Background & objectives: Although having immense clinical relevance, yet only a few studies have been targeted to understand the chikungunya virus (CHIKV susceptibility and growth in Aedes aegypti populations from India. This study was undertaken to investigate CHIKV susceptibility and growth kinetics in Ae. aegypti along with genetic heterogeneity of Ae. aegypti populations. Methods: Dose dependent CHIKV susceptibility and growth kinetic studies for three CHIKV strains reported from India were carried out in Ae. aegypti mosquito populations. The phenotypic variation and genetic heterogeneity in five Ae. aegypti populations were investigated using multivariate morphometrics and allozyme variation studies. Results: The dissemination and growth kinetics studies of the three CHIKV strains showed no selective advantage for a particular strain of CHIKV in Ae. aegypti. At 100 per cent infection rate, five geographic Ae. aegypti populations showed differences in dissemination to three CHIKV strains. Morphometric studies revealed phenotypic variation in all the studied populations. The allelic frequencies, F statistics, and Nei′s genetic identity values showed that genetic differences between the populations were small, but significant. Interpretation & conclusions: The results obtained in this study suggest that genetic background of the vector strongly influences the CHIKV susceptibility in Ae. aegypti.

  12. Presence of Autoimmune Antibody in Chikungunya Infection

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    Wirach Maek-a-nantawat

    2009-01-01

    Full Text Available Chikungunya infection has recently re-emerged as an important arthropod-borne disease in Thailand. Recently, Southern Thailand was identified as a potentially endemic area for the chikungunya virus. Here, we report a case of severe musculoskeletal complication, presenting with muscle weakness and swelling of the limbs. During the investigation to exclude autoimmune muscular inflammation, high titers of antinuclear antibody were detected. This is the report of autoimmunity detection associated with an arbovirus infection. The symptoms can mimic autoimmune polymyositis disease, and the condition requires close monitoring before deciding to embark upon prolonged specific treatment with immunomodulators.

  13. Loss of Glycosaminoglycan Receptor Binding after Mosquito Cell Passage Reduces Chikungunya Virus Infectivity.

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    Dhiraj Acharya

    Full Text Available Chikungunya virus (CHIKV is a mosquito-transmitted alphavirus that can cause fever and chronic arthritis in humans. CHIKV that is generated in mosquito or mammalian cells differs in glycosylation patterns of viral proteins, which may affect its replication and virulence. Herein, we compare replication, pathogenicity, and receptor binding of CHIKV generated in Vero cells (mammal or C6/36 cells (mosquito through a single passage. We demonstrate that mosquito cell-derived CHIKV (CHIKV mos has slower replication than mammalian cell-derived CHIKV (CHIKV vero, when tested in both human and murine cell lines. Consistent with this, CHIKV mos infection in both cell lines produce less cytopathic effects and reduced antiviral responses. In addition, infection in mice show that CHIKV mos produces a lower level of viremia and less severe footpad swelling when compared with CHIKV vero. Interestingly, CHIKV mos has impaired ability to bind to glycosaminoglycan (GAG receptors on mammalian cells. However, sequencing analysis shows that this impairment is not due to a mutation in the CHIKV E2 gene, which encodes for the viral receptor binding protein. Moreover, CHIKV mos progenies can regain GAG receptor binding capability and can replicate similarly to CHIKV vero after a single passage in mammalian cells. Furthermore, CHIKV vero and CHIKV mos no longer differ in replication when N-glycosylation of viral proteins was inhibited by growing these viruses in the presence of tunicamycin. Collectively, these results suggest that N-glycosylation of viral proteins within mosquito cells can result in loss of GAG receptor binding capability of CHIKV and reduction of its infectivity in mammalian cells.

  14. Rapid detection and characterization of Chikungunya virus by RT-PCR in febrile patients from Kerala, India.

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    Joseph, Anu Yamuna; Babu, Vidhu Sankar; Dev, Sona S; Gopalakrishnapai, Jayashree; Harish, M; Rajesh, M D; Anisha, S; Mohankumar, C

    2008-08-01

    There has been a resurgence and prevalence of fever with symptoms of Chikungunya (CHIK) and increased death toll in Kerala, the southern-most state of India. The objective of this study was to develop a rapid detection method to determine the presence of CHIK- virus in the serum samples collected from febrile patients in Kerala, India. Serum specimens were analyzed for CHIK viral RNA by RT-PCR using primers specific for nsP1 and E1 genes. Five out of twenty clinical samples were positive for CHIK virus. The partial sequences of the E1 and nsP1 genes of the strain, IndKL01 were highly similar to the Reunion strains and the recently isolated Indian strains. A novel substitution, A148V, was detected in the E1 gene of the isolate, IndKL02. The detection procedure used in this study was simple, sensitive and rapid (less than 4 hr). This result suggests that CHIK viruses similar to the Reunion strains, which had resulted in high morbidity and mortality rates, may have caused the recent Chikungunya outbreak in India. The effect of the variant, E1-A148V, in the virulence and the rate of transmission of the virus deserves further investigation. PMID:18814485

  15. A sensitive epitope-blocking ELISA for the detection of Chikungunya virus-specific antibodies in patients.

    Science.gov (United States)

    Goh, Lucas Y H; Kam, Yiu-Wing; Metz, Stefan W; Hobson-Peters, Jody; Prow, Natalie A; McCarthy, Suzi; Smith, David W; Pijlman, Gorben P; Ng, Lisa F P; Hall, Roy A

    2015-09-15

    Chikungunya fever (CHIKF) has re-emerged as an arboviral disease that mimics clinical symptoms of other diseases such as dengue, malaria, as well as other alphavirus-related illnesses leading to problems with definitive diagnosis of the infection. Herein we describe the development and evaluation of a sensitive epitope-blocking ELISA (EB-ELISA) capable of specifically detecting anti-chikungunya virus (CHIKV) antibodies in clinical samples. The assay uses a monoclonal antibody (mAb) that binds an epitope on the E2 protein of CHIKV and does not exhibit cross-reactivity to other related alphaviruses. We also demonstrated the use of recombinant CHIK virus-like particles (VLPs) as a safe alternative antigen to infectious virions in the assay. Based on testing of 60 serum samples from patients in the acute or convalescent phase of CHIKV infection, the EB-ELISA provided us with 100% sensitivity, and exhibited 98.5% specificity when Ross River virus (RRV)- or Barmah Forest virus (BFV)-immune serum samples were included. This assay meets the public health demands of a rapid, robust, sensitive and specific, yet simple assay for specifically diagnosing CHIK-infections in humans.

  16. [Dengue, Zika and Chikungunya].

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    Kantor, Isabel N

    2016-01-01

    Arboviruses are transmitted by arthropods, including those responsible for the current pandemic: alphavirus (Chikungunya) and flaviviruses (dengue and Zika). Its importance increased in the Americas over the past 20 years. The main vectors are Aedes aegypti and A. albopictus. Dengue infection provides long lasting immunity against the specific serotype and temporary to the other three. Subsequent infection by another serotype determines more serious disease. There is a registered vaccine for dengue, Dengvaxia (Sanofi Pasteur). Other two (Butantan and Takeda) are in Phase III in 2016. Zika infection is usually asymptomatic or occurs with rash, conjunctivitis and not very high fever. There is no vaccine or specific treatment. It can be transmitted by parental, sexual and via blood transfusion. It has been associated with microcephaly. Chikungunya causes prolonged joint pain and persistent immune response. Two candidate vaccines are in Phase II. Dengue direct diagnosis is performed by virus isolation, RT-PCR and ELISA for NS1 antigen detection; indirect methods are ELISA-IgM (cross-reacting with other flavivirus), MAC-ELISA, and plaque neutralization. Zika is diagnosed by RT-PCR and virus isolation. Serological diagnosis cross-reacts with other flavivirus. For CHIKV culture, RT-PCR, MAC-ELISA and plaque neutralization are used. Against Aedes organophosphate larvicides (temephos), organophosphorus insecticides (malathion and fenitrothion) and pyrethroids (permethrin and deltamethrin) are usually employed. Resistance has been described to all these products. Vegetable derivatives are less expensive and biodegradable, including citronella oil, which microencapsulated can be preserved from evaporation.

  17. [Dengue, Zika and Chikungunya].

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    Kantor, Isabel N

    2016-01-01

    Arboviruses are transmitted by arthropods, including those responsible for the current pandemic: alphavirus (Chikungunya) and flaviviruses (dengue and Zika). Its importance increased in the Americas over the past 20 years. The main vectors are Aedes aegypti and A. albopictus. Dengue infection provides long lasting immunity against the specific serotype and temporary to the other three. Subsequent infection by another serotype determines more serious disease. There is a registered vaccine for dengue, Dengvaxia (Sanofi Pasteur). Other two (Butantan and Takeda) are in Phase III in 2016. Zika infection is usually asymptomatic or occurs with rash, conjunctivitis and not very high fever. There is no vaccine or specific treatment. It can be transmitted by parental, sexual and via blood transfusion. It has been associated with microcephaly. Chikungunya causes prolonged joint pain and persistent immune response. Two candidate vaccines are in Phase II. Dengue direct diagnosis is performed by virus isolation, RT-PCR and ELISA for NS1 antigen detection; indirect methods are ELISA-IgM (cross-reacting with other flavivirus), MAC-ELISA, and plaque neutralization. Zika is diagnosed by RT-PCR and virus isolation. Serological diagnosis cross-reacts with other flavivirus. For CHIKV culture, RT-PCR, MAC-ELISA and plaque neutralization are used. Against Aedes organophosphate larvicides (temephos), organophosphorus insecticides (malathion and fenitrothion) and pyrethroids (permethrin and deltamethrin) are usually employed. Resistance has been described to all these products. Vegetable derivatives are less expensive and biodegradable, including citronella oil, which microencapsulated can be preserved from evaporation. PMID:26942903

  18. Chikungunya: epidemiology.

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    Petersen, Lyle R; Powers, Ann M

    2016-01-01

    Chikungunya virus is a mosquito-borne alphavirus that causes fever and debilitating joint pains in humans. Joint pains may last months or years. It is vectored primarily by the tropical and sub-tropical mosquito, Aedes aegypti, but is also found to be transmitted by Aedes albopictus, a mosquito species that can also be found in more temperate climates. In recent years, the virus has risen from relative obscurity to become a global public health menace affecting millions of persons throughout the tropical and sub-tropical world and, as such, has also become a frequent cause of travel-associated febrile illness. In this review, we discuss our current understanding of the biological and sociological underpinnings of its emergence and its future global outlook. PMID:26918158

  19. Zika virus infections imported from Brazil to Portugal, 2015

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    L. Zé-Zé; M.B. Prata; Teixeira, T; Marques, N.; Mondragão, A.; Fernandes, R; Saraiva da Cunha, J.; Alves, M. J.

    2016-01-01

    Zika virus is an emerging arbovirus transmitted by Aedes sp. mosquitoes like the Dengue and Chikungunya viruses. Zika virus was until recently considered a mild pathogenic mosquito-borne flavivirus with very few reported benign human infections. In 2007, an epidemic in Micronesia initiated the turnover in the epidemiological history of Zika virus and more recently, the potential association with congenital microcephaly cases in Brazil 2015, still under investigation, led the World Health Orga...

  20. Neutralizing Monoclonal Antibodies Block Chikungunya Virus Entry and Release by Targeting an Epitope Critical to Viral Pathogenesis.

    Science.gov (United States)

    Jin, Jing; Liss, Nathan M; Chen, Dong-Hua; Liao, Maofu; Fox, Julie M; Shimak, Raeann M; Fong, Rachel H; Chafets, Daniel; Bakkour, Sonia; Keating, Sheila; Fomin, Marina E; Muench, Marcus O; Sherman, Michael B; Doranz, Benjamin J; Diamond, Michael S; Simmons, Graham

    2015-12-22

    We evaluated the mechanism by which neutralizing human monoclonal antibodies inhibit chikungunya virus (CHIKV) infection. Potently neutralizing antibodies (NAbs) blocked infection at multiple steps of the virus life cycle, including entry and release. Cryo-electron microscopy structures of Fab fragments of two human NAbs and chikungunya virus-like particles showed a binding footprint that spanned independent domains on neighboring E2 subunits within one viral spike, suggesting a mechanism for inhibiting low-pH-dependent membrane fusion. Detailed epitope mapping identified amino acid E2-W64 as a critical interaction residue. An escape mutation (E2-W64G) at this residue rendered CHIKV attenuated in mice. Consistent with these data, CHIKV-E2-W64G failed to emerge in vivo under the selection pressure of one of the NAbs, IM-CKV063. As our study suggests that antibodies engaging the residue E2-W64 can potently inhibit CHIKV at multiple stages of infection, antibody-based therapies or immunogens that target this region might have protective value.

  1. Sphingosine kinase 2 is a chikungunya virus host factor co-localized with the viral replication complex.

    Science.gov (United States)

    Reid, St Patrick; Tritsch, Sarah R; Kota, Krishna; Chiang, Chih-Yuan; Dong, Lian; Kenny, Tara; Brueggemann, Ernest E; Ward, Michael D; Cazares, Lisa H; Bavari, Sina

    2015-10-01

    Chikungunya virus (CHIKV) is a re-emerging alphavirus which causes severe and prolonged arthralgic febrile illness. The recent global spread of the virus and lack of approved therapeutic options makes it imperative to gain greater insight into the molecular mechanisms underlying CHIKV pathogenesis, in particular host factors recruited by the virus. In the current study, we identify sphingosine kinase 2 (SK2) as a CHIKV host factor co-localized with the viral replication complex (VRC) during infection. SK2 was demonstrated to co-localize with viral RNA and nonstructural proteins. Targeted impairment of SK2 expression or function significantly inhibited CHIKV infection. Furthermore, affinity purification-mass spectrometry studies revealed that SK2 associates with a number of proteins involved in cellular gene expression specifically during viral infection, suggesting a role in replication. Collectively these results identify SK2 as a novel CHIKV host factor.

  2. Whole-Genome Sequencing Analysis from the Chikungunya Virus Caribbean Outbreak Reveals Novel Evolutionary Genomic Elements.

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    Kenneth A Stapleford

    2016-01-01

    Full Text Available Chikungunya virus (CHIKV, an alphavirus and member of the Togaviridae family, is capable of causing severe febrile disease in humans. In December of 2013 the Asian Lineage of CHIKV spread from the Old World to the Americas, spreading rapidly throughout the New World. Given this new emergence in naïve populations we studied the viral genetic diversity present in infected individuals to understand how CHIKV may have evolved during this continuing outbreak.We used deep-sequencing technologies coupled with well-established bioinformatics pipelines to characterize the minority variants and diversity present in CHIKV infected individuals from Guadeloupe and Martinique, two islands in the center of the epidemic. We observed changes in the consensus sequence as well as a diverse range of minority variants present at various levels in the population. Furthermore, we found that overall diversity was dramatically reduced after single passages in cell lines. Finally, we constructed an infectious clone from this outbreak and identified a novel 3' untranslated region (UTR structure, not previously found in nature, that led to increased replication in insect cells.Here we preformed an intrahost quasispecies analysis of the new CHIKV outbreak in the Caribbean. We identified novel variants present in infected individuals, as well as a new 3'UTR structure, suggesting that CHIKV has rapidly evolved in a short period of time once it entered this naïve population. These studies highlight the need to continue viral diversity surveillance over time as this epidemic evolves in order to understand the evolutionary potential of CHIKV.

  3. Recombinant modified vaccinia virus Ankara expressing glycoprotein E2 of Chikungunya virus protects AG129 mice against lethal challenge.

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    Petra van den Doel

    2014-09-01

    Full Text Available Chikungunya virus (CHIKV infection is characterized by rash, acute high fever, chills, headache, nausea, photophobia, vomiting, and severe polyarthralgia. There is evidence that arthralgia can persist for years and result in long-term discomfort. Neurologic disease with fatal outcome has been documented, although at low incidences. The CHIKV RNA genome encodes five structural proteins (C, E1, E2, E3 and 6K. The E1 spike protein drives the fusion process within the cytoplasm, while the E2 protein is believed to interact with cellular receptors and therefore most probably constitutes the target of neutralizing antibodies. We have constructed recombinant Modified Vaccinia Ankara (MVA expressing E3E2, 6KE1, or the entire CHIKV envelope polyprotein cassette E3E26KE1. MVA is an appropriate platform because of its demonstrated clinical safety and its suitability for expression of various heterologous proteins. After completing the immunization scheme, animals were challenged with CHIV-S27. Immunization of AG129 mice with MVAs expressing E2 or E3E26KE1 elicited neutralizing antibodies in all animals and provided 100% protection against lethal disease. In contrast, 75% of the animals immunized with 6KE1 were protected against lethal infection. In conclusion, MVA expressing the glycoprotein E2 of CHIKV represents as an immunogenic and effective candidate vaccine against CHIKV infections.

  4. Reduced Incidence of Chikungunya Virus Infection in Communities with Ongoing Aedes Aegypti Mosquito Trap Intervention Studies - Salinas and Guayama, Puerto Rico, November 2015-February 2016.

    Science.gov (United States)

    Lorenzi, Olga D; Major, Chelsea; Acevedo, Veronica; Perez-Padilla, Janice; Rivera, Aidsa; Biggerstaff, Brad J; Munoz-Jordan, Jorge; Waterman, Stephen; Barrera, Roberto; Sharp, Tyler M

    2016-01-01

    Aedes species mosquitoes transmit chikungunya virus, as well as dengue and Zika viruses, and bite most often during the day.* Infectious mosquito bites frequently occur in and around homes (1,2). Caribbean countries first reported local transmission of chikungunya virus in December 2013, and soon after, chikungunya virus spread throughout the Americas (3). Puerto Rico reported its first laboratory-positive chikungunya case in May 2014 (4), and subsequently identified approximately 29,000 suspected cases throughout the island by the end of 2015.(†) Because conventional vector control approaches often fail to result in effective and sustainable prevention of infection with viruses transmitted by Aedes mosquitoes (5), and to improve surveillance of mosquito population densities, CDC developed an Autocidal Gravid Ovitrap (AGO) (6) to attract and capture the female Aedes aegypti mosquitoes responsible for transmission of infectious agents to humans (Figure). The AGO trap is a simple, low-cost device that requires no use of pesticides and no servicing for an extended period of time (6). PMID:27171600

  5. Chikungunya and dengue virus infections during pregnancy: seroprevalence, seroincidence and maternal-fetal transmission, southern Thailand, 2009-2010.

    Science.gov (United States)

    Laoprasopwattana, K; Suntharasaj, T; Petmanee, P; Suddeaugrai, O; Geater, A

    2016-01-01

    Limited information is available on the seroprevalence of chikungunya virus (CHIKV) infection and maternal-fetal transmission incidence of CHIKV and dengue virus (DENV) infections during the 2008-2009 CHIKV outbreak in southern Thailand. A community-based post-epidemic seroprevalence study was conducted in parturient women admitted to the Thepa District Hospital in Songkhla Province, Thailand, for delivery from November 2009 to May 2010. The women were tested for chikungunya (CHIK) IgM/IgG and dengue (DEN) IgM/IgG. Cord blood samples were also tested for CHIK IgM or DEN IgM in women who tested positive for CHIK IgM or DEN IgM, respectively. The seroprevalence of CHIKV infection (CHIK IgM or IgG positive) was 227/319 (71·2%) with pre-outbreak seroprevalence (IgM-/IgG+) of 43·6% and the seroprevalence of DENV infection was 288/319 (90·3%). Complications during pregnancy, newborn outcomes and congenital anomalies were not different in those who had recent, remote or no CHIKV infections. None of the newborns whose mothers were CHIK or DEN IgM positive had cord blood positive for both CHIK and DEN IgM. In conclusion, both CHIKV and DENV are endemic in southern Thailand; during the recent CHIKV outbreak CHIK seroprevalence increased from 43·6% to 71·2%.

  6. Comparative full genome analysis revealed E1: A226V shift in 2007 Indian Chikungunya virus isolates.

    Science.gov (United States)

    Santhosh, S R; Dash, P K; Parida, M M; Khan, M; Tiwari, M; Lakshmana Rao, P V

    2008-07-01

    The resurgence of Chikungunya virus (CHIKV) in the form of unprecedented explosive epidemic after a gap of 32 years in India is a point of major public health concern. In 2007 again there was outbreak in Kerala, India, affecting more than 25,000 cases with many reported mortalities. To understand the molecular basis of this high virulence and its implication in large-scale epidemic, a detailed systematic serological, virological and molecular investigation was undertaken with the epidemic samples of Kerala-2007. The comparative analysis of full genome sequence of Chikungunya virus isolate of 2007 with 2006 revealed three unique substitutions in structural and non-structural genes of 2007 isolate [two in E1 region (V14A and A226V) and one in Nsp1 (M184T)]. Our finding further substantiates the association of A226V shift in E1 gene with evolutionary success possibly due to adaptation in the mosquito vector with progression of epidemic, as observed in Reunion Island. This A226V shift which was absent in all 2006 Indian isolates, is found to be present in the four 2007 isolates, analysed in this study. These unique molecular features of the 2007 isolates with the progression of the epidemic from 2005 to 2007 demonstrate their high evolutionary and epidemic potential and thereby suggesting possible implication in higher magnitude and virulence of this outbreak. PMID:18384900

  7. Chikungunya virus-like particles are more immunogenic in a lethal AG129 mouse model compared to glycoprotein El or E2 subunits

    NARCIS (Netherlands)

    Metz, S.W.H.; Martina, B.E.; Doel, van den P.; Geertsema, C.; Osterhaus, A.D.; Vlak, J.M.; Pijlman, G.P.

    2013-01-01

    Chikungunya virus (CHIKV) causes acute illness characterized by fever and long-lasting arthritic symptoms. The need for a safe and effective vaccine against CHM/infections is on the rise due to on-going vector spread and increasing severity of clinical complications. Here we report the results of a

  8. The C-terminal domain of chikungunya virus nsP2 independently governs viral RNA replication, cytopathicity, and inhibition of interferon signaling

    NARCIS (Netherlands)

    Fros, J.J.; Maten, van der E.; Vlak, J.M.; Pijlman, G.P.

    2013-01-01

    Alphavirus nonstructural protein 2 (nsP2) has pivotal roles in viral RNA replication, host cell shutoff, and inhibition of antiviral responses. Mutations that individually rendered other alphaviruses noncytopathic were introduced into chikungunya virus nsP2. Results show that (i) nsP2 mutation P718S

  9. Poly (I:C, an agonist of toll-like receptor-3, inhibits replication of the Chikungunya virus in BEAS-2B cells

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    Li Yong-Gang

    2012-06-01

    Full Text Available Abstract Background Double-stranded RNA (dsRNA and its mimic, polyinosinic acid: polycytidylic acid [Poly (I:C], are recognized by toll-like receptor 3 (TLR3 and induce interferon (IFN-β in many cell types. Poly (I:C is the most potent IFN inducer. In in vivo mouse studies, intraperitoneal injection of Poly (I:C elicited IFN-α/β production and natural killer (NK cells activation. The TLR3 pathway is suggested to contribute to innate immune responses against many viruses, including influenza virus, respiratory syncytial virus, herpes simplex virus 2, and murine cytomegalovirus. In Chikungunya virus (CHIKV infection, the viruses are cleared within 7–10 days postinfection before adaptive immune responses emerge. The innate immune response is important for CHIKV clearance. Results The effects of Poly (I:C on the replication of CHIKV in human bronchial epithelial cells, BEAS-2B, were studied. Poly (I:C suppressed cytopathic effects (CPE induced by CHIKV infection in BEAS-2B cells in the presence of Poly (I:C and inhibited the replication of CHIKV in the cells. The virus titers of Poly (I:C-treated cells were much lower compared with those of untreated cells. CHIKV infection and Poly (I:C treatment of BEAS-2B cells induced the production of IFN-β and increased the expression of anti-viral genes, including IFN-α, IFN-β, MxA, and OAS. Both Poly (I:C and CHIKV infection upregulate the expression of TLR3 in BEAS-2B cells. Conclusions CHIKV is sensitive to innate immune response induced by Poly (I:C. The inhibition of CHIKV replication by Poly (I:C may be through the induction of TLR3, which triggers the production of IFNs and other anti-viral genes. The innate immune response is important to clear CHIKV in infected cells.

  10. 基孔肯雅病毒实验室检测方法研究进展%Research progress of the detecting methods for chikungunya virus

    Institute of Scientific and Technical Information of China (English)

    李小波; 丁国允; 黄吉城; 郑夔

    2012-01-01

    基孔肯雅热是由基孔肯雅病毒引起的一种急性虫媒传染病,基孔肯雅病毒属甲病毒属,披膜病毒科.近年来,该病毒曾引起全球多处疫情暴发,并造成全球性的公共卫生问题.本文对基孔肯雅病毒及其实验室检测方法作一综述,以指导国内开展对该病的检测.%Chikungunya virus is an emerging alpha-virus belonging to family Togaviridae. It has caused widespread epidemics during the past several years, which brought about a series of public health problems and became a global concern. This is an introduction to Chikungunya virus and provides all-around detecting methods for the virus.

  11. An imported case of Chikungunya fever from Madagascar: use of the sentinel traveller for detecting emerging arboviral infections in tropical and European countries.

    Science.gov (United States)

    Pistone, Thierry; Ezzedine, Khaled; Schuffenecker, Isabelle; Receveur, Marie-Catherine; Malvy, Denis

    2009-01-01

    A major Chikungunya virus (CHIKV) epidemic affected the South-Western Indian Ocean islands in 2005. This major outbreak raised concerns about the possibility of the emergence of CHIKV infections in Europe as an autochthonous CHIKV outbreak occurred in the Ravenna region of Italy during the summer of 2007 and was linked to a viraemic index case originating in Kerala, India. This report highlights the need for surveillance in countries where such emerging infections could be introduced by returning travellers. PMID:19174303

  12. Diagnostic potential of monoclonal antibodies against the capsid protein of chikungunya virus for detection of recent infection.

    Science.gov (United States)

    Damle, R G; Jayaram, N; Kulkarni, S M; Nigade, K; Khutwad, K; Gosavi, S; Parashar, D

    2016-06-01

    Chikungunya fever is self-limiting. However, neurological and hemorrhagic complications have been seen in recent outbreaks. The clinical manifestations of this disease are similar to those of dengue virus infection, indicating the need for differential diagnosis in areas such as India, which are endemic for both viruses. The aim of the present study was to develop monoclonal antibodies (MAbs) against Chikungunya virus (CHIKV) and assess their use in MAb-based IgM capture ELISA (MAC ELISA). The ELISA detects CHIKV-specific IgM antibodies, a marker of recent infection, in a patient's serum. One IgG1 and two IgM isotype hybrids were obtained. All of the subclones derived from the IgG1 hybrid recognized the C protein of CHIKV. The anti-C MAb ClVE4/D9 was the most promising as a detector antibody in MAC ELISA (C-MAb ELISA) yielding higher positive-to-negative (P/N) ratios. When compared with the CHIKV MAC ELISA kit developed by the National Institute of Virology (NIV), Pune (NIV MAC ELISA), the sensitivity of the test was 87.01 % with 100 % specificity. The positive and negative predictive values (PPV and NPV) were 100 % and 94.47 %, respectively. In precision testing, standard deviation (SD) and coefficient of variation (% CV) values of the C-MAb ELISA were within acceptable limits. The C-MAb ELISA detected anti-CHIKV IgM in serum of patients up to five months after the onset of infection, indicating that anti-C MAbs have strong potential for use in MAC ELISA to detect recent CHIKV infection. PMID:27016930

  13. Development and evaluation of a one-step SYBR-Green I-based real-time RT-PCR assay for the detection and quantification of Chikungunya virus in human, monkey and mosquito samples.

    Science.gov (United States)

    Ummul Haninah, A; Vasan, S S; Ravindran, T; Chandru, A; Lee, H L; Shamala Devi, S

    2010-12-01

    This paper reports the development of a one-step SYBR-Green I-based realtime RT-PCR assay for the detection and quantification of Chikungunya virus (CHIKV) in human, monkey and mosquito samples by targeting the E1 structural gene. A preliminary evaluation of this assay has been successfully completed using 71 samples, consisting of a panel of negative control sera, sera from healthy individuals, sera from patients with acute disease from which CHIKV had been isolated, as well as monkey sera and adult mosquito samples obtained during the chikungunya fever outbreak in Malaysia in 2008. The assay was found to be 100-fold more sensitive than the conventional RT-PCR with a detection limit of 4.12x10(0) RNA copies/μl. The specificity of the assay was tested against other related viruses such as Dengue (serotypes 1-4), Japanese encephalitis, Herpes Simplex, Parainfluenza, Sindbis, Ross River, Yellow fever and West Nile viruses. The sensitivity, specificity and efficiency of this assay were 100%, 100% and 96.8% respectively. This study on early diagnostics is of importance to all endemic countries, especially Malaysia, which has been facing increasingly frequent and bigger outbreaks due to this virus since 1999. PMID:21399603

  14. A small antigenic determinant of the Chikungunya virus E2 protein is sufficient to induce neutralizing antibodies which are partially protective in mice.

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    Christopher Weber

    2015-04-01

    Full Text Available The mosquito-borne Chikungunya virus (CHIKV causes high fever and severe joint pain in humans. It is expected to spread in the future to Europe and has recently reached the USA due to globalization, climate change and vector switch. Despite this, little is known about the virus life cycle and, so far, there is no specific treatment or vaccination against Chikungunya infections. We aimed here to identify small antigenic determinants of the CHIKV E2 protein able to induce neutralizing immune responses.E2 enables attachment of the virus to target cells and a humoral immune response against E2 should protect from CHIKV infections. Seven recombinant proteins derived from E2 and consisting of linear and/or structural antigens were created, and were expressed in and purified from E. coli. BALB/c mice were vaccinated with these recombinant proteins and the mouse sera were screened for neutralizing antibodies. Whereas a linear N-terminally exposed peptide (L and surface-exposed parts of the E2 domain A (sA alone did not induce neutralizing antibodies, a construct containing domain B and a part of the β-ribbon (called B+ was sufficient to induce neutralizing antibodies. Furthermore, domain sA fused to B+ (sAB+ induced the highest amount of neutralizing antibodies. Therefore, the construct sAB+ was used to generate a recombinant modified vaccinia virus Ankara (MVA, MVA-CHIKV-sAB+. Mice were vaccinated with MVA-CHIKV-sAB+ and/or the recombinant protein sAB+ and were subsequently challenged with wild-type CHIKV. Whereas four vaccinations with MVA-CHIKV-sAB+ were not sufficient to protect mice from a CHIKV infection, protein vaccination with sAB+ markedly reduced the viral titers of vaccinated mice.The recombinant protein sAB+ contains important structural antigens for a neutralizing antibody response in mice and its formulation with appropriate adjuvants might lead to a future CHIKV vaccine.

  15. Clinical and histopathological features of fatal cases with dengue and chikungunya virus co-infection in Colombia, 2014 to 2015.

    Science.gov (United States)

    Mercado, Marcela; Acosta-Reyes, Jorge; Parra, Edgar; Pardo, Lissethe; Rico, Angélica; Campo, Alfonso; Navarro, Edgar; Viasus, Diego

    2016-06-01

    We report clinical features and histopathological findings in fatal cases with dengue (DENV) and chikungunya (CHIKV) co-infection identified at the Colombian National Institute of Health between September 2014 and October 2015. Seven such cases were documented. Dengue serotype 2 virus was identified in six cases. All patients were adults and comorbidities were present in four. Fever, arthralgia or myalgia was present in all cases. The frequency of rash, haemorrhage, oedema, and gastrointestinal symptoms was variable. Laboratory findings such as thrombocytopenia, renal failure, and leukocyte count were also inconsistent between cases. Post-mortem tissue examination documented focal hepatocellular coagulative necrosis in three cases, incipient acute pericarditis in one and tubulointerstitial nephritis in one. This study provides evidence of mortality in patients with DENV and CHIKV co-infection. Fatal cases were characterised by variable clinical and laboratory features. Evaluation of histopathology of autopsy tissues provided evidence of the pathological consequences of the disease.

  16. Clinical and histopathological features of fatal cases with dengue and chikungunya virus co-infection in Colombia, 2014 to 2015.

    Science.gov (United States)

    Mercado, Marcela; Acosta-Reyes, Jorge; Parra, Edgar; Pardo, Lissethe; Rico, Angélica; Campo, Alfonso; Navarro, Edgar; Viasus, Diego

    2016-06-01

    We report clinical features and histopathological findings in fatal cases with dengue (DENV) and chikungunya (CHIKV) co-infection identified at the Colombian National Institute of Health between September 2014 and October 2015. Seven such cases were documented. Dengue serotype 2 virus was identified in six cases. All patients were adults and comorbidities were present in four. Fever, arthralgia or myalgia was present in all cases. The frequency of rash, haemorrhage, oedema, and gastrointestinal symptoms was variable. Laboratory findings such as thrombocytopenia, renal failure, and leukocyte count were also inconsistent between cases. Post-mortem tissue examination documented focal hepatocellular coagulative necrosis in three cases, incipient acute pericarditis in one and tubulointerstitial nephritis in one. This study provides evidence of mortality in patients with DENV and CHIKV co-infection. Fatal cases were characterised by variable clinical and laboratory features. Evaluation of histopathology of autopsy tissues provided evidence of the pathological consequences of the disease. PMID:27277216

  17. Chikungunya virus exploits miR-146a to regulate NF-κB pathway in human synovial fibroblasts.

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    Sakthi Priya Selvamani

    Full Text Available OBJECTIVES: Chikungunya virus causes chronic infection with manifestations of joint pain. Human synovial fibroblasts get infected with CHIKV and could lead to pro-inflammatory responses. MicroRNAs have potentials to regulate the gene expression of various anti-viral and pro-inflammatory genes. The study aims to investigate the role of miR-146a in modulation of inflammatory responses of human synovial fibroblasts by Chikungunya virus. METHODS: To study the role of miR-146a in CHIKV pathogenesis in human synovial cells and underlying inflammatory manifestations, we performed CHIKV infection in primary human synovial fibroblasts. Western blotting, real-time PCR, luciferase reporter assay, overexpression and knockdown of cellular miR-146a strategies have been employed to validate the role of miR-146a in regulation of pro-inflammatory NF-κB pathway. RESULTS: CHIKV infection induced the expression of cellular miR-146a, which resulted into down-regulation of TRAF6, IRAK1, IRAK2 and increased replication of CHIKV in human synovial fibroblasts. Exogenous expression of miR-146a in human synovial fibroblasts led to decreased expression of TRAF6, IRAK1, IRAK2 and decreased replication of CHIKV. Inhibition of cellular miR-146a by anti-miR-146a restored the expression levels of TRAF6, IRAK1 and IRAK2. Downregulation of TRAF6, IRAK1 and IRAK2 led to downstream decreased NF-κB activation through negative feedback loop. CONCLUSION: This study demonstrated the mechanism of exploitation of cellular miR-146a by CHIKV in modulating the host antiviral immune response in primary human synovial fibroblasts.

  18. Induction of GADD34 is necessary for dsRNA-dependent interferon-β production and participates in the control of Chikungunya virus infection.

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    Giovanna Clavarino

    Full Text Available Nucleic acid sensing by cells is a key feature of antiviral responses, which generally result in type-I Interferon production and tissue protection. However, detection of double-stranded RNAs in virus-infected cells promotes two concomitant and apparently conflicting events. The dsRNA-dependent protein kinase (PKR phosphorylates translation initiation factor 2-alpha (eIF2α and inhibits protein synthesis, whereas cytosolic DExD/H box RNA helicases induce expression of type I-IFN and other cytokines. We demonstrate that the phosphatase-1 cofactor, growth arrest and DNA damage-inducible protein 34 (GADD34/Ppp1r15a, an important component of the unfolded protein response (UPR, is absolutely required for type I-IFN and IL-6 production by mouse embryonic fibroblasts (MEFs in response to dsRNA. GADD34 expression in MEFs is dependent on PKR activation, linking cytosolic microbial sensing with the ATF4 branch of the UPR. The importance of this link for anti-viral immunity is underlined by the extreme susceptibility of GADD34-deficient fibroblasts and neonate mice to Chikungunya virus infection.

  19. Expression of plasmid-based shRNA against the E1 and nsP1 genes effectively silenced Chikungunya virus replication.

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    Shirley Lam

    Full Text Available BACKGROUND: Chikungunya virus (CHIKV is a re-emerging alphavirus that causes chikungunya fever and persistent arthralgia in humans. Currently, there is no effective vaccine or antiviral against CHIKV infection. Therefore, this study evaluates whether RNA interference which targets at viral genomic level may be a novel antiviral strategy to inhibit the medically important CHIKV infection. METHODS: Plasmid-based small hairpin RNA (shRNA was investigated for its efficacy in inhibiting CHIKV replication. Three shRNAs designed against CHIKV Capsid, E1 and nsP1 genes were transfected to establish stable shRNA-expressing cell clones. Following infection of stable shRNA cells clones with CHIKV at M.O.I. 1, viral plaque assay, Western blotting and transmission electron microscopy were performed. The in vivo efficacy of shRNA against CHIKV replication was also evaluated in a suckling murine model of CHIKV infection. RESULTS: Cell clones expressing shRNAs against CHIKV E1 and nsP1 genes displayed significant inhibition of infectious CHIKV production, while shRNA Capsid demonstrated a modest inhibitory effect as compared to scrambled shRNA cell clones and non-transfected cell controls. Western blot analysis of CHIKV E2 protein expression and transmission electron microscopy of shRNA E1 and nsP1 cell clones collectively demonstrated similar inhibitory trends against CHIKV replication. shRNA E1 showed non cell-type specific anti-CHIKV effects and broad-spectrum silencing against different geographical strains of CHIKV. Furthermore, shRNA E1 clones did not exert any inhibition against Dengue virus and Sindbis virus replication, thus indicating the high specificity of shRNA against CHIKV replication. Moreover, no shRNA-resistant CHIKV mutant was generated after 50 passages of CHIKV in the stable cell clones. More importantly, strong and sustained anti-CHIKV protection was conferred in suckling mice pre-treated with shRNA E1. CONCLUSION: Taken together, these

  20. Effect of Holding Conditions on the Detection of Chikungunya and Venezuelan Equine Encephalitis Viruses in Mosquito Pools.

    Science.gov (United States)

    Andrews, Elizabeth S; Turell, Michael J

    2016-03-01

    Emerging and re-emerging arboviruses continue to be a threat to global public health, and viral surveillance of mosquito populations is critical for mosquito control operations. Due to the tropical climate of many of the affected areas, it may be difficult to maintain a cold chain as the samples travel from collection sites to laboratories for testing. We determined how suboptimal holding temperatures affected the ability to detect viruses in pools of mosquitoes. Adult female Aedes albopictus and Ae. taeniorhynchus individuals were inoculated with chikungunya virus or Venezuelan equine encephalitis virus suspensions, respectively, and placed at 26°C for 8 days. One infected mosquito was then added to a vial of 24 negative mosquitoes and held at -80°C, -20°C, 4°C, 22°C, or 35°C for up to 14 days. Mosquito pools were analyzed for both infectious virus by plaque assay and for viral ribonucleic acid (RNA) with reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR). At higher temperatures, the amount of infectious virus decreased rapidly, but viruses in samples held at 4°C or lower remained relatively stable. In contrast, viral RNA was detectable from pools held at all temperatures and holding times by RT-qPCR. Cycle threshold (Ct) values increased as temperatures and holding times increased. These findings suggest that if viral RNA detection is the goal of surveillance efforts, then mosquito pools do not require storage at ≤4°C. This enhances the feasibility of field-based arbovirus surveillance programs in which maintaining a cold chain may not be a possibility. PMID:27105216

  1. Estimating drivers of autochthonous transmission of chikungunya virus in its invasion of the americas.

    Science.gov (United States)

    Perkins, T Alex; Metcalf, C Jessica E; Grenfell, Bryan T; Tatem, Andrew J

    2015-01-01

    Background Chikungunya is an emerging arbovirus that has caused explosive outbreaks in Africa and Asia for decades and invaded the Americas just over a year ago. During this ongoing invasion, it has spread to 45 countries where it has been transmitted autochthonously, infecting nearly 1.3 million people in total. Methods Here, we made use of weekly, country-level case reports to infer relationships between transmission and two putative climatic drivers: temperature and precipitation averaged across each country on a monthly basis. To do so, we used a TSIR model that enabled us to infer a parametric relationship between climatic drivers and transmission potential, and we applied a new method for incorporating a probabilistic description of the serial interval distribution into the TSIR framework. Results We found significant relationships between transmission and linear and quadratic terms for temperature and precipitation and a linear term for log incidence during the previous pathogen generation. The lattermost suggests that case numbers three to four weeks ago are largely predictive of current case numbers. This effect is quite nonlinear at the country level, however, due to an estimated mixing parameter of 0.74. Relationships between transmission and the climatic variables that we estimated were biologically plausible and in line with expectations. Conclusions Our analysis suggests that autochthonous transmission of Chikungunya in the Americas can be correlated successfully with putative climatic drivers, even at the coarse scale of countries and using long-term average climate data. Overall, this provides a preliminary suggestion that successfully forecasting the future trajectory of a Chikungunya outbreak and the receptivity of virgin areas may be possible. Our results also provide tentative estimates of timeframes and areas of greatest risk, and our extension of the TSIR model provides a novel tool for modeling vector-borne disease transmission. PMID:25737803

  2. Investigation Into an Outbreak of Dengue-like Illness in Pernambuco, Brazil, Revealed a Cocirculation of Zika, Chikungunya, and Dengue Virus Type 1.

    Science.gov (United States)

    Pessôa, Rodrigo; Patriota, João Veras; Lourdes de Souza, Maria de; Felix, Alvina Clara; Mamede, Nubia; Sanabani, Sabri S

    2016-03-01

    In April 2015, an outbreak of dengue-like illness occurred in Tuparetama, a small city in the northeast region of Brazil; this outbreak was characterized by its fast expansion. An investigation was initiated to identify the viral etiologies and advise the health authorities on implementing control measures to contain the outbreak. This is the first report of this outbreak in the northeast, even though a few cases were documented earlier in a neighboring city.Plasma samples were obtained from 77 suspected dengue patients attending the main hospital in the city. Laboratory assays, such as real-time reverse transcription polymerase chain reaction, virus cDNA sequencing, and enzyme-linked immunosorbent assay, were employed to identify the infecting virus and molecular phylogenetic analysis was performed to define the circulating viral genotypes.RNA of Zika virus (ZIKV) and Dengue virus (DENV) or IgM antibodies (Abs) to DENV or chikungunya (CHIKV) were detected in 40 of the 77 plasma samples (51.9%). DENV was found in 9 patients (11.7%), ZIKV was found in 31 patients (40.2%), CHIKV in 1 patient (1.3%), and coinfection of DENV and ZIKV was detected in 2 patients (2.6%). The phylogenetic analysis of 2 available partial DENV and 14 ZIKV sequences revealed the identities of genotype 1 and the Asiatic lineage, respectively.Consistent with recent reports from the same region, our results showed that the ongoing outbreak is caused by ZIKV, DENV, and CHIKV. This emphasizes the need for a routine and differential diagnosis of arboviruses in patients with dengue-like illness. Coordinated efforts are necessary to contain the outbreak. Continued surveillance will be important to assess the effectiveness of current and future prevention strategies. PMID:27015222

  3. Investigation Into an Outbreak of Dengue-like Illness in Pernambuco, Brazil, Revealed a Cocirculation of Zika, Chikungunya, and Dengue Virus Type 1.

    Science.gov (United States)

    Pessôa, Rodrigo; Patriota, João Veras; Lourdes de Souza, Maria de; Felix, Alvina Clara; Mamede, Nubia; Sanabani, Sabri S

    2016-03-01

    In April 2015, an outbreak of dengue-like illness occurred in Tuparetama, a small city in the northeast region of Brazil; this outbreak was characterized by its fast expansion. An investigation was initiated to identify the viral etiologies and advise the health authorities on implementing control measures to contain the outbreak. This is the first report of this outbreak in the northeast, even though a few cases were documented earlier in a neighboring city.Plasma samples were obtained from 77 suspected dengue patients attending the main hospital in the city. Laboratory assays, such as real-time reverse transcription polymerase chain reaction, virus cDNA sequencing, and enzyme-linked immunosorbent assay, were employed to identify the infecting virus and molecular phylogenetic analysis was performed to define the circulating viral genotypes.RNA of Zika virus (ZIKV) and Dengue virus (DENV) or IgM antibodies (Abs) to DENV or chikungunya (CHIKV) were detected in 40 of the 77 plasma samples (51.9%). DENV was found in 9 patients (11.7%), ZIKV was found in 31 patients (40.2%), CHIKV in 1 patient (1.3%), and coinfection of DENV and ZIKV was detected in 2 patients (2.6%). The phylogenetic analysis of 2 available partial DENV and 14 ZIKV sequences revealed the identities of genotype 1 and the Asiatic lineage, respectively.Consistent with recent reports from the same region, our results showed that the ongoing outbreak is caused by ZIKV, DENV, and CHIKV. This emphasizes the need for a routine and differential diagnosis of arboviruses in patients with dengue-like illness. Coordinated efforts are necessary to contain the outbreak. Continued surveillance will be important to assess the effectiveness of current and future prevention strategies.

  4. Identification and genetic characterization of chikungunya virus from Aedes mosquito vector collected in the Lucknow district, North India.

    Science.gov (United States)

    Nyari, N; Maan, H S; Sharma, S; Pandey, S N; Dhole, T N

    2016-06-01

    Chikungunya fever is an emerging mosquito-borne disease caused by the infection with chikungunya virus (CHIKV). The CHIKV has been rarely detected in mosquito vectors from Northern India, since vector surveillance is an effective strategy in controlling and preventing CHIKV transmission. Thus, virological investigation for CHIKV among mosquitoes of Aedes (A.) species was carried out in the Lucknow district during March 2010 to October 2011. We collected adult mosquitoes from areas with CHIKV positive patients. The adult Aedes mosquito samples were pooled, homogenized, clarified and tested for CHIKV by nonstructural protein 1 (nsP1) gene based polymerase chain reaction (PCR). A total 91 mosquito pools comprising of adult A. aegypti and A. albopictus were tested for CHIKV. The partial envelope protein (E1) gene sequences of mosquito-borne CHIKV strains were analyzed for genotyping. Of 91 pools, 6 pools of A. aegypti; and 2 pools of A. albopictus mosquitoes were identified positive for CHIKV by PCR. The phylogenetic analysis revealed clustering of CHIKV strains in two sub-lineages within the monophyletic East-Central South African (ECSA) genotype. Novel amino acid changes at the positions 294 (P294L) and 295 (S295F) were observed during analysis of amino acid sequence of the partial E1 gene. This study demonstrates the genetic diversity of circulating CHIKV strains and reports the first detection of CHIKV strains in Aedes vector species from the state of Uttar Pradesh. These findings have implication for vector control strategies to mitigate vector population to prevent the likelihood of CHIKV epidemic in the near future. PMID:26943997

  5. Inhibitors of alphavirus entry and replication identified with a stable Chikungunya replicon cell line and virus-based assays.

    Directory of Open Access Journals (Sweden)

    Leena Pohjala

    Full Text Available Chikungunya virus (CHIKV, an alphavirus, has recently caused epidemic outbreaks and is therefore considered a re-emerging pathogen for which no effective treatment is available. In this study, a CHIKV replicon containing the virus replicase proteins together with puromycin acetyltransferase, EGFP and Renilla luciferase marker genes was constructed. The replicon was transfected into BHK cells to yield a stable cell line. A non-cytopathic phenotype was achieved by a Pro718 to Gly substitution and a five amino acid insertion within non-structural protein 2 (nsP2, obtained through selection for stable growth. Characterization of the replicon cell line by Northern blotting analysis revealed reduced levels of viral RNA synthesis. The CHIKV replicon cell line was validated for antiviral screening in 96-well format and used for a focused screen of 356 compounds (natural compounds and clinically approved drugs. The 5,7-dihydroxyflavones apigenin, chrysin, naringenin and silybin were found to suppress activities of EGFP and Rluc marker genes expressed by the CHIKV replicon. In a concomitant screen against Semliki Forest virus (SFV, their anti-alphaviral activity was confirmed and several additional inhibitors of SFV with IC₅₀ values between 0.4 and 24 µM were identified. Chlorpromazine and five other compounds with a 10H-phenothiazinyl structure were shown to inhibit SFV entry using a novel entry assay based on a temperature-sensitive SFV mutant. These compounds also reduced SFV and Sindbis virus-induced cytopathic effect and inhibited SFV virion production in virus yield experiments. Finally, antiviral effects of selected compounds were confirmed using infectious CHIKV. In summary, the presented approach for discovering alphaviral inhibitors enabled us to identify potential lead structures for the development of alphavirus entry and replication phase inhibitors as well as demonstrated the usefulness of CHIKV replicon and SFV as biosafe surrogate

  6. Impact of Wolbachia on infection with chikungunya and yellow fever viruses in the mosquito vector Aedes aegypti.

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    Andrew F van den Hurk

    Full Text Available Incidence of disease due to dengue (DENV, chikungunya (CHIKV and yellow fever (YFV viruses is increasing in many parts of the world. The viruses are primarily transmitted by Aedes aegypti, a highly domesticated mosquito species that is notoriously difficult to control. When transinfected into Ae. aegypti, the intracellular bacterium Wolbachia has recently been shown to inhibit replication of DENVs, CHIKV, malaria parasites and filarial nematodes, providing a potentially powerful biocontrol strategy for human pathogens. Because the extent of pathogen reduction can be influenced by the strain of bacterium, we examined whether the wMel strain of Wolbachia influenced CHIKV and YFV infection in Ae. aegypti. Following exposure to viremic blood meals, CHIKV infection and dissemination rates were significantly reduced in mosquitoes with the wMel strain of Wolbachia compared to Wolbachia-uninfected controls. However, similar rates of infection and dissemination were observed in wMel infected and non-infected Ae. aegypti when intrathoracic inoculation was used to deliver virus. YFV infection, dissemination and replication were similar in wMel-infected and control mosquitoes following intrathoracic inoculations. In contrast, mosquitoes with the wMelPop strain of Wolbachia showed at least a 10(4 times reduction in YFV RNA copies compared to controls. The extent of reduction in virus infection depended on Wolbachia strain, titer and strain of the virus, and mode of exposure. Although originally proposed for dengue biocontrol, our results indicate a Wolbachia-based strategy also holds considerable promise for YFV and CHIKV suppression.

  7. A polarized cell model for Chikungunya virus infection: entry and egress of virus occurs at the apical domain of polarized cells.

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    Pei Jin Lim

    2014-02-01

    Full Text Available Chikungunya virus (CHIKV has resulted in several outbreaks in the past six decades. The clinical symptoms of Chikungunya infection include fever, skin rash, arthralgia, and an increasing incidence of encephalitis. The re-emergence of CHIKV with more severe pathogenesis highlights its potential threat on our human health. In this study, polarized HBMEC, polarized Vero C1008 and non-polarized Vero cells grown on cell culture inserts were infected with CHIKV apically or basolaterally. Plaque assays, viral binding assays and immunofluorescence assays demonstrated apical entry and release of CHIKV in polarized HBMEC and Vero C1008. Drug treatment studies were performed to elucidate both host cell and viral factors involved in the sorting and release of CHIKV at the apical domain of polarized cells. Disruption of host cell myosin II, microtubule and microfilament networks did not disrupt the polarized release of CHIKV. However, treatment with tunicamycin resulted in a bi-directional release of CHIKV, suggesting that N-glycans of CHIKV envelope glycoproteins could serve as apical sorting signals.

  8. The viral capping enzyme nsP1: a novel target for the inhibition of chikungunya virus infection

    Science.gov (United States)

    Delang, L.; Li, C.; Tas, A.; Quérat, G.; Albulescu, I. C.; De Burghgraeve, T.; Guerrero, N. A. Segura; Gigante, A.; Piorkowski, G.; Decroly, E.; Jochmans, D.; Canard, B.; Snijder, E. J.; Pérez-Pérez, M. J.; van Hemert, M. J.; Coutard, B.; Leyssen, P.; Neyts, J.

    2016-01-01

    The chikungunya virus (CHIKV) has become a substantial global health threat due to its massive re-emergence, the considerable disease burden and the lack of vaccines or therapeutics. We discovered a novel class of small molecules ([1,2,3]triazolo[4,5-d]pyrimidin-7(6H)-ones) with potent in vitro activity against CHIKV isolates from different geographical regions. Drug-resistant variants were selected and these carried a P34S substitution in non-structural protein 1 (nsP1), the main enzyme involved in alphavirus RNA capping. Biochemical assays using nsP1 of the related Venezuelan equine encephalitis virus revealed that the compounds specifically inhibit the guanylylation of nsP1. This is, to the best of our knowledge, the first report demonstrating that the alphavirus capping machinery is an excellent antiviral drug target. Considering the lack of options to treat CHIKV infections, this series of compounds with their unique (alphavirus-specific) target offers promise for the development of therapy for CHIKV infections. PMID:27545976

  9. A DNA vaccine against chikungunya virus is protective in mice and induces neutralizing antibodies in mice and nonhuman primates.

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    Karthik Mallilankaraman

    Full Text Available Chikungunya virus (CHIKV is an emerging mosquito-borne alphavirus indigenous to tropical Africa and Asia. Acute illness is characterized by fever, arthralgias, conjunctivitis, rash, and sometimes arthritis. Relatively little is known about the antigenic targets for immunity, and no licensed vaccines or therapeutics are currently available for the pathogen. While the Aedes aegypti mosquito is its primary vector, recent evidence suggests that other carriers can transmit CHIKV thus raising concerns about its spread outside of natural endemic areas to new countries including the U.S. and Europe. Considering the potential for pandemic spread, understanding the development of immunity is paramount to the development of effective counter measures against CHIKV. In this study, we isolated a new CHIKV virus from an acutely infected human patient and developed a defined viral challenge stock in mice that allowed us to study viral pathogenesis and develop a viral neutralization assay. We then constructed a synthetic DNA vaccine delivered by in vivo electroporation (EP that expresses a component of the CHIKV envelope glycoprotein and used this model to evaluate its efficacy. Vaccination induced robust antigen-specific cellular and humoral immune responses, which individually were capable of providing protection against CHIKV challenge in mice. Furthermore, vaccine studies in rhesus macaques demonstrated induction of nAb responses, which mimicked those induced in convalescent human patient sera. These data suggest a protective role for nAb against CHIKV disease and support further study of envelope-based CHIKV DNA vaccines.

  10. Chikungunya virus neutralization antigens and direct cell-to-cell transmission are revealed by human antibody-escape mutants.

    Directory of Open Access Journals (Sweden)

    Chia Yin Lee

    2011-12-01

    Full Text Available Chikungunya virus (CHIKV is an alphavirus responsible for numerous epidemics throughout Africa and Asia, causing infectious arthritis and reportedly linked with fatal infections in newborns and elderly. Previous studies in animal models indicate that humoral immunity can protect against CHIKV infection, but despite the potential efficacy of B-cell-driven intervention strategies, there are no virus-specific vaccines or therapies currently available. In addition, CHIKV has been reported to elicit long-lasting virus-specific IgM in humans, and to establish long-term persistence in non-human primates, suggesting that the virus might evade immune defenses to establish chronic infections in man. However, the mechanisms of immune evasion potentially employed by CHIKV remain uncharacterized. We previously described two human monoclonal antibodies that potently neutralize CHIKV infection. In the current report, we have characterized CHIKV mutants that escape antibody-dependent neutralization to identify the CHIKV E2 domain B and fusion loop "groove" as the primary determinants of CHIKV interaction with these antibodies. Furthermore, for the first time, we have also demonstrated direct CHIKV cell-to-cell transmission, as a mechanism that involves the E2 domain A and that is associated with viral resistance to antibody-dependent neutralization. Identification of CHIKV sub-domains that are associated with human protective immunity, will pave the way for the development of CHIKV-specific sub-domain vaccination strategies. Moreover, the clear demonstration of CHIKV cell-to-cell transmission and its possible role in the establishment of CHIKV persistence, will also inform the development of future anti-viral interventions. These data shed new light on CHIKV-host interactions that will help to combat human CHIKV infection and inform future studies of CHIKV pathogenesis.

  11. Chikungunya virus induces IPS-1-dependent innate immune activation and protein kinase R-independent translational shutoff.

    Science.gov (United States)

    White, Laura K; Sali, Tina; Alvarado, David; Gatti, Evelina; Pierre, Philippe; Streblow, Daniel; Defilippis, Victor R

    2011-01-01

    Chikungunya virus (CHIKV) is an arthritogenic mosquito-transmitted alphavirus that is undergoing reemergence in areas around the Indian Ocean. Despite the current and potential danger posed by this virus, we know surprisingly little about the induction and evasion of CHIKV-associated antiviral immune responses. With this in mind we investigated innate immune reactions to CHIKV in human fibroblasts, a demonstrable in vivo target of virus replication and spread. We show that CHIKV infection leads to activation of the transcription factor interferon regulatory factor 3 (IRF3) and subsequent transcription of IRF3-dependent antiviral genes, including beta interferon (IFN-β). IRF3 activation occurs by way of a virus-induced innate immune signaling pathway that includes the adaptor molecule interferon promoter stimulator 1 (IPS-1). Despite strong transcriptional upregulation of these genes, however, translation of the corresponding proteins is not observed. We further demonstrate that translation of cellular (but not viral) genes is blocked during infection and that although CHIKV is found to trigger inactivation of the translational molecule eukaryotic initiation factor subunit 2α by way of the double-stranded RNA sensor protein kinase R, this response is not required for the block to protein synthesis. Furthermore, overall diminution of cellular RNA synthesis is also observed in the presence of CHIKV and transcription of IRF3-dependent antiviral genes appears specifically blocked late in infection. We hypothesize that the observed absence of IFN-β and antiviral proteins during infection results from an evasion mechanism exhibited by CHIKV that is dependent on widespread shutoff of cellular protein synthesis and a targeted block to late synthesis of antiviral mRNA transcripts.

  12. Dengue and Chikungunya Vector Control Pocket Guide

    Science.gov (United States)

    This technical guide consolidates information and procedures for surveillance and control of mosquitoes that transmit dengue and chikungunya viruses. The guide focuses on mosquitoes that transmit dengue but also makes reference to chikungunya and yellow fever because the pathogens that cause these ...

  13. Chikungunya fever presenting with protracted severe pruritus.

    Science.gov (United States)

    Cunha, Burke A; Leonichev, Victoria B; Raza, Muhammad

    2016-01-01

    Travelers returning from the tropics often present with rash/fever. Those with rash/fever and myalgias/arthralgias are most likely due to chikungunya fever, dengue fever, or Zika virus. In these arthropod viral transmitted infections, the rash may be pruritic. The case presented here is that of chikungunya fever remarkable for the intensity and duration of her pruritis. PMID:27679755

  14. 基孔肯雅病毒疫苗的研究进展%Advances in research of chikungunya virus vaccine

    Institute of Scientific and Technical Information of China (English)

    陈学敏(综述); 雷迎峰(审校)

    2015-01-01

    Chikungunya fever is a kind of fulminating infectious disease caused by Chikungunya virus, which belongs to Al-phavirus of family Togaviridae.Recently, the virus has been the most significant worldwide public health issues after its re-emergence causing massive outbreaks in a great number of regions around the world.In the absence of a commercially avail-able vaccine or an efficacious anti-CHIKV therapy, we introduce some CHIKV vaccines at the laboratory research stage in this review.%基孔肯雅热是由基孔肯雅病毒( Chikungunya virus,CHIKV)引起的一种急性传染病。基孔肯雅病毒属披膜病毒科甲病毒属。近年来,该病毒死灰复燃,在全球多处引发大规模疫情暴发,是重要的全球性公共卫生问题之一。目前尚无针对CHIKV的疫苗和有效抗病毒药物。疫苗一直是CHIKV研究的热点领域,目前已经取得了很大的进展,就基孔肯雅病毒疫苗的研究进展进行了综述。

  15. Correlation of phylogenetic clade diversification and in vitro infectivity differences among Cosmopolitan genotype strains of Chikungunya virus.

    Science.gov (United States)

    Abraham, Rachy; Manakkadan, Anoop; Mudaliar, Prashant; Joseph, Iype; Sivakumar, Krishnankutty Chandrika; Nair, Radhakrishnan Reghunathan; Sreekumar, Easwaran

    2016-01-01

    Cosmopolitan genotypes of Chikungunya virus caused the large-scale febrile disease outbreaks in the last decade in Asian and African continents. Molecular analyses of these strains had revealed significant genetic diversification and occurrence of novel mosquito-adaptive mutations. In the present study we looked into whether the genetic diversification has implications in the infectivity phenotype. A detailed sequence and phylogenetic analyses of these virus strains of Indian Ocean lineage from Kerala, South India from the years 2008 to 2013 identified three distinct genetic clades (I, II and III), which had presence of clade-specific amino acid changes. The E2 envelope protein of the strains from the years 2012 to 2013 had a K252Q or a novel K252H change. This site is reported to affect mosquito cell infectivity. Most of these strains also had the E2 G82R mutation, a mutation previously identified to increase mammalian cell infectivity, and a novel mutation E2 N72S. Positive selection was identified in four sites in the envelope proteins (E1 K211E, A226V and V291I; E2 K252Q/H). In infectivity analysis, we found that strains from clade III had enhanced cytopathogenicity in HEK293 and Vero cells than by strains representing other two clades. These two strains formed smaller sized plaques and had distinctly higher viral protein expression, infectious virus production and apoptosis induction in HEK293 cells. They had novel mutations R171Q in the nsP1; I539S in nsP2; N409T in nsP3; and N72S in E2. Our study identifies a correlation between phylogenetic clade diversification and differences in mammalian cell infectivity phenotype among Cosmopolitan genotype CHIKV strains. PMID:26611825

  16. Neurovirulence comparison of chikungunya virus isolates of the Asian and East/Central/South African genotypes from Malaysia.

    Science.gov (United States)

    Chiam, Chun Wei; Chan, Yoke Fun; Ong, Kien Chai; Wong, Kum Thong; Sam, I-Ching

    2015-11-01

    Chikungunya virus (CHIKV), an alphavirus of the family Togaviridae, causes fever, polyarthritis and rash. There are three genotypes: West African, Asian and East/Central/South African (ECSA). The latter two genotypes have caused global outbreaks in recent years. Recent ECSA CHIKV outbreaks have been associated with severe neurological disease, but it is not known if different CHIKV genotypes are associated with different neurovirulence. In this study, the neurovirulence of Asian (MY/06/37348) and ECSA (MY/08/065) strains of CHIKV isolated in Malaysia were compared. Intracerebral inoculation of either virus into suckling mice was followed by virus titration, histopathology and gene expression analysis of the harvested brains. Both strains of CHIKV replicated similarly, yet mice infected with MY/06/37348 showed higher mortality. Histopathology findings showed that both CHIKV strains spread within the brain (where CHIKV antigen was localized to astrocytes and neurons) and beyond to skeletal muscle. In MY/06/37348-infected mice, apoptosis, which is associated with neurovirulence in alphaviruses, was observed earlier in brains. Comparison of gene expression showed that a pro-apoptotic gene (eIF2αK2) was upregulated at higher levels in MY/06/37348-infected mice, while genes involved in anti-apoptosis (BIRC3), antiviral responses and central nervous system protection (including CD40, IL-10RA, MyD88 and PYCARD) were upregulated more highly in MY/08/065-infected mice. In conclusion, the higher mortality observed following MY/06/37348 infection in mice is due not to higher viral replication in the brain, but to differentially expressed genes involved in host immune responses. These findings may help to identify therapeutic strategies and biomarkers for neurological CHIKV infections.

  17. Correlation of phylogenetic clade diversification and in vitro infectivity differences among Cosmopolitan genotype strains of Chikungunya virus.

    Science.gov (United States)

    Abraham, Rachy; Manakkadan, Anoop; Mudaliar, Prashant; Joseph, Iype; Sivakumar, Krishnankutty Chandrika; Nair, Radhakrishnan Reghunathan; Sreekumar, Easwaran

    2016-01-01

    Cosmopolitan genotypes of Chikungunya virus caused the large-scale febrile disease outbreaks in the last decade in Asian and African continents. Molecular analyses of these strains had revealed significant genetic diversification and occurrence of novel mosquito-adaptive mutations. In the present study we looked into whether the genetic diversification has implications in the infectivity phenotype. A detailed sequence and phylogenetic analyses of these virus strains of Indian Ocean lineage from Kerala, South India from the years 2008 to 2013 identified three distinct genetic clades (I, II and III), which had presence of clade-specific amino acid changes. The E2 envelope protein of the strains from the years 2012 to 2013 had a K252Q or a novel K252H change. This site is reported to affect mosquito cell infectivity. Most of these strains also had the E2 G82R mutation, a mutation previously identified to increase mammalian cell infectivity, and a novel mutation E2 N72S. Positive selection was identified in four sites in the envelope proteins (E1 K211E, A226V and V291I; E2 K252Q/H). In infectivity analysis, we found that strains from clade III had enhanced cytopathogenicity in HEK293 and Vero cells than by strains representing other two clades. These two strains formed smaller sized plaques and had distinctly higher viral protein expression, infectious virus production and apoptosis induction in HEK293 cells. They had novel mutations R171Q in the nsP1; I539S in nsP2; N409T in nsP3; and N72S in E2. Our study identifies a correlation between phylogenetic clade diversification and differences in mammalian cell infectivity phenotype among Cosmopolitan genotype CHIKV strains.

  18. Molecular characterization of Chikungunya virus isolates from clinical samples and adult Aedes albopictus mosquitoes emerged from larvae from Kerala, South India.

    Science.gov (United States)

    Niyas, Kudukkil P; Abraham, Rachy; Unnikrishnan, Ramakrishnan Nair; Mathew, Thomas; Nair, Sajith; Manakkadan, Anoop; Issac, Aneesh; Sreekumar, Easwaran

    2010-01-01

    Chikungunya virus (CHIKV), an arthritogenic alphavirus, is transmitted to humans by infected Aedes (Ae.) aegypti and Ae.albopictus mosquitoes. In the study, reverse-transcription PCR (RT PCR) and virus isolation detected CHIKV in patient samples and also in adult Ae.albopictus mosquitoes that was derived from larvae collected during a chikungunya (CHIK) outbreak in Kerala in 2009. The CHIKV strains involved in the outbreak were the East, Central and South African (ECSA) genotype that had the E1 A226V mutation. The viral strains from the mosquitoes and CHIK patients from the same area showed a close relationship based on phylogenetic analysis. Genetic characterization by partial sequencing of non-structural protein 2 (nsP2; 378 bp), envelope E1 (505 bp) and E2 (428 bp) identified one critical mutation in the E2 protein coding region of these CHIKV strains. This novel, non-conservative mutation, L210Q, consistently present in both human and mosquito-derived samples studied, was within the region of the E2 protein (amino acids E2 200-220) that determines mosquito cell infectivity in many alpha viruses. Our results show the involvement of Ae. albopictus in this outbreak in Kerala and appearance of CHIKV with novel genetic changes. Detection of virus in adult mosquitoes, emerged in the laboratory from larvae, also points to the possibility of transovarial transmission (TOT) of mutant CHIKV strains in mosquitoes. PMID:20704755

  19. Molecular characterization of Chikungunya virus isolates from clinical samples and adult Aedes albopictus mosquitoes emerged from larvae from Kerala, South India

    Directory of Open Access Journals (Sweden)

    Niyas Kudukkil P

    2010-08-01

    Full Text Available Abstract Chikungunya virus (CHIKV, an arthritogenic alphavirus, is transmitted to humans by infected Aedes (Ae. aegypti and Ae.albopictus mosquitoes. In the study, reverse-transcription PCR (RT PCR and virus isolation detected CHIKV in patient samples and also in adult Ae.albopictus mosquitoes that was derived from larvae collected during a chikungunya (CHIK outbreak in Kerala in 2009. The CHIKV strains involved in the outbreak were the East, Central and South African (ECSA genotype that had the E1 A226V mutation. The viral strains from the mosquitoes and CHIK patients from the same area showed a close relationship based on phylogenetic analysis. Genetic characterization by partial sequencing of non-structural protein 2 (nsP2; 378 bp, envelope E1 (505 bp and E2 (428 bp identified one critical mutation in the E2 protein coding region of these CHIKV strains. This novel, non-conservative mutation, L210Q, consistently present in both human and mosquito-derived samples studied, was within the region of the E2 protein (amino acids E2 200-220 that determines mosquito cell infectivity in many alpha viruses. Our results show the involvement of Ae. albopictus in this outbreak in Kerala and appearance of CHIKV with novel genetic changes. Detection of virus in adult mosquitoes, emerged in the laboratory from larvae, also points to the possibility of transovarial transmission (TOT of mutant CHIKV strains in mosquitoes.

  20. Association of HLA class-I and inhibitory KIR genotypes in Gabonese patients infected by Chikungunya or Dengue type-2 viruses.

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    Caroline Petitdemange

    Full Text Available BACKGROUND: Natural killer (NK cells provide defense in the early stages of the immune response against viral infections. Killer cell immunoglobulin-like receptors (KIR expressed on the surface of NK cells play an important role in regulating NK cell response through recognition of human leukocyte antigen (HLA class I molecules on target cells. Previous studies have shown that specific KIR/ligand combinations are associated with the outcome of several viral infectious diseases. METHODS: We investigated the impact of inhibitory and activating KIR and their HLA-class I ligand genotype on the susceptibility to Chikungunya virus (CHIKV and Dengue virus (DENV2 infections. From April to July 2010 in Gabon, a large outbreak of CHIKV and DENV2 concomitantly occurred in two provinces of Gabon (Ogooué-Lolo and Haut-Ogooué. We performed the genotypic analysis of KIR in the combination with their cognate HLA-class I ligands in 73 CHIKV and 55 DENV2 adult cases, compared with 54 healthy individuals. RESULTS: We found in CHIV-infected patients that KIR2DL1 and KIR2DS5 are significantly increased and decreased respectively, as compared to DENV2+ patients and healthy donors. The combination of KIR2DL1 and its cognate HLA-C2 ligand was significantly associated with the susceptibility to CHIKV infection. In contrast, no other inhibitory KIR-HLA pairs showed an association with the two mosquito-borne arboviruses. CONCLUSION: These observations are strongly suggestive that the NK cell repertoire shaped by the KIR2DL1:HLA-C2 interaction facilitate specific infection by CHIKV.

  1. Laboratory diagnosis and investigation of the first imported Chikungunya fever case in Fujian Province, China%福建省首例输入性基孔肯雅热病例的调查与实验室诊断

    Institute of Scientific and Technical Information of China (English)

    黄萌; 翁育伟; 叶雯婧; 李锋平; 郑友限; 张拥军; 洪思让; 郑奎城; 严延生; 欧剑鸣

    2013-01-01

    目的 通过实验室诊断及流行病学调查证实福建省首例输入性基孔肯雅热病例.方法 调查病例的流行病学史及临床表现,采用病毒核酸检测、测序等方法进行实验室诊断.结果 该病例临床表现符合基孔肯雅热特征,荧光PCR、RT-PCR和测序均证实为基孔肯雅病毒感染.流行病学调查表明,该病例的感染地点在东南亚一带,与扩增的部分病毒序列比对的结果一致.结论 证实福建省首例输入性基孔肯雅热病例,在流行季节亟需加强对重点人群的监测.%Chikungunya fever (CHIK) is a mosquito-borne viral disease that mainly circulating in Southeast Asia and eastern Africa. In this study, to confirm a suspected imported CHIK case in Fujian Province, virus-specific nucleic acid amplification and sequencing were conducted; epidemiological information and clinical features were investigated. Chikungunya virus (CHIKV) infection was identified by real-time RT-PCR, RT-PCR and amplicon sequencing, while the patient's symptoms were in accordance with diagnostic criteria of CHIK. It was indicated by epidemiological data and BLAST analysis of the obtained sequence that the infection was originated from Southeast Asia. Therefore, the first imported CHIK case in Fujian Province was confirmed, extensive surveillance of CHIK should be strengthened.

  2. Chikungunya: Information for the General Public

    Science.gov (United States)

    ... or heart disease • Deaths are rare The mosquitoes • Aedes species mosquitoes transmit chikungunya virus • These same types ... water from outdoor containers o Support local vector control programs • People at increased risk for severe disease ...

  3. Antigenic Variation of East/Central/South African and Asian Chikungunya Virus Genotypes in Neutralization by Immune Sera

    Science.gov (United States)

    Chua, Chong-Long; Sam, I-Ching; Merits, Andres; Chan, Yoke-Fun

    2016-01-01

    Background Chikungunya virus (CHIKV) is a re-emerging mosquito-borne virus which causes epidemics of fever, severe joint pain and rash. Between 2005 and 2010, the East/Central/South African (ECSA) genotype was responsible for global explosive outbreaks across India, the Indian Ocean and Southeast Asia. From late 2013, Asian genotype CHIKV has caused outbreaks in the Americas. The characteristics of cross-antibody efficacy and epitopes are poorly understood. Methodology/Principal Findings We characterized human immune sera collected during two independent outbreaks in Malaysia of the Asian genotype in 2006 and the ECSA genotype in 2008–2010. Neutralizing capacity was analyzed against representative clinical isolates as well as viruses rescued from infectious clones of ECSA and Asian CHIKV. Using whole virus antigen and recombinant E1 and E2 envelope glycoproteins, we further investigated antibody binding sites, epitopes, and antibody titers. Both ECSA and Asian sera demonstrated stronger neutralizing capacity against the ECSA genotype, which corresponded to strong epitope-antibody interaction. ECSA serum targeted conformational epitope sites in the E1-E2 glycoprotein, and E1-E211K, E2-I2T, E2-H5N, E2-G118S and E2-S194G are key amino acids that enhance cross-neutralizing efficacy. As for Asian serum, the antibodies targeting E2 glycoprotein correlated with neutralizing efficacy, and I2T, H5N, G118S and S194G altered and improved the neutralization profile. Rabbit polyclonal antibody against the N-terminal linear neutralizing epitope from the ECSA sequence has reduced binding capacity and neutralization efficacy against Asian CHIKV. These findings imply that the choice of vaccine strain may impact cross-protection against different genotypes. Conclusion/Significance Immune serum from humans infected with CHIKV of either ECSA or Asian genotypes showed differences in binding and neutralization characteristics. These findings have implications for the continued

  4. Vector Competence of Aedes aegypti and Aedes vittatus (Diptera: Culicidae) from Senegal and Cape Verde Archipelago for West African Lineages of Chikungunya Virus

    OpenAIRE

    Diagne, Cheikh T.; Faye, Oumar; Guerbois, Mathilde; Knight, Rachel; Diallo, Diawo; Ba, Yamar; Dia, Ibrahima; Faye, Ousmane; Weaver, Scott C.; Sall, Amadou A; Diallo, Mawlouth

    2014-01-01

    To assess the risk of emergence of chikungunya virus (CHIKV) in West Africa, vector competence of wild-type, urban, and non-urban Aedes aegypti and Ae. vittatus from Senegal and Cape Verde for CHIKV was investigated. Mosquitoes were fed orally with CHIKV isolates from mosquitoes (ArD30237), bats (CS13-288), and humans (HD180738). After 5, 10, and 15 days of incubation following an infectious blood meal, presence of CHIKV RNA was determined in bodies, legs/wings, and saliva using real-time rev...

  5. Identification of novel compounds inhibiting chikungunya virus-induced cell death by high throughput screening of a kinase inhibitor library.

    Directory of Open Access Journals (Sweden)

    Deu John M Cruz

    Full Text Available Chikungunya virus (CHIKV is a mosquito-borne arthrogenic alphavirus that causes acute febrile illness in humans accompanied by joint pains and in many cases, persistent arthralgia lasting weeks to years. The re-emergence of CHIKV has resulted in numerous outbreaks in the eastern hemisphere, and threatens to expand in the foreseeable future. Unfortunately, no effective treatment is currently available. The present study reports the use of resazurin in a cell-based high-throughput assay, and an image-based high-content assay to identify and characterize inhibitors of CHIKV-infection in vitro. CHIKV is a highly cytopathic virus that rapidly kills infected cells. Thus, cell viability of HuH-7 cells infected with CHIKV in the presence of compounds was determined by measuring metabolic reduction of resazurin to identify inhibitors of CHIKV-associated cell death. A kinase inhibitor library of 4,000 compounds was screened against CHIKV infection of HuH-7 cells using the resazurin reduction assay, and the cell toxicity was also measured in non-infected cells. Seventy-two compounds showing ≥50% inhibition property against CHIKV at 10 µM were selected as primary hits. Four compounds having a benzofuran core scaffold (CND0335, CND0364, CND0366 and CND0415, one pyrrolopyridine (CND0545 and one thiazol-carboxamide (CND3514 inhibited CHIKV-associated cell death in a dose-dependent manner, with EC50 values between 2.2 µM and 7.1 µM. Based on image analysis, these 6 hit compounds did not inhibit CHIKV replication in the host cell. However, CHIKV-infected cells manifested less prominent apoptotic blebs typical of CHIKV cytopathic effect compared with the control infection. Moreover, treatment with these compounds reduced viral titers in the medium of CHIKV-infected cells by up to 100-fold. In conclusion, this cell-based high-throughput screening assay using resazurin, combined with the image-based high content assay approach identified compounds against

  6. Versatile Trans-Replication Systems for Chikungunya Virus Allow Functional Analysis and Tagging of Every Replicase Protein.

    Directory of Open Access Journals (Sweden)

    Age Utt

    Full Text Available Chikungunya virus (CHIKV; genus Alphavirus, family Togaviridae has recently caused several major outbreaks affecting millions of people. There are no licensed vaccines or antivirals, and the knowledge of the molecular biology of CHIKV, crucial for development of efficient antiviral strategies, remains fragmentary. CHIKV has a 12 kb positive-strand RNA genome, which is translated to yield a nonstructural (ns or replicase polyprotein. CHIKV structural proteins are expressed from a subgenomic RNA synthesized in infected cells. Here we have developed CHIKV trans-replication systems, where replicase expression and RNA replication are uncoupled. Bacteriophage T7 RNA polymerase or cellular RNA polymerase II were used for production of mRNAs for CHIKV ns polyprotein and template RNAs, which are recognized by CHIKV replicase and encode for reporter proteins. CHIKV replicase efficiently amplified such RNA templates and synthesized large amounts of subgenomic RNA in several cell lines. This system was used to create tagged versions of ns proteins including nsP1 fused with enhanced green fluorescent protein and nsP4 with an immunological tag. Analysis of these constructs and a matching set of replicon vectors revealed that the replicases containing tagged ns proteins were functional and maintained their subcellular localizations. When cells were co-transfected with constructs expressing template RNA and wild type or tagged versions of CHIKV replicases, formation of characteristic replicase complexes (spherules was observed. Analysis of mutations associated with noncytotoxic phenotype in CHIKV replicons showed that a low level of RNA replication is not a pre-requisite for reduced cytotoxicity. The CHIKV trans-replicase does not suffer from genetic instability and represents an efficient, sensitive and reliable tool for studies of different aspects of CHIKV RNA replication process.

  7. High rates of co-infection of Dengue and Chikungunya virus in Odisha and Maharashtra, India during 2013.

    Science.gov (United States)

    Saswat, Tanuja; Kumar, Abhishek; Kumar, Sameer; Mamidi, Prabhudutta; Muduli, Sagarika; Debata, Nagen Kumar; Pal, Niladri Shekhar; Pratheek, B M; Chattopadhyay, Subhasis; Chattopadhyay, Soma

    2015-10-01

    Dengue viral (DENV) infection is endemic in different parts of India and because of similar primary signs and symptoms, Chikungunya virus (CHIKV) is mostly undiagnosed. Hence, we investigated 204 suspected Dengue cases in a hospital based cross-sectional study in Odisha, India in 2013. It was observed that 50 samples were positive for DENV only, 28 were positive for CHIKV only and interestingly, 28 patients were co-infected with both DENV and CHIKV. Additionally, a total of 18 confirmed Dengue samples from Maharashtra, India were screened for CHIKV and out of those, 15 were co-infected. All CHIKV strains were of East Central South African (ECSA) type and serotype 2 (genotype IV) was predominant in the DENV samples. Additionally, Dengue serotype 1 and 3 were also detected during this time. Further, sequence analysis of E1 gene of CHIKV strains revealed that two substitution mutations (M269V and D284E) were observed in almost 50% strains and they were from co-infected patients. Similarly, sequence analysis of C-prM gene showed the presence of five substitution mutations, (G70S, L72F, N90S, S93N and I150L) in all serotype 1 and two consistent mutations (A101V and V112A) in serotype 2 Dengue samples. Together, it appears that a significantly high number of dengue patients (43, 44.8%) were co-infected with DENV and CHIKV during this study. This emphasizes the need of a routine diagnosis of CHIKV along with DENV for febrile patients. This will be useful in early and proper recognition of infecting pathogen to study the correlation of clinical symptoms with single or co-infection which will ultimately help to implement proper patient care in future.

  8. Simultaneous detection of West Nile virus and Chikungunya virus by duplex real-time quantitative PCR%双重荧光定量PCR检测西尼罗病毒和基孔肯雅病毒

    Institute of Scientific and Technical Information of China (English)

    余蓓蓓; 卢亦愚; 谢鑫友; 徐昌平; 张钧

    2013-01-01

    目的 建立同时检测西尼罗病毒(WNV)、基孔肯雅病毒(CHIKV)的双重荧光定量PCR法,为临床疑似病例的诊断提供依据.方法 分别针对WNV CAP基因、CHIKV E1基因保守区设计特异性引物和TaqMan探针,建立并优化双重荧光定量PCR反应体系,评价方法的特异性和灵敏度.结果 建立的双重荧光定量PCR可同时检测WNV、CHIKV核酸,标准曲线相关系数(r)分别达0.999、0.998,灵敏度达10 copies/μL,具有良好的特异性.结论 建立了同时检测WNV、CHIKV的双重荧光定量PCR法,但尚需临床进一步验证.%Objective To develop a duplex real-time quantitative PCR assay for simultaneous detection of West Nile virus and Chikungunya virus.Methods Two sets of primers and TaqMan probes were designed based on highly conserved CAP gene region of West Nile virus and E1 gene region of Chikungunya virus,and the reactive condition of duplex real-time PCR was optimized.The sensitivity and specificity of the assay were evaluated.Results The duplex real-time quantitative PCR assay showed excellent specificity in simultaneous detection of West Nile virus and Chikungunya virus.The sensitivities of the assay were 10 copies/μL for both the virus,and the correlation coefficient of the quantitative curve were 0.999 and 0.998 respectively.Conclusion The duplex fluorescent quantitative PCR assay developed in this study is sensitive and specific for simultaneous detection of West Nile virus and Chikungunya virus.The efficiency of the assay for detecting of clinical samples should be further evaluated.

  9. Prospective study of Chikungunya virus acute infection in the Island of La Reunion during the 2005-2006 outbreak.

    Directory of Open Access Journals (Sweden)

    Frederik Staikowsky

    Full Text Available BACKGROUND: Chikungunya virus (CHIKV is a recently re-emerged arthropod borne virus responsible for a massive outbreak in the Indian Ocean and India, and extended to Southeast Asia as well as Italy. CHIKV has adapted to Aedes albopictus, an anthropophilic mosquito species widely distributed in Asia, Europe, Africa and America. Our objective was to determine the clinical and biological features of patients at the acute phase of CHIKV infection. METHODS AND FINDINGS: A prospective study enrolled 274 consecutive patients with febrile arthralgia recorded at the Emergency Department of the Groupe Hospitalier Sud-Réunion between March and May 2006. Three groups were defined: one group of 180 viremic patients (positive CHIKV RT-PCR, one group of 34 patients with acute post-viremic infection (negative CHIKV RT-PCR, positive anti-CHIKV IgM and negative IgG, and one group of 46 uninfected patients (negative CHIKV RT-PCR, anti-CHIKV IgM and IgG. Bivariate analyses of clinical and biological features between groups were performed. Patients with CHIKV viremia presented typically with asymmetrical bilateral polyarthralgia (96.5% affecting the lower (98% and small joints (74.8%, as well as asthenia (88.6%, headache (70%, digestive trouble (63.3%, myalgia (59%, exanthems (47.8%, conjunctival hyperhemia (23% and adenopathy (8.9%. Vertigo, cutaneous dysesthesia, pharyngitis and haemorrhages were seldom observed. So far unreported symptoms such as chondrocostal arthralgia (20%, entesopathies (1.6%, talalgia (14% were also noted. Prurit was less frequent during the viremic than post-viremic phase (13.9% vs. 41.2%; p<0.001, whereas lymphopenia was more frequent (87.6% vs. 39.4%; p<0.001. Others biological abnormalities included leukopenia (38.3%, thrombocytopenia (37.3%, increased ASAT and ALAT blood levels (31.6 and 7.3%, respectively and hypocalcemia (38.7%. Lymphopenia <1,000/mm(3 was very closely associated with viremic patients (Yule coefficient 0.82, positive

  10. [The chikungunya epidemic in the Caribbean: implications for travellers and physicians].

    Science.gov (United States)

    Cleton, Natalie B; Reusken, Chantal B E M; van Gorp, Eric C M

    2014-01-01

    In 2013, the first autochthonous cases of the chikungunya virus (CHIKV) were reported on the Caribbean island of Saint Martin. The chikungunya virus has since become endemic in the Caribbean due to autochthonous transmission. In the presence of fever and joint symptoms in any traveller returning from the Caribbean, CHIKV should be considered. Although symptoms resemble those of dengue fever, the course of chikungunya is milder. Chikungunya much more commonly causes chronic joint pain. Laboratory tests for the chikungunya virus may give false positive results due to cross reactions with closely related viruses, so taking a full disease and travel history from the patient is necessary in order to interpret these test results correctly. There is no specific treatment for the chikungunya virus. A correct diagnosis can prevent unnecessary additional tests and unjustified treatment. The chikungunya virus can be prevented by the use of insect-repelling substances, nets and air-conditioning. PMID:25269640

  11. Chikungunya Fever: Case Report in Los Angeles, California

    Directory of Open Access Journals (Sweden)

    Katherine R. Harter

    2014-11-01

    Full Text Available We report the case of a 33-year-old woman returning from Haiti, presenting to our emergency department (ED with fever, rash and arthralgia. Following a broad workup that included laboratory testing for dengue and malaria, our patient was diagnosed with Chikungunya virus, which was then reported to the Centers for Disease Control and Prevention for initiation of infection control. This case demonstrates the importance of the ED for infectious disease case identification and initiation of public health measures. This case also addresses public health implications of Chikungunya virus within the United States, and issues related to the potential for local spread and autochthonous cases. [West J Emerg Med. 2014;15(7:-0.

  12. Aedes hensilli as a Potential Vector of Chikungunya and Zika Viruses

    OpenAIRE

    Ledermann, Jeremy P.; Laurent Guillaumot; Lawrence Yug; Steven C Saweyog; Mary Tided; Paul Machieng; Moses Pretrick; Maria Marfel; Anne Griggs; Martin Bel; Duffy, Mark R.; W Thane Hancock; Tai Ho-Chen; Ann M Powers

    2014-01-01

    An epidemic of Zika virus (ZIKV) illness that occurred in July 2007 on Yap Island in the Federated States of Micronesia prompted entomological studies to identify both the primary vector(s) involved in transmission and the ecological parameters contributing to the outbreak. Larval and pupal surveys were performed to identify the major containers serving as oviposition habitat for the likely vector(s). Adult mosquitoes were also collected by backpack aspiration, light trap, and gravid traps at...

  13. Dengue and chikungunya: long-distance spread and outbreaks in naïve areas.

    Science.gov (United States)

    Rezza, Giovanni

    2014-12-01

    Mosquito-borne virus infections, such as dengue and chikungunya, are continuously expanding their geographical range. The dengue virus, which is known to be a common cause of febrile illness in tropical areas of the Old World, is now widespread in the Americas. In most affected areas, all the four dengue virus serotypes have circulated. Recently, small clusters of dengue have been identified also in Southern Europe during the hot season. The chikungunya virus, initially restricted to Central Africa, where is a common cause of sporadic cases or small outbreaks, and Asia, where it is used to cause large epidemics, has recently invaded new territories. After ravaging Indian Ocean Islands and the Indian subcontinent, CHIKV caused an outbreak in north-eastern Italy. Recently, chikungunya has reached the Caribbean, causing for the first time a large epidemic on the American continent. Although Aedes aegypti is the main vector of both viruses, Aedes albopictus, the Asian 'Tiger' mosquito, is now playing an increasingly important role, contributing to their spread in temperate climate areas. Hereby, we focus the attention on outbreaks of dengue and chikungunya occurring in previously disease-free areas and discuss factors associated with the long-distance spread of the vector-borne infections, such as mutations increasing viral fitness, climate change, urbanization, and globalization of humans and vectors. PMID:25491436

  14. [[Virus-like particle-based immunoglobulin M capture enzyme-linked immunosorbent assay for the detection of IgM antibodies against Chikungunya virus].

    Science.gov (United States)

    Li, Jian-dong; Zhang, Quan-fu; Zhang, Shuo; Li, Chuan; Liu, Qin-zhi; Liang, Mi-fang; Li, De-xin

    2014-11-01

    To establish a MacELISA method for the detection of IgM antibodies against Chikungunya virus (CHIKV), we prepared virus like particle (VLP) antigens of CHIKV using the whole structural protein C-E3-E2-6K-E1 encoding gene with a baculovirus expression system in Sf9 insect cells. The VLPs were purified and used to immunize Kunming mice. Then, polyclonal antibodies were purified from the samples of ascites with a protein G HiTrap SP column and labeled with horseradish peroxidase. A MacELISA method for the detection of IgM antibodies against CHIKV was assembled with goat anti-human IgM antibody, VLP antigens and an enzyme-labeled polyclonal antibody. The results were evaluated with a serum panel containing serum samples from laboratory-confirmed CHIK, HFRS patients, healthy donors, and commercially available CHIKV IgM as a quality control. It was shown that the MacELISA had a specificity of 99% (99/100), the coefficients of variation (CoV) within a plate were ELISA plates in terms of the plate variation coefficient was <15%. A comparative analysis was performed to compare the current method against a commercial CHIKV IgM antibody detection kit for IIFA-IgM. The detection limit of MacELISA was significantly lower than that of the IIFA-IgM commercial kit (P< 0.0001). Here, we demonstrate that the VLP-based MacELISA is a promising tool for the early diagnosis and epidemiological investigation of CHIKV infection, with a high level of sensitivity and specificity for the detection of IgM antibodies against CHIKV.

  15. 基孔肯雅病毒荧光定量PCR检测方法的建立%Real-time PCR method for rapid detection of Chikungunya virus

    Institute of Scientific and Technical Information of China (English)

    杨宇; 白琳; 胡健萍; 姚李四; 魏莲; 杨志红; 王静

    2012-01-01

    Objective To establish a rapid, sensitive and specific detection method for detecting Chikungunya virus(CHIKV) using Real-time fluorescence quantitative PCR. Methods With specifically designed primers and a TaqMan probe on the highly conserved sequence of CHIKV through alignment, the sensitivity of the Real - time fluorescence quantitative PCR assay was optimized by evaluating different concentrations of primers and probes. Results A specific Real - time PCR method was developed with the sensitivity of 21 copies/μl for CHIKV, a synthetic CHIKV genome DNA as a positive control; Japanese encephalitis virus, Yellow fever virus, Dengue virus were using to examine the specificity. Conclusion Promising prospects of this assay could be expected for Chikungunya fever prevention and control.%目的 建立一种快速、敏感、特异的实时荧光定量PCR方法,检测基孔肯雅病毒.方法 通过序列比对挑选出基孔肯雅病毒基因组中高度保守的序列,在此序列上设计引物及TaqMan探针,建立实时荧光定量PCR反应体系.结果 经优化的荧光定量PCR方法有较好的灵敏度和特异性,对阳性对照质粒标准品的灵敏度可达21拷贝/μl,通过检测与传播媒介相似的流行性乙型脑炎病毒、黄热病毒、登革热病毒无交叉反应.结论 该方法的建立在基孔肯雅热的疾病防控方面有较好的应用前景.

  16. A sensitive epitope-blocking ELISA for the detection of Chikungunya virus-specific antibodies in patients

    NARCIS (Netherlands)

    Goh, L.Y.H.; Kam, Y.W.; Metz, S.W.H.; Hobson-Peters, J.; Prow, N.A.; McCarthy, S.; Smith, D.W.; Pijlman, G.P.; Ng, L.F.P.; Hall, R.A.

    2015-01-01

    Chikungunya fever (CHIKF) has re-emerged as an arboviral disease that mimics clinical symptoms of other diseases such as dengue, malaria, as well as other alphavirus-related illnesses leading to problems with definitive diagnosis of the infection. Herein we describe the development and evaluation of

  17. Inhibition of chikungunya virus by picolinate that targets viral capsid protein.

    Science.gov (United States)

    Sharma, Rajesh; Fatma, Benazir; Saha, Amrita; Bajpai, Sailesh; Sistla, Srinivas; Dash, Paban Kumar; Parida, Manmohan; Kumar, Pravindra; Tomar, Shailly

    2016-11-01

    The protein-protein interactions (PPIs) of the transmembrane glycoprotein E2 with the hydrophobic pocket on the surface of capsid protein (CP) plays a critical role in alphavirus life cycle. Dioxane based derivatives targeting PPIs have been reported to possess antiviral activity against Sindbis Virus (SINV), the prototype alphavirus. In this study, the binding of picolinic acid (PCA) to the conserved hydrophobic pocket of capsid protein was analyzed by molecular docking, isothermal titration calorimetry (ITC), surface plasmon resonance (SPR) and fluorescence spectroscopy. The binding constant KD obtained for PCA was 2.1×10(-7)M. Additionally, PCA significantly inhibited CHIKV replication in infected Vero cells, decreasing viral mRNA and viral load as assessed by qRT-PCR and plaque reduction assay, respectively. This study is suggestive of the potential of pyridine ring compounds as antivirals against alphaviruses and may serve as the basis for the development of PCA based drugs against alphaviral diseases.

  18. Progress on Detecting Methods of Chikungunya Virus%基孔肯雅病毒检测方法及进展

    Institute of Scientific and Technical Information of China (English)

    吴忠华; 秦秀英; 罗鹏

    2014-01-01

    Chikungunya virus(CHIKV) was the pathogen of Chikungunya fever transmitted by aedes mosquitoes. Clinical symptoms of the patients were characterized by fever, skin rash and arthralgia. CHIKV mainly distributes in Africa and Southeast Asia, and recently caused a pandemic in Indian Ocean region. In China, emerged as im⁃ported cases, CHIKV had not triggered a break-out yet. This article summarized the progress of detecting methods of CHIKV.%基孔肯雅病毒是引起基孔肯雅热的病原体,主要经伊蚊传播,感染者的症状主要以发热、皮疹和关节疼痛为主。该病毒主要分布在非洲、东南亚等地区,近年来在印度洋地区造成大规模流行。我国主要以输入性病例为主,未发生大规模流行。对基孔肯雅病毒的实验室检测方法及最新研究进展进行了综述。

  19. Use of Household Cluster Investigations to Identify Factors Associated with Chikungunya Virus Infection and Frequency of Case Reporting in Puerto Rico

    Science.gov (United States)

    Bloch, Danielle; Roth, Nicole M.; Caraballo, Elba V.; Muñoz-Jordan, Jorge; Hunsperger, Elizabeth; Rivera, Aidsa; Pérez-Padilla, Janice; Rivera Garcia, Brenda

    2016-01-01

    Background Chikungunya virus (CHIKV) is transmitted by Aedes species mosquitoes and is the cause of an acute febrile illness characterized by potentially debilitating arthralgia. After emerging in the Caribbean in late 2013, the first locally-acquired case reported to public health authorities in Puerto Rico occurred in May 2014. During June–August 2014, household-based cluster investigations were conducted to identify factors associated with infection, development of disease, and case reporting. Methodology/Principal Findings Residents of households within a 50-meter radius of the residence of laboratory-positive chikungunya cases that had been reported to Puerto Rico Department of Health (PRDH) were offered participation in the investigation. Participants provided a serum specimen and answered a questionnaire that collected information on demographic factors, household characteristics, recent illnesses, healthcare seeking behaviors, and clinical diagnoses. Current CHIKV infection was identified by rRT-PCR, and recent CHIKV infection was defined by detection of either anti-CHIKV IgM or IgG antibody. Among 250 participants, 74 (30%) had evidence of CHIKV infection, including 12 (5%) with current and 62 (25%) with recent CHIKV infection. All specimens from patients with CHIKV infection that were collected within four days, two weeks, and three weeks of illness onset were positive by RT-PCR, IgM ELISA, and IgG ELISA, respectively. Reporting an acute illness in the prior three months was strongly associated with CHIKV infection (adjusted odds ratio [aOR] = 21.6, 95% confidence interval [CI]: 9.24–50.3). Use of air conditioning (aOR = 0.50, 95% CI = 0.3–0.9) and citronella candles (aOR = 0.4, 95% CI = 0.1–0.9) were associated with protection from CHIKV infection. Multivariable analysis indicated that arthralgia (aOR = 51.8, 95% CI = 3.8–700.8) and skin rash (aOR = 14.2, 95% CI = 2.4–84.7) were strongly associated with CHIKV infection. Hierarchical cluster

  20. Rapid and real-time detection technologies for emerging viruses of biomedical importance

    Indian Academy of Sciences (India)

    M M Parida

    2008-11-01

    The development of technologies with rapid and sensitive detection capabilities and increased throughput have become crucial for responding to greater number threats posed by emerging and re-emerging viruses in the recent past. The conventional identification methods require time-consuming culturing, and/ or detection of antibodies, which are not very sensitive and specific. The recent advances in molecular biology techniques in the field of genomics and proteomics greatly facilitate the rapid identification with more accuracy. We have developed two real-time assays i.e., SYBR green I based real time reverse transcription polymerase chain reaction (RT-PCR) and RT-loop-mediated isothermal amplification (LAMP) assay for rapid detection as well as typing of some of the emerging viruses of biomedical importance viz. dengue, Japanese encephalitis, chikungunya, west Nile, severe acute respiratory syndrome virus (SARS) etc. Both these techniques are capable of detection and differentiation as well as quantifying viral load with higher sensitivity, rapidity, specificity. One of the most important advantages of LAMP is its field applicability, without requirement of any sophisticated equipments. Both these assays have been extensively evaluated and validated with clinical samples of recent epidemics from different parts of India. The establishment of these real time molecular assays will certainly facilitate the rapid detection of viruses with high degree of precision and accuracy in future.

  1. Pan-European Chikungunya surveillance: designing risk stratified surveillance zones.

    Science.gov (United States)

    Tilston, Natasha; Skelly, Chris; Weinstein, Phil

    2009-01-01

    The first documented transmission of Chikungunya within Europe took place in Italy during the summer of 2007. Chikungunya, a viral infection affecting millions of people across Africa and Asia, can be debilitating and no prophylactic treatment exists. Although imported cases are reported frequently across Europe, 2007 was the first confirmed European outbreak and available evidence suggests that Aedes albopictus was the vector responsible and the index case was a visitor from India. This paper proposed pan-European surveillance zones for Chikungunya, based on the climatic conditions necessary for vector activity and viral transmission. Pan-European surveillance provides the best hope for an early-warning of outbreaks, because national boundaries do not play a role in defining the risk of this new vector borne disease threat. A review of climates, where Chikungunya has been active, was used to inform the delineation of three pan-European surveillance zones. These vary in size each month across the June-September period of greatest risk. The zones stretch across southern Europe from Portugal to Turkey. Although the focus of this study was to define the geography of potential surveillance zones based on the climatic limits on the vector and virus, a preliminary examination of inward bound airline passengers was also undertaken. This indicated that France and Italy are likely to be at greater risk due to the number of visitors they receive from Chikungunya active regions, principally viraemic visitors from India. Therefore this study represents a first attempt at creating risk stratified surveillance zones, which we believe could be usefully refined with the use of higher resolution climate data and more complete air travel data. PMID:19878588

  2. Pan-European Chikungunya surveillance: designing risk stratified surveillance zones

    Directory of Open Access Journals (Sweden)

    Skelly Chris

    2009-10-01

    Full Text Available Abstract The first documented transmission of Chikungunya within Europe took place in Italy during the summer of 2007. Chikungunya, a viral infection affecting millions of people across Africa and Asia, can be debilitating and no prophylactic treatment exists. Although imported cases are reported frequently across Europe, 2007 was the first confirmed European outbreak and available evidence suggests that Aedes albopictus was the vector responsible and the index case was a visitor from India. This paper proposed pan-European surveillance zones for Chikungunya, based on the climatic conditions necessary for vector activity and viral transmission. Pan-European surveillance provides the best hope for an early-warning of outbreaks, because national boundaries do not play a role in defining the risk of this new vector borne disease threat. A review of climates, where Chikungunya has been active, was used to inform the delineation of three pan-European surveillance zones. These vary in size each month across the June-September period of greatest risk. The zones stretch across southern Europe from Portugal to Turkey. Although the focus of this study was to define the geography of potential surveillance zones based on the climatic limits on the vector and virus, a preliminary examination of inward bound airline passengers was also undertaken. This indicated that France and Italy are likely to be at greater risk due to the number of visitors they receive from Chikungunya active regions, principally viraemic visitors from India. Therefore this study represents a first attempt at creating risk stratified surveillance zones, which we believe could be usefully refined with the use of higher resolution climate data and more complete air travel data.

  3. Chikungunya Virus Infections Among Patients with Dengue-Like Illness at a Tertiary Care Hospital in the Philippines, 2012-2013.

    Science.gov (United States)

    Velasco, John Mark; Valderama, Maria Theresa; Lopez, Maria Nila; Chua, Domingo; Latog, Rene; Roque, Vito; Corpuz, June; Klungthong, Chonticha; Rodpradit, Prinyada; Hussem, Kittinun; Poolpanichupatam, Yongyuth; Macareo, Louis; Fernandez, Stefan; Yoon, In-Kyu

    2015-12-01

    Chikungunya virus (CHIKV) often co-circulates with dengue virus (DENV). A cross-sectional surveillance study was conducted at a tertiary hospital in Manila, Philippines, to describe the prevalence and characteristics of DENV and CHIKV infections among patients seeking care for dengue-like illness. Acute blood samples from patients ≥ 6 months of age clinically diagnosed with dengue from November 2012 to December 2013 underwent reverse transcription polymerase chain reaction (RT-PCR) to detect DENV and CHIKV RNA. A total of 118 patients with clinically diagnosed dengue (age range = 1-89 years, mean = 22 years; male-to-female ratio = 1.51) were tested by DENV RT-PCR; 40 (34%) were DENV PCR-positive (age range = 1-45 years, mean = 17 years). All DENV serotypes were detected: 11 (28%) DENV-1, 6 (15%) DENV-2, 6 (15%) DENV-3, and 17 (42%) DENV-4. Of 112 patients clinically diagnosed with dengue and tested by CHIKV RT-PCR, 11 (10%) were CHIKV PCR-positive (age range = 2-47 years, mean = 20.3 years). No coinfections were detected. Presenting signs/symptoms did not differ between DENV- and CHIKV-positive cases. Sequencing of envelope 1 gene from two CHIKV PCR-positive samples showed Asian genotype. This study highlights the potential for misdiagnosis of medically attended CHIKV infections as DENV infection and the difficulty in clinically differentiating dengue and chikungunya based on presenting signs/symptoms alone. This underscores the necessity for diagnostic laboratory tests to distinguish CHIKV infections in the background of actively co-circulating DENV.

  4. 基孔肯亚病毒和辛德毕斯病毒检测基因芯片的建立%Establishment and application of gene chip for Chikungunya virus and Sindbis virus

    Institute of Scientific and Technical Information of China (English)

    凡敏; 田明尧; 赵权; 郭欢欢; 任静强; 刘昊; 刘振江; 岳云强; 袁森; 崔鹤馨; 鲁会军; 田宇飞; 金宁一

    2012-01-01

    The microarray was established to detect Chikungunya virus and Sindbis virus with strong specific and high sensitivity.According to the conservative gene sequences of Chikungunya virus and Sindbis virus in GenBank,the E gene sequences of these two viruses and their primers were synthesized,and the oligonucleotide probes were designed based on the two virus,specific detection microarray was prepared.And its sensitivity,specificity and reproducibility were examined.The results showed that the sensitivity of this microarray was 100 times higher than ordinary PCR method.This microarray was specific for Chikungunya virus and Sindbis virus,which did not cross-react with other viruses such as Japanese encephalitis virus.This study established a microarray for detection of Chikungunya virus and Sindbis virus with high sensitivity and specificity,and it is suitable to epidemiological studies and species-specific detection.%根据GenBank中收录的基孔肯亚病毒和辛德毕斯病毒基因的保守序列,合成2种病毒E基因序列及引物,设计针对2种病毒的寡核苷酸探针,制备基孔肯亚病毒与辛德毕斯病毒特异性检测基因芯片,并对该芯片的灵敏性、特异性和重复性进行了验证。结果显示,所建立基因芯片检测方法的灵敏度是普通PCR方法的100倍。利用所制备的基因芯片,能检测到基孔肯亚病毒和辛德毕斯病毒特异性杂交信号,阴性对照病毒(基因Ⅰ型流行性乙型脑炎病毒,基因Ⅲ型流行性乙型脑炎病毒,猪繁殖与呼吸综合征病毒及流感病毒)均无杂交信号。本试验初步建立了基孔肯亚病毒与辛德毕斯病毒特异性基因芯片检测方法,该方法灵敏度高、特异性强,适用于基孔肯亚病毒与辛德毕斯病毒的流行病学调查和种特异性鉴定。

  5. Presence and distribution of economically important potato viruses in Montenegro

    OpenAIRE

    Jelena Zindović

    2011-01-01

    The research was carried out, in the period 2002-2004 in order to determine the presence and distribution of potato viruses at 12 different locations and on 9 different potato varieties grown in Montenegro. The research included collecting of samples in seed potato crops and testing of six economically important potato viruses: Potato leaf roll virus (PLRV), Potato virus Y (PVY), Potato virus X (PVX), Potato virus S (PVS), Potato virus A (PVA) i Potato viru...

  6. 中国首例输入性基孔肯雅热临床分析%Clinicial analysis of the first imported ease of Chikungunya fever in China

    Institute of Scientific and Technical Information of China (English)

    蔡卫平; 张复春; 曹欣; 王建; 陈劲峰; 魏绍静

    2008-01-01

    Objective To investigate the epidemiological, clinical and pathogenic characteristics and prognosis of the first imported case of Chikungunya fever in China in 2008. Methods Epidemiological and clinical data of this mate adult patient were analyzed retrospectively. Chikungunya virus (CHIKV)-IgM was detected using enzyme linked immunosorbent assay (ELISA) and colloidal gold immunoassay. CHIKV-RNA was detected using real-time fluorescent polymerase chain reaction (RT-PCR). Results This patient had onset of fever on March 2 in 2008 and lasted for 5 days. In addition, he felt joint and muscle pains, headache and found generalized engorged maculopapule. The laboratory tests showed leukopenia and thrombocytopenia. CHIKV-IgM was detected positive at day 9 after the onset and CHIKV-RNA was all positive at day 3, 5, 7, 9 after the onset. A 575 bp fragment of RT-PCR product was sequenced and detected the nucleotide homology was 99% compared with CHIKV sequences in GenBank. The patient recovered with symptomatic supportive treatment.Conclusion This imported case of Chikungunya virus infection is reported for the first time in China.It shows similar clinical manifestations with dengue fever.%目的 了解2008年我国首例输入性基孔肯雅热病例的流行病学、临床、病原学特点及预后转归.方法 对1例成年男性患者流行病学及临床资料进行回顾性分析,并采用ELISA和胶体合法检测患者血清基孔肯雅病毒IgM(CHIKV-IgM)抗体,实时荧光PCR法检测基孔肯雅病毒核酸(CHIKV RNA).结果 该患者临床表现为发热起病,有头痛、全身肌肉及关节酸痛,全身充血性斑丘疹,WBC及PLT减少.发病第9天CHIKV-IgM阳性;第3、5,7、9天CHIKV RNA阳性;RT-PCR扩增产物为575个核苷酸碱基片段,经序列测序结果与基孔肯雅病毒核酸序列同源性高达99%.患者经对症支持等治疗痊愈出院.结论 该患者为我国首例输入性基孔肯雅热确诊病例,本病临床表现与登革热相似.

  7. False positive dengue NS1 antigen test in a traveller with an acute Zika virus infection imported into Switzerland.

    Science.gov (United States)

    Gyurech, Danielle; Schilling, Julian; Schmidt-Chanasit, Jonas; Cassinotti, Pascal; Kaeppeli, Franz; Dobec, Marinko

    2016-01-01

    We report the first case of an acute Zika virus infection imported into Switzerland by a traveller returning from Canoa Quebrada, Ceará state, in the north-eastern part of Brazil. Due to a false positive dengue virus NS1 antigen test, IgG antibody seroconversion and a suggestive clinical picture,an acute dengue fever was initially considered. However, because of lack of specific IgM-antibodies, stationary IgG antibody titre and a negative dengue virus PCR test result, a dengue virus infection was excluded and a cross-reaction with other, causative flaviviruses was postulated. Based on recent reports of Zika fever cases in the north-eastern parts of Brazil, an acute Zika virus infection was suspected. Because of a lack of commercially available Zika virus diagnostic tests, the case was confirmed in the WHO reference laboratory. As the clinical presentation of Zika virus infection can be confused with dengue fever and chikungunya fever, and because of possible public health implications, all patients returning from affected areas should be additionally tested for Zika virus. This case illustrates the urgent medical need for a broadly available assay capable of differentiating Zika from Dengue infections.

  8. A Role for RNA Viruses in the Pathogenesis of Burkitt's Lymphoma: The Need for Reappraisal

    Directory of Open Access Journals (Sweden)

    Corry van den Bosch

    2012-01-01

    Full Text Available Certain infectious agents are associated with lymphomas, but the strength of the association varies geographically, suggesting that local environmental factors make important contributions to lymphomagenesis. Endemic Burkitt’s Lymphoma has well-defined environmental requirements making it particularly suitable for research into local environmental factors. The Epstein-Barr virus and holoendemic Malaria are recognized as important cofactors in endemic Burkitt’s Lymphoma and their contributions are discussed. Additionally, infection with Chikungunya Fever, a potentially oncogenic arbovirus, was associated with the onset of endemic Burkitt’s Lymphoma in one study and also with space-time case clusters of the lymphoma. Chikungunya Virus has several characteristics typical of oncogenic viruses. The Flavivirus, Hepatitis C, a Class 1 Human Carcinogen, closely related to the arboviruses, Yellow Fever, and Dengue, is also more distantly related to Chikungunya Virus. The mechanisms of oncogenesis believed to operate in Hepatitis C lymphomagenesis are discussed, as is their potential applicability to Chikungunya Virus.

  9. 深圳市输入性基孔肯雅热病例的流行病学和病原学特征分析%Analysis on the epidemiology and etiologic characteristics of first imported Chikungunya fever case in Shenzhen in 2010

    Institute of Scientific and Technical Information of China (English)

    阳帆; 许少坚; 张仁利; 谢旭; 何雅青; 黄达娜; 武伟华; 李玥

    2015-01-01

    Objective To study the epidemiology and the etiology characteristics of first imported Chikungunya fever case reported in Shenzhen city in 2010.Methods Data on descriptive epidemiology was collected to study the characteristics to the epidemic.The serum sample collected from the suspect Chikungunya fever case was detected for IgM,IgG by ELISA and Chikungunya virus nucleic acid by realtime RT-PCR.The samples were further inoculated in BHK-21 cells for virus isolation.Structural polyprotein gene (C-E3-E2-6K-E1) of isolated virus strain was amplified by RT-PCR and sequenced to construct homology comparison and phylogenetic tree of E1 gene of Shenzhen CHIKV with the strains isolated from other areas.Results The case was laboratory confirmed imported Chikungunya fever cases in Shenzhen on October 2010.IgM antibody and RNA of Chikungunya virus were detected in the serum sample.Chikungunya virus named CHIKV-SZ1050 was successfully isolated from the serum sample for the first time.The homology of nucleotide sequence of E1 gene of SZ1050 with African prototype S27 strain,GD05/2010 strain,TN06310 strain were 98.2%,98.3% and 98.7%,respectively.The phylogenetic tree indicated that SZ1050 was most close to GZ1029 strain,next to TN06310 strain.The isolated Chikungunya virus belonged to genotype ECSA.Conclusion The virological,serological and molecular features showed that the imported case of Chikungunya fever in 2010 was caused by CHIKV ECSA genotype and genetic characteristics of the SZ1050 virus strain are consistent with CHIKV popular in India.This imported case did not cause the secondary cases.%目的 对深圳市2010年首例基孔肯雅热疫情及病原学特征进行分析.方法 调查分析流行病学特点;对疑似患者血清标本采用ELISA和荧光PCR方法分别检测病毒IgM、IgG抗体和核酸,并用BHK-21细胞分离病毒.采用RT-PCR方法扩增病毒结构蛋白基因后进行序列测定,并与不同国家和地区的基孔肯雅毒

  10. Sero-prevalence and cross-reactivity of chikungunya virus specific anti-E2EP3 antibodies in arbovirus-infected patients.

    Directory of Open Access Journals (Sweden)

    Yiu-Wing Kam

    2015-01-01

    Full Text Available Chikungunya virus (CHIKV and clinically-related arboviruses cause large epidemics with serious economic and social impact. As clinical symptoms of CHIKV infections are similar to several flavivirus infections, good detection methods to identify CHIKV infection are desired for improved treatment and clinical management. The strength of anti-E2EP3 antibody responses was explored in a longitudinal study on 38 CHIKV-infected patients. We compared their anti-E2EP3 responses with those of patients infected with non-CHIKV alphaviruses, or flaviviruses. E2EP3 cross-reactive samples from patients infected with non-CHIKV viruses were further analyzed with an in vitro CHIKV neutralization assay. CHIKV-specific anti-E2EP3 antibody responses were detected in 72% to 100% of patients. Serum samples from patients infected with other non-CHIKV alphaviruses were cross-reactive to E2EP3. Interestingly, some of these antibodies demonstrated clearly in vitro CHIKV neutralizing activity. Contrastingly, serum samples from flaviviruses-infected patients showed a low level of cross-reactivity against E2EP3. Using CHIKV E2EP3 as a serology marker not only allows early detection of CHIKV specific antibodies, but would also allow the differentiation between CHIKV infections and flavivirus infections with 93% accuracy, thereby allowing precise acute febrile diagnosis and improving clinical management in regions newly suffering from CHIKV outbreaks including the Americas.

  11. Molecular genome tracking of East, Central and South African genotype of Chikungunya virus in South-east Asia between 2006 and 2009

    Institute of Scientific and Technical Information of China (English)

    Kamol Suwannakarn; Apiradee Theamboonlers; Yong Poovorawan

    2011-01-01

    Objective:To understand the epidemiology of the East, Central and South African(ECSA) genotype of Chikungunya virus(CHIKV)in terms of emerging and re-emerging infections, this study has been aimed at investigating the evolutionary parameters, genomic signatures and molecular tracking of theCHIKV ECSA genotype in South-east Asia and coastal areas of the Indian Ocean between 2006 and 2009 by using phylogenetic analysis and the Bayesian Markov Chain Monte Carlo (BMCMC) evolutionary estimation.Methods: Nearly complete genome sequences of53 CHIKV isolates from all genotypes were subjected to phylogenetic analysis and evolutionary parameter estimation. The amino acids of67of ECSA genotype during2006 to2009 were compared for finding molecular signature tracking. The ECSA genotype signatures were visualized to find the possible transmission root was projected onto a geographic map.Results:Phylogenetic analysis showed theECSA genotype was divided into2 groups. The first group comprises viruses from India and Southeast Asian countries. The second group consists of strains typically circulating in Sri Lanka in2008. The evolutionary parameters of these groups depicted the time of the most recent common ancestor at approximately 7.5years ago. The genomic signatures revealed the positions of amino acid variation in each group.Conclusions:The molecular evolution projected onto a geographical map showed the routes ofCHIKVtransmission from 2006 to2009. Molecular tracking will assist in understanding transmission routes, epidemiology and molecular evolution ofCHIKV.

  12. Connective tissue metabolism in chikungunya patients

    Directory of Open Access Journals (Sweden)

    Vemula Sarojamma

    2008-02-01

    Full Text Available Abstract Background Chikungunya (CHIK fever is a viral disease transmitted to humans by the bite of Chikungunya virus (CHIK virus infected Aedes mosquitoes. CHIK virus is a member of the Alphavirus genus of the family Togaviridae. Previous reports have indicated that infection with CHIK virus produces an acute arthritis in human hosts by large area of necrosis and collagenosis or fibrosis. Results We carried out the present study to determine the effect of chikungunya on the collagen and connective tissue metabolism in 75 chikungunya-affected people. First, we screened for mucopolysaccharides in urine by Cetyl Trimethyl Ammonium Bromide (CTAB test. Appearance of heavy precipitate indicates the presence of higher levels of mucopolysaccharides and later quantified by DMB dye method. The urinary mucopolysaccharide in CHIK patients was 342 ± 45 mg/l compared to healthy controls (45 ± 5.6 mg/l. The collagen building blocks, proline and hydroxyproline were also measured in CHIK patients and observed higher excretion compared to healthy controls. Urinary excretions hydroxyproline was greater than the proline levels. Conclusion These results indicate that CHIK virus infection affects and damage the cartilage and connective metabolism and releases the degraded products from the tissue and responsible for increasing the levels of proline, hydroxyproline and mucopolysaccharides in CHIK affected patients.

  13. Molecular Characterisation of Chikungunya Virus Infections in Trinidad and Comparison of Clinical and Laboratory Features with Dengue and Other Acute Febrile Cases.

    Science.gov (United States)

    Sahadeo, Nikita; Mohammed, Hamish; Allicock, Orchid M; Auguste, Albert J; Widen, Steven G; Badal, Kimberly; Pulchan, Krishna; Foster, Jerome E; Weaver, Scott C; Carrington, Christine V F

    2015-11-01

    Local transmission of Chikungunya virus (CHIKV) was first documented in Trinidad and Tobago (T&T) in July 2014 preceding a large epidemic. At initial presentation, it is difficult to distinguish chikungunya fever (CHIKF) from other acute undifferentiated febrile illnesses (AUFIs), including life-threatening dengue disease. We characterised and compared dengue virus (DENV) and CHIKV infections in 158 patients presenting with suspected dengue fever (DF) and CHIKF at a major hospital in T&T, and performed phylogenetic analyses on CHIKV genomic sequences recovered from 8 individuals. The characteristics of patients with and without PCR-confirmed CHIKV were compared using Pearson's χ2 and student's t-tests, and adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were determined using logistic regression. We then compared signs and symptoms of people with RT-qPCR-confirmed CHIKV and DENV infections using the Mann-Whitney U, Pearson's χ2 and Fisher's exact tests. Among the 158 persons there were 8 (6%) RT-qPCR-confirmed DENV and 30 (22%) RT-qPCR-confirmed CHIKV infections. Phylogenetic analyses showed that the CHIKV strains belonged to the Asian genotype and were most closely related to a British Virgin Islands strain isolated at the beginning of the 2013/14 outbreak in the Americas. Compared to persons who were RT-qPCR-negative for CHIKV, RT-qPCR-positive individuals were significantly more likely to have joint pain (aOR: 4.52 [95% CI: 1.28-16.00]), less likely to be interviewed at a later stage of illness (days post onset of fever--aOR: 0.56 [0.40-0.78]) and had a lower white blood cell count (aOR: 0.83 [0.71-0.96]). Among the 38 patients with RT-qPCR-confirmed CHIKV or DENV, there were no significant differences in symptomatic presentation. However when individuals with serological evidence of recent DENV or CHIKV infection were included in the analyses, there were key differences in clinical presentation between CHIKF and other AUFIs including DF, which

  14. Construction of Pseudovirus Based on Chikungunya Virus Envelope Protein%基孔肯雅病毒囊膜蛋白假病毒模型的构建

    Institute of Scientific and Technical Information of China (English)

    王晓娜; 安小平; 范华昊; 王娟; 李建彬; 刘大斌; 姜焕焕; 米志强; 童贻刚

    2011-01-01

    目的:以HIV为骨架构建单次复制性的含基孔肯雅病毒囊膜蛋白的假病毒模型,观察其对哺乳动物细胞的侵染性.方法:PCR合成基孔肯雅病毒囊膜蛋白基因,克隆到真核表达载体上,与HIV慢病毒包装系统质粒共转染293FT细胞,48 h后收培养上清,在8μg/mL Polybrene存在下感染293FT细胞,感染48 h后在荧光显微镜下观察结果.结果:PCR合成了基孔肯雅病毒囊膜蛋白基因并克隆到真核表达载体上,测序结果正确;共转染293FT细胞后,检测到基孔肯雅病毒囊膜蛋白的表达并包装成假病毒,感染新鲜293FT细胞后能够检测到绿色荧光蛋白.结论:合成的基孔肯雅病毒囊膜蛋白基因能正确表达并包装成假病毒,含基孔肯雅病毒囊膜蛋白的假病毒能感染293FT细胞并表达绿色荧光蛋白,可用该假病毒模型进一步研究基孔肯雅病毒的感染性,筛选评价抗基孔肯雅病毒药物.%Objective: To construct replication-defective HIV-backborn pseudovirus using Chikungunya virus envelope protein and observe its infection in mammalian cells. Methods: The sequence of Chikungunya virus envelope protein gene was synthesized using overlapping PCR method and then was cloned into eukaryotic vector. The above plasmid was co-transfected into 293FT cells with HIV-based lentivirus packaging plasmids. Supernatant was collected and filtered with 0.22 μm filter after 48 hours, then was used to infect fresh 293FT cells in the presence of 8 μg/mL Polybrene. Results: The results of sequencing showed that correct sequence of Chikungunya virus envelope protein gene was synthesized and cloned into eukaryotic vector. The expression of Chikungunya virus envelope protein was observed and packaged into pseudovirus which could infect fresh 293FT cells effectively. Conclusion: The synthesized envelope protein gene of Chikungunya virus can be expressed correctly and packaged into pseudovirus. The packaged pseudovirus can infect 293FT

  15. Chikungunya in Europe: What’s next?

    Science.gov (United States)

    In August 2004, Kenyan health authorities and partners identified chikungunya virus as the cause of a febrile epidemic in humans in a coastal island city. This epidemic spread to Indian Ocean islands and India, where it continues and more than 1 million cases are suspected. Rezza and colleagues des...

  16. Analysis of imported chikungunya fever cases detected at frontier ports of Guangdong Entry-Exit Inspection and Quarantine Bureau%广东出入境检验检疫局口岸输入性基孔肯雅热监测分析

    Institute of Scientific and Technical Information of China (English)

    黄鹂; 张显光; 张文; 邓荆; 林少佳; 吴惠明; 黄吉城; 戴俊; 潘德观

    2013-01-01

    目的 分析广东出入境检验检疫局口岸检出的输入性基孔肯雅热病例的监测情况,为输入性传染病防控工作提供参考依据.方法 以广东出入境检验检疫局口岸2008-2011年入境人员作为调查对象,对来自基孔肯雅热流行区的发热人员进行流行病学个案调查,判定染疫嫌疑的采集样本送检,对阳性病例资料和检出情况进行分析.结果 11例病例均来自基孔肯雅热流行区;均为输入性病例,其中9例入境时在发病,2例入境后医学观察期间发病;平均年龄40.2岁,以男性中青年为主;体温监测是主要检出手段;未发生二代病例.结论 广东出入境检验检疫局口岸防制基孔肯雅热的措施适当得力,能有效阻止基孔肯雅病毒通过口岸进行传播.%Objective To analyze the imported chikungunya fever cases detected at the frontier ports of Guangdong Entry-Exit Inspection and Quarantine Bureau and to provide a basis for control of imported infectious diseases.Methods Surveillance was conducted in the entry passengers at the frontier ports of Guangdong Entry-Exit Inspection and Quarantine Bureau from 2008 to 2011,and epidemiological investigation was carried out in the feverish passengers from the epidemic area of chikungunya fever.The blood samples of suspected cases were collected for laboratory test,and the information of positive cases were analyzed.Results Eleven cases of chikungunya fever,all from the epidemic area of chikungunya fever,were detected; of these imported cases,9 were in the period of disease while passing the frontier ports,and the other 2 were in incubation period and had an onset in the observation period after entry.The mean age of the 11 cases was 40.2 years; most of them were young and middle-aged males.The primary detection method was fever surveillance.There were no secondary cases.Conclusion Control measures against chikungunya fever are properly taken by Guangdong Entry-Exit Inspection and

  17. Chikungunya: an overview

    Indian Academy of Sciences (India)

    A B Sudeep; D Parashar

    2008-11-01

    Chikungunya (CHIK), a mosquito borne debilitating disease, is caused by CHIK virus, an alphavirus belonging to the family Togaviridae. The sudden onset of very high fever along with rash, and severe arthralgia especially in the small joints of hands and toes are the characteristics of the disease. It was first reported from Tanzania in 1952-53 and spread subsequently to sub-Saharan Africa, South East Asia and Pacific causing large epidemics. The virus exists in three genotypes, the Asian, West African and East Central South African that are responsible for outbreaks in the respective areas. The first outbreak in Asia was in Bangkok in 1958 followed by other Asian countries. India experienced massive outbreaks of CHIK in the 1960s and early 70s mainly in cities. After a gap of 32 years an explosive outbreak of CHIK devastated the country affecting more than 1.4 million people in 13 states. The epidemic also witnessed many unusual clinico-pathological complications including CHIK associated deaths and mother to child transmission. High morbidity with severe arthralgia persisted for several months made the people mentally and physically weak. This review describes CHIK in general and highlights the various clinico-pathological aspects observed during the recent outbreak.

  18. Vector competence of Aedes aegypti and Aedes vittatus (Diptera: Culicidae) from Senegal and Cape Verde archipelago for West African lineages of chikungunya virus.

    Science.gov (United States)

    Diagne, Cheikh T; Faye, Oumar; Guerbois, Mathilde; Knight, Rachel; Diallo, Diawo; Faye, Ousmane; Ba, Yamar; Dia, Ibrahima; Faye, Ousmane; Weaver, Scott C; Sall, Amadou A; Diallo, Mawlouth

    2014-09-01

    To assess the risk of emergence of chikungunya virus (CHIKV) in West Africa, vector competence of wild-type, urban, and non-urban Aedes aegypti and Ae. vittatus from Senegal and Cape Verde for CHIKV was investigated. Mosquitoes were fed orally with CHIKV isolates from mosquitoes (ArD30237), bats (CS13-288), and humans (HD180738). After 5, 10, and 15 days of incubation following an infectious blood meal, presence of CHIKV RNA was determined in bodies, legs/wings, and saliva using real-time reverse transcription-polymerase chain reaction. Aedes vittatus showed high susceptibility (50-100%) and early dissemination and transmission of all CHIKV strains tested. Aedes aegypti exhibited infection rates ranging from 0% to 50%. Aedes aegypti from Cape Verde and Kedougou, but not those from Dakar, showed the potential to transmit CHIKV in saliva. Analysis of biology and competence showed relatively high infective survival rates for Ae. vittatus and Ae. aegypti from Cape Verde, suggesting their efficient vector capacity in West Africa. PMID:25002293

  19. Failure to demonstrate experimental vertical transmission of the epidemic strain of Chikungunya virus in Aedes albopictus from La Réunion Island, Indian Ocean

    Directory of Open Access Journals (Sweden)

    Marie Vazeille

    2009-07-01

    Full Text Available Aedes albopictus was responsible for transmission in the first outbreak of chikungunya (CHIK on La Réunion Island, Indian Ocean, in 2005-2006. The magnitude of the outbreak on this island, which had been free of arboviral diseases for over 30 years, as well as the efficiency of Ae. albopictus as the main vector, raises questions about the maintenance of the CHIK virus (CHIKV through vertical transmission mechanisms. Few specimens collected from the field as larvae were found to be infected. In this study, Ae. albopictus originating from La Réunion were orally infected with a blood-meal containing 10(8 pfu/mL of the CHIKV epidemic strain (CHIKV 06.21. Eggs from the first and second gonotrophic cycles were collected and raised to the adult stage. The infectious status of the progeny was checked (i by immunofluorescence on head squashes of individual mosquitoes to detect the presence of viral particles or (ii by quantitative RT-PCR on mosquito pools to detect viral RNA. We analysed a total of 1,675 specimens from the first gonotrophic cycle and 1,709 from the second gonotrophic cycle without detecting any viral particles or viral RNA. These laboratory results are compared to field records.

  20. High rate of subclinical chikungunya virus infection and association of neutralizing antibody with protection in a prospective cohort in the Philippines.

    Directory of Open Access Journals (Sweden)

    In-Kyu Yoon

    2015-05-01

    Full Text Available Chikungunya virus (CHIKV is a globally re-emerging arbovirus for which previous studies have indicated the majority of infections result in symptomatic febrile illness. We sought to characterize the proportion of subclinical and symptomatic CHIKV infections in a prospective cohort study in a country with known CHIKV circulation.A prospective longitudinal cohort of subjects ≥6 months old underwent community-based active surveillance for acute febrile illness in Cebu City, Philippines from 2012-13. Subjects with fever history were clinically evaluated at acute, 2, 5, and 8 day visits, and at a 3-week convalescent visit. Blood was collected at the acute and 3-week convalescent visits. Symptomatic CHIKV infections were identified by positive CHIKV PCR in acute blood samples and/or CHIKV IgM/IgG ELISA seroconversion in paired acute/convalescent samples. Enrollment and 12-month blood samples underwent plaque reduction neutralization test (PRNT using CHIKV attenuated strain 181/clone25. Subclinical CHIKV infections were identified by ≥8-fold rise from a baseline enrollment PRNT titer 50 years old. Baseline CHIKV PRNT titer ≥10 was associated with 100% (95%CI: 46.1, 100.0 protection from symptomatic CHIKV infection. Phylogenetic analysis demonstrated Asian genotype closely related to strains from Asia and the Caribbean.Subclinical infections accounted for a majority of total CHIKV infections. A positive baseline CHIKV PRNT titer was associated with protection from symptomatic CHIKV infection. These findings have implications for assessing disease burden, understanding virus transmission, and supporting vaccine development.

  1. Development of 2, 7-Diamino-1, 8-Naphthyridine (DANP) Anchored Hairpin Primers for RT-PCR Detection of Chikungunya Virus Infection

    Science.gov (United States)

    Chen, Huixin; Parimelalagan, Mariya; Takei, Fumie; Hapuarachchi, Hapuarachchige Chanditha; Koay, Evelyn Siew-Chuan; Ng, Lee Ching; Ho, Phui San; Nakatani, Kazuhiko; Chu, Justin Jang Hann

    2016-01-01

    A molecular diagnostic platform with DANP-anchored hairpin primer was developed and evaluated for the rapid and cost-effective detection of Chikungunya virus (CHIKV) with high sensitivity and specificity. The molecule 2, 7-diamino-1, 8-naphthyridine (DANP) binds to a cytosine-bulge and emits fluorescence at 450 nm when it is excited by 400 nm light. Thus, by measuring the decline in fluorescence emitted from DANP—primer complexes after PCR reaction, we could monitor the PCR progress. By adapting this property of DANP, we have previously developed the first generation DANP-coupled hairpin RT-PCR assay. In the current study, we improved the assay performance by conjugating the DANP molecule covalently onto the hairpin primer to fix the DANP/primer ratio at 1:1; and adjusting the excitation emission wavelength to 365/430 nm to minimize the background signal and a ‘turn-on’ system is achieved. After optimizing the PCR cycle number to 30, we not only shortened the total assay turnaround time to 60 minutes, but also further reduced the background fluorescence. The detection limit of our assay was 0.001 PFU per reaction. The DANP-anchored hairpin primer, targeting nsP2 gene of CHIKV genome, is highly specific to CHIKV, having no cross-reactivity to a panel of other RNA viruses tested. In conclusion, we report here a molecular diagnostic assay that is sensitive, specific, rapid and cost effective for CHIKV detection and can be performed where no real time PCR instrumentation is required. Our results from patient samples indicated 93.62% sensitivity and 100% specificity of this method, ensuring that it can be a useful tool for rapid detection of CHIKV for outbreaks in many parts of the world. PMID:27571201

  2. Development of novel antibodies against non-structural proteins nsP1, nsP3 and nsP4 of chikungunya virus: potential use in basic research.

    Science.gov (United States)

    Kumar, Sameer; Mamidi, Prabhudutta; Kumar, Abhishek; Basantray, Itishree; Bramha, Umarani; Dixit, Anshuman; Maiti, Prasanta Kumar; Singh, Sujay; Suryawanshi, Amol Ratnakar; Chattopadhyay, Subhasis; Chattopadhyay, Soma

    2015-11-01

    Chikungunya virus (CHIKV) has reemerged recently as an important pathogen, causing several large epidemics worldwide. This necessitates the development of better reagents to understand its biology and to establish effective and safe control measures. The present study describes the development and characterization of polyclonal antibodies (pAbs) against synthetic peptides of CHIKV non-structural proteins (nsPs; nsP1, nsP3 and nsP4). The reactivity of these pAbs was demonstrated by ELISA and Western blot. Additionally, in vitro infection studies in a mammalian system confirmed that these pAbs are highly sensitive and specific for CHIKV nsPs, as these proteins were detected very early during viral replication. Homology analysis of the selected epitope sequences revealed that they are conserved among all of the CHIKV strains of different genotypes, while comparison with other alphavirus sequences showed that none of them are 100% identical to the epitope sequences (except Onyong-nyong and Igbo Ora viruses, which show 100% identity to the nsP4 epitope). Interestingly, two different forms of CHIKV nsP1 and three different forms of nsP3 were detected in Western blot analysis during infection; however, further experimental investigations are required to confirm their identity. Also, the use of these antibodies demonstrated faster and enhanced expression profiles of all CHIKV nsPs in 2006 Indian outbreak strains when compared to the CHIKV prototype strain, suggesting the epidemic potential of the 2006 isolate. Accordingly, it can be suggested that the pAbs reported in this study can be used as sensitive and specific tools for experimental investigations of CHIKV replication and infection.

  3. Development of novel antibodies against non-structural proteins nsP1, nsP3 and nsP4 of chikungunya virus: potential use in basic research.

    Science.gov (United States)

    Kumar, Sameer; Mamidi, Prabhudutta; Kumar, Abhishek; Basantray, Itishree; Bramha, Umarani; Dixit, Anshuman; Maiti, Prasanta Kumar; Singh, Sujay; Suryawanshi, Amol Ratnakar; Chattopadhyay, Subhasis; Chattopadhyay, Soma

    2015-11-01

    Chikungunya virus (CHIKV) has reemerged recently as an important pathogen, causing several large epidemics worldwide. This necessitates the development of better reagents to understand its biology and to establish effective and safe control measures. The present study describes the development and characterization of polyclonal antibodies (pAbs) against synthetic peptides of CHIKV non-structural proteins (nsPs; nsP1, nsP3 and nsP4). The reactivity of these pAbs was demonstrated by ELISA and Western blot. Additionally, in vitro infection studies in a mammalian system confirmed that these pAbs are highly sensitive and specific for CHIKV nsPs, as these proteins were detected very early during viral replication. Homology analysis of the selected epitope sequences revealed that they are conserved among all of the CHIKV strains of different genotypes, while comparison with other alphavirus sequences showed that none of them are 100% identical to the epitope sequences (except Onyong-nyong and Igbo Ora viruses, which show 100% identity to the nsP4 epitope). Interestingly, two different forms of CHIKV nsP1 and three different forms of nsP3 were detected in Western blot analysis during infection; however, further experimental investigations are required to confirm their identity. Also, the use of these antibodies demonstrated faster and enhanced expression profiles of all CHIKV nsPs in 2006 Indian outbreak strains when compared to the CHIKV prototype strain, suggesting the epidemic potential of the 2006 isolate. Accordingly, it can be suggested that the pAbs reported in this study can be used as sensitive and specific tools for experimental investigations of CHIKV replication and infection. PMID:26280524

  4. Mosquito vector indicators and virus detection during Chikungunya fever outbreak in Dongguan,Guangdong province%一起基孔肯雅热暴发的蚊媒监控及其病毒检测

    Institute of Scientific and Technical Information of China (English)

    段金花; 蔡松武; 吴德; 刘文华; 吴军; 周惠琼; 邹钦

    2012-01-01

    目的 分析基孔肯雅热流行与诱蚊诱卵指数的关系,调查白纹伊蚊成幼虫感染基孔肯雅病毒状况.方法 基孔肯雅热流行期间,通过诱蚊诱卵器和布雷图指数调查蚊虫密度和采集蚊虫,用实时荧光PCR和细胞分离2种方法对野外捕获的白纹伊蚊体内病毒进行检测.结果 确认基孔肯雅热暴发流行后,启动包括应急灭蚊的综合控制措施1周后,疫情得到有效控制,布雷图指数和诱蚊诱卵指数下降到5以下;采集的蚊样品按照时间和地点分成27份进行病毒检测,成蚊标本都显示病毒阴性,有3份乙醇浸泡处理的蚊幼虫标本为可疑阳性,占总幼虫标本(24份)的12.5%.细胞培养分离病毒均为阴性.该社区共报告病例253例,应急控制在22d结束.结论 基孔肯雅热暴发流行时,诱蚊诱卵器法作为应急灭蚊安全、有效、简便易行的评价方法,尤其在成蚊控制效果评价和捕获成蚊检测带病毒指数上有优势,流行期间白纹伊蚊对基孔肯雅病毒的感染率、传播率有待进一步研究.%Objective To analyze the association between prevalence of Chikungunya fever and Mosq-ovitrap index (MOI) and to investigate the infection with Chikungunya virus (CHIKV) in larval and adult Aedes albopictus. Methods Mosquitoes were collected by mosq-ovitrap and the mosquito density was also determined by Breteau index (BI) during Chikungunya fever outbreak. CHIKV was detected in the Ae. Albopictus samples collected in the field by real-time fluorescence PCR and cell culture for isolation. Results Comprehensive emergency control measures were taken for anti-mosquito purpose after the confirmation of Chikungunya fever outbreak. After one week of emergency management, the epidemic situation was effectively controlled, as shown by the fact that both MOI and BI were lower than 5. The collected mosquito samples were divided into 27 groups according to collection time and location, and then CHIKV

  5. First Imported Case of Zika Virus Infection into Korea

    OpenAIRE

    Jang, Hee-Chang; Park, Wan Beom; Kim, Uh Jin; Chun, June Young; Choi, Su-jin; Choe, Pyoeng Gyun; Jung, Sook-In; Jee, Youngmee; Kim, Nam Joong; Choi, Eun Hwa; Oh, Myoung-Don

    2016-01-01

    Since Zika virus has been spreading rapidly in the Americas from 2015, the outbreak of Zika virus infection becomes a global health emergency because it can cause neurological complications and adverse fetal outcome including microcephaly. Here, we report clinical manifestations and virus isolation findings from a case of Zika virus infection imported from Brazil. The patient, 43-year-old Korean man, developed fever, myalgia, eyeball pain, and maculopapular rash, but not neurological manifest...

  6. 应用含内参的多重实时荧光RT-PCR方法快速检测登革病毒和基孔肯雅病毒%Rapid detection of Dengue virus and Chikungunya virus by multiplex real-time RT-PCR assay with an internal control

    Institute of Scientific and Technical Information of China (English)

    郑夔; 丁国允; 周惠琼; 谢雪妹; 李小波; 师永霞; 苏锦坤; 黄吉城

    2013-01-01

    目的 建立一种登革病毒、基孔肯雅病毒并含人类基因内参检测的多重实时荧光RT-PCR方法,能在同一反应管内同时检测目前发现的所有来源的登革病毒或基孔肯雅病毒.方法 针对登革病毒3′端非编码区和基孔肯雅病毒结构蛋白E2-6K-E1区以及人体各类组织细胞中均能稳定表达的RNAse P基因,设计了3套特异性引物和探针,建立了1套能同时检测登革病毒、基孔肯雅病毒及含有人类基因检测内参的多重实时荧光RT-PCR方法,对其灵敏性和特异性进行了验证,并对临床发热病人标本进行了应用评估.结果 该方法对检测体外转录合成的登革病毒和基孔肯雅病毒RNA的灵敏性可达最低每个反应10~100拷贝,对检测登革1型病毒和基孔肯雅病毒的灵敏性分别可达最低每个反应0.1 TCID50/mL和1 TCID50/mL.用20株登革病毒、4株基孔肯雅病毒和日本脑炎病毒、西尼罗病毒、黄热病毒、盖塔病毒、辛德毕斯病毒各1株进行检测,方法的特异性均为100%.方法应用于189份发热病人血清标本检测,可准确地鉴定出其中登革病毒或基孔肯雅病毒核酸阳性的标本,且所有血清标本均能被内参引物和探针有效地扩增和杂交.结论 本研究建立了一种高灵敏性、高特异性且含人类基因内参检测的登革病毒和基孔肯雅病毒多重实时荧光RT-PCR检测方法,可作为登革热或基孔肯雅热病人早期快速鉴别诊断的有效工具,也可用于蚊媒携带登革病毒或基孔肯雅病毒的高通量快速筛查.%The purpose was to establish a multiplex real-time RT-PCR assay for detection of Dengue virus and Chikun-gunya virus in one tube, which could detect all Dengue virus or Chikungunya virus strains from different origins . Based on sequences of 3 -UTR of Dengue virus , E2-6K-E1 region of Chikungunya virus's structural protein and RNAse P gene which stably expressed in all human organs , 3 pairs of

  7. 实时荧光PCR检测基孔肯雅病毒方法的建立及初步应用%The Establishment of Real Time Fluorescent PCR Detecting Method and Preliminary Application on Pathogenesis of Chikungunya Virus

    Institute of Scientific and Technical Information of China (English)

    方巧云; 琚雄飞; 刘特; 严宇斌; 刘燕; 曾健君

    2012-01-01

    Objective To establish real time PCR (RT -PCR) detection method for Chikungunya virus. Methods Primer and FAM probe were chosen for virus gene. The samples were analyzed by TaqMan - FAM PCR and SYBR Green - based RT - PCR techniques on a fluorescence real - time PCR instrument, and the results were compared with those by conventional RT - PCR. Results TaqMan PCR and SYBR RT - PCR positive rates of Chikungunya virus were 17. 5% and 17. 5% ; the conventional RT - PCR were 15%. These results revealed much rapid and increase sensitivity of the real - time PCR method. There were no significant differences between these methods. Conclusion The fluorescence quantitative PCR provides a more specific, more rapid and sensitive method for quantitative detection of Chikungunya virus. It is helpful for the rapid detection of Chikungunya fever.%目的 建立基孔肯雅病毒的荧光定量PCR检测方法.方法 针对基孔肯雅病毒的基因序列,设计、合成引物、探针及反应体系,摸索出最佳反应条件,建立TaqMan荧光探针法和SYBR荧光染料法.利用建立的方法对30例基孔肯雅热病标本和10份基孔肯雅病毒保存液进行扩增、检测和结果分析,并与常规RT - PCR方法的检测结果进行比对.结果 实时荧光定量PCR法比常规RT - PCR法快速、灵敏.40份标本TaqMan荧光探针法、SYBR荧光染料法和常规RT - PCR方法的阳性率分别为:17.5%、17.5%、15%.统计分析表明,3种方法差异不具有统计学意义.结论 实时荧光定量PCR方法快速且具有较好的特异性、敏感性、重复性,适用于基孔肯雅病毒的快速检验.

  8. First Imported Case of Zika Virus Infection into Korea.

    Science.gov (United States)

    Jang, Hee-Chang; Park, Wan Beom; Kim, Uh Jin; Chun, June Young; Choi, Su-Jin; Choe, Pyoeng Gyun; Jung, Sook-In; Jee, Youngmee; Kim, Nam-Joong; Choi, Eun Hwa; Oh, Myoung-Don

    2016-07-01

    Since Zika virus has been spreading rapidly in the Americas from 2015, the outbreak of Zika virus infection becomes a global health emergency because it can cause neurological complications and adverse fetal outcome including microcephaly. Here, we report clinical manifestations and virus isolation findings from a case of Zika virus infection imported from Brazil. The patient, 43-year-old Korean man, developed fever, myalgia, eyeball pain, and maculopapular rash, but not neurological manifestations. Zika virus was isolated from his semen, and reverse-transcriptase PCR was positive for the virus in the blood, urine, and saliva on the 7th day of the illness but was negative on the 21st day. He recovered spontaneously without any neurological complications. He is the first case of Zika virus infection in Korea imported from Brazil.

  9. First Imported Case of Zika Virus Infection into Korea

    Science.gov (United States)

    Jee, Youngmee

    2016-01-01

    Since Zika virus has been spreading rapidly in the Americas from 2015, the outbreak of Zika virus infection becomes a global health emergency because it can cause neurological complications and adverse fetal outcome including microcephaly. Here, we report clinical manifestations and virus isolation findings from a case of Zika virus infection imported from Brazil. The patient, 43-year-old Korean man, developed fever, myalgia, eyeball pain, and maculopapular rash, but not neurological manifestations. Zika virus was isolated from his semen, and reverse-transcriptase PCR was positive for the virus in the blood, urine, and saliva on the 7th day of the illness but was negative on the 21st day. He recovered spontaneously without any neurological complications. He is the first case of Zika virus infection in Korea imported from Brazil. PMID:27366020

  10. Novel Lesions of Bones and Joints Associated with Chikungunya Virus Infection in Two Mouse Models of Disease: New Insights into Disease Pathogenesis.

    Directory of Open Access Journals (Sweden)

    Brad A Goupil

    Full Text Available Chikungunya virus is an arbovirus spread predominantly by Aedes aegypti and Ae. albopictus mosquitoes, and causes debilitating arthralgia and arthritis. While these are common manifestations during acute infection and it has been suggested they can recur in patients chronically, gaps in knowledge regarding the pathogenesis still exist. Two established mouse models were utilized (adult IRF 3/7 -/- -/- and wild-type C57BL/6J mice to evaluate disease manifestations in bones and joints at various timepoints. Novel lesions in C57BL/6J mice consisted of periostitis (91% and foci of cartilage of necrosis (50% of mice at 21 DPI. Additionally, at 21 DPI, 50% and 75% of mice exhibited periosteal bone proliferation affecting the metatarsal bones, apparent via histology and μCT, respectively. μCT analysis did not reveal any alterations in trabecular bone volume measurements in C57BL/6J mice. Novel lesions demonstrated in IRF 3/7 -/- -/- mice at 5 DPI included focal regions of cartilage necrosis (20%, periosteal necrosis (66%, and multifocal ischemic bone marrow necrosis (100%. Contralateral feet in 100% of mice of both strains had similar, though milder lesions. Additionally, comparison of control IRF 3/7 -/- -/- and wild-type C57BL/6J mice demonstrated differences in cortical bone. These experiments demonstrate novel manifestations of disease similar to those occurring in humans, adding insight into disease pathogenesis, and representing new potential targets for therapeutic interventions. Additionally, results demonstrate the utility of μCT in studies of bone and joint pathology and illustrate differences in bone dynamics between mouse strains.

  11. Effectiveness of ultra-low volume nighttime applications of an adulticide against diurnal Aedes albopictus, a critical vector of dengue and chikungunya viruses.

    Directory of Open Access Journals (Sweden)

    Ary Farajollahi

    Full Text Available Aedes albopictus, the Asian tiger mosquito, continues expanding its geographic range and involvement in mosquito-borne diseases such as chikungunya and dengue. Vector control programs rarely attempt to suppress this diurnal species with an ultra-low volume (ULV adulticide because for maximum efficacy applications are conducted at night. During 2009-2011 we performed experimental nighttime applications of a novel adulticide (DUET® against field populations of Ae. albopictus within an urban site composed of approximately 1,000 parcels (home and yard in northeastern USA. Dual applications at mid label rate of the adulticide spaced one or two days apart accomplished significantly higher control (85.0 ± 5.4% average reduction than single full rate applications (73.0 ± 5.4%. Our results demonstrate that nighttime ULV adulticiding is effective in reducing Ae. albopictus abundance and highlight its potential for use as part of integrated pest management programs and during disease epidemics when reducing human illness is of paramount importance.

  12. Presence and Distribution of Economically Important Potato Viruses in Montenegro

    Directory of Open Access Journals (Sweden)

    Jelena Zindović

    2011-01-01

    Full Text Available The research was carried out, in the period 2002-2004 in order to determine the presence and distribution of potato viruses at 12 different locations and on 9 different potato varieties grown in Montenegro. The research included collecting of samples in seed potato crops and testing of six economically important potato viruses: Potato leaf roll virus (PLRV, Potato virus Y (PVY, Potato virus X (PVX, Potato virus S (PVS, Potato virus A (PVA i Potato virus M (PVM. Using the direct enzyme-linked immunosorbent assay (DAS-ELISA and commercial antisera specific for six potato viruses, it was found that PVY was the most frequent virus during the three-year research period. The second frequent virus was PVS, followed by PVA, PLRV, PVM and PVX. Single and mixed infections were detected, and the most prevalent were the single infections of PVY. Also, in the period 2002-2004, PVY had the highest distribution and the number of present viruses was different at different localities and on different potato varieties. Further investigations were related to detailed characterization of the most prevalent virus (PVY, which is at the same time economically the most important one. Serological characterization of PVY was performed utilizing DAS-ELISA kit with commercial monoclonal antibodies specific for detection of the three strain groups of PVY, and the two straingroups - necrotic (PVYN/PVYNTN and common (PVYO, were identified. Necrotic strains were prevalent in 2002 and 2004, while in 2003 PVYO was the most frequent strain in virus population. The presence of stipple streak strain (PVYC was not detected in any of the testedsamples.

  13. Zika virus infections imported from Brazil to Portugal, 2015

    Directory of Open Access Journals (Sweden)

    L. Zé-Zé

    2016-01-01

    Here, we present the clinical and laboratory aspects related to the first four imported human cases of Zika virus in Portugal from Brazil, and alert, regarding the high level of traveling between Portugal and Brazil, and the ongoing expansion of this virus in the Americas, for the threat for Zika virus introduction in Europe and the possible introduction to Madeira Island where Aedes aegypti is present.

  14. [Chikungunya on Reunion Island: chronicle of an epidemic foretold].

    Science.gov (United States)

    Paganin, Fabrice; Borgherini, Giannandrea; Staikowsky, Frédéric; Arvin-Berod, Claude; Poubeau, Patrice

    2006-04-01

    Chikungunya is a viral disease transmitted by a mosquito of the genus Aedes. It is currently epidemic on Reunion Island, in the Indian Ocean. It is essentially characterized by an influenza syndrome but associated with polyarthralgia and an eruption. The disabling and chronic nature of the arthralgia is the most remarkable clinical aspect of chikungunya infection. Severe and unusual forms have appeared, not previously described in the literature. These forms must be studied to determine whether there is a direct relation between the chikungunya virus and the severity factors. Treatment is solely symptomatic, combining analgesic and/or antiinflammatory agents. There is no vaccine. The epidemic is not limited to Reunion: cases of chikungunya have also been reported in neighboring islands (Maurice, Seychelles, and Madagascar). Travelers planning to visit the region should be counseled. PMID:16614609

  15. Chikungunya viral disease in district Bhilwara (Rajasthan) India.

    Science.gov (United States)

    Jain, S K; Kumar, Kaushal; Bhattacharya, D; Venkatesh, S; Jain, D C; Lal, Shiv

    2007-03-01

    An investigation of chikungunya outbreak cases was carried out in Bhilwara District, Rajasthan during Aug-Sep 2006. Fever with multiple joint pains was the first presenting feature. Aedes larval surveys indicate high Breteau index (78.6 to 200), House index (48.0 to 83.3) & Container index (41.1 to 73.6) above the critical index. Out of 40 sera samples tested, 12 showed HI antibodies for chikungunya virus in high titres and another five were positive for IgM antibodies against chikungunya. The clinico-epidemiological, laboratory and entomological investigations confirm that this episode of fever was due to chikungunya fever. Strengthening and intensification of surveillance along with educating the community were recommended for control of outbreak. PMID:18338713

  16. Chikungunya Virus–Vector Interactions

    Directory of Open Access Journals (Sweden)

    Lark L. Coffey

    2014-11-01

    Full Text Available Chikungunya virus (CHIKV is a mosquito-borne alphavirus that causes chikungunya fever, a severe, debilitating disease that often produces chronic arthralgia. Since 2004, CHIKV has emerged in Africa, Indian Ocean islands, Asia, Europe, and the Americas, causing millions of human infections. Central to understanding CHIKV emergence is knowledge of the natural ecology of transmission and vector infection dynamics. This review presents current understanding of CHIKV infection dynamics in mosquito vectors and its relationship to human disease emergence. The following topics are reviewed: CHIKV infection and vector life history traits including transmission cycles, genetic origins, distribution, emergence and spread, dispersal, vector competence, vector immunity and microbial interactions, and co-infection by CHIKV and other arboviruses. The genetics of vector susceptibility and host range changes, population heterogeneity and selection for the fittest viral genomes, dual host cycling and its impact on CHIKV adaptation, viral bottlenecks and intrahost diversity, and adaptive constraints on CHIKV evolution are also discussed. The potential for CHIKV re-emergence and expansion into new areas and prospects for prevention via vector control are also briefly reviewed.

  17. Neurocognitive outcome of children exposed to perinatal mother-to-child Chikungunya virus infection: the CHIMERE cohort study on Reunion Island.

    Directory of Open Access Journals (Sweden)

    Patrick Gérardin

    2014-07-01

    Full Text Available Little is known about the neurocognitive outcome in children exposed to perinatal mother-to-child Chikungunya virus (p-CHIKV infection.The CHIMERE ambispective cohort study compared the neurocognitive function of 33 p-CHIKV-infected children (all but one enrolled retrospectively at around two years of age with 135 uninfected peers (all enrolled prospectively. Psychomotor development was assessed using the revised Brunet-Lezine scale, examiners blinded to infectious status. Development quotients (DQ with subscores covering movement/posture, coordination, language, sociability skills were calculated. Predictors of global neurodevelopmental delay (GND, DQ ≤ 85, were investigated using multivariate Poisson regression modeling. Neuroradiologic follow-up using magnetic resonance imaging (MRI scans was proposed for most of the children with severe forms.The mean DQ score was 86.3 (95%CI: 81.0-91.5 in infected children compared to 100.2 (95%CI: 98.0-102.5 in uninfected peers (P<0.001. Fifty-one percent (n = 17 of infected children had a GND compared to 15% (n = 21 of uninfected children (P<0.001. Specific neurocognitive delays in p-CHIKV-infected children were as follows: coordination and language (57%, sociability (36%, movement/posture (27%. After adjustment for maternal social situation, small for gestational age, and head circumference, p-CHIKV infection was found associated with GND (incidence rate ratio: 2.79, 95%CI: 1.45-5.34. Further adjustments on gestational age or breastfeeding did not change the independent effect of CHIKV infection on neurocognitive outcome. The mean DQ of p-CHIKV-infected children was lower in severe encephalopathic children than in non-severe children (77.6 versus 91.2, P<0.001. Of the 12 cases of CHIKV neonatal encephalopathy, five developed a microcephaly (head circumference <-2 standard deviations and four matched the definition of cerebral palsy. MRI scans showed severe restrictions of white matter areas

  18. A review of advances in molecular biology testing for Chikungunya virus infection%我国基孔肯雅病毒分子生物学检测技术研究进展

    Institute of Scientific and Technical Information of China (English)

    崔新国; 周红宁; 郭晓芳

    2016-01-01

    基孔肯雅热(Chikungunya Fever,CHIK)是由基孔肯雅病毒(Chikungunya virus,CHIKV)感染引起的,经蚊虫叮咬传播的一种人、兽共患急性传染病,主要流行于热带和亚热带地区.人对CHIKV普遍易感,感染后主要临床特征为发热、皮疹和严重的关节痛等症状.实验室检测CHIKV技术主要包括病毒分离技术、血清学试验和分子生物学检测技术,其中,分子生物学检测CHIKV具有快速、准确鉴别和诊断等特点,对于及早发现CHIK病例,防止病例扩散具有重要价值.本文对常见的CHIKV分子生物学检测技术研究进展进行综述.

  19. Chikungunya: a potentially emerging epidemic?

    Directory of Open Access Journals (Sweden)

    Michelle M Thiboutot

    Full Text Available Chikungunya virus is a mosquito-borne emerging pathogen that has a major health impact in humans and causes fever disease, headache, rash, nausea, vomiting, myalgia, and arthralgia. Indigenous to tropical Africa, recent large outbreaks have been reported in parts of South East Asia and several of its neighboring islands in 2005-07 and in Europe in 2007. Furthermore, positive cases have been confirmed in the United States in travelers returning from known outbreak areas. Currently, there is no vaccine or antiviral treatment. With the threat of an emerging global pandemic, the peculiar problems associated with the more immediate and seasonal epidemics warrant the development of an effective vaccine. In this review, we summarize the evidence supporting these concepts.

  20. Laboratory diagnosis of an imported Chikungunya disease case in China%一例输入性基孔肯雅病的实验室诊断

    Institute of Scientific and Technical Information of China (English)

    洪烨; 钟玉清; 幸芦琴; 师永霞; 郑夔; 黄吉城; 李小波; 相大鹏; 郭波旋; 李华; 宋卫; 戴俊

    2008-01-01

    基孔肯雅病(Chikungunya disease)是由基孔肯雅病毒(Chikungunya virus)引起的一种急性传染病,通过伊蚊传播。临床上以发热、关节疼痛、皮疹和轻度出血为特征。基孔肯雅病毒是单股RNA病毒,属于披膜病毒科甲病毒属。基孔肯雅热始发于非洲,1952年,基孔肯雅热被首次报道,主要流行于非洲。到了20世纪60年代以后,基孔肯雅热东移东南亚地区。1965年,印度发生大流行,30万人感染。

  1. Replication cycle of chikungunya: A re-emerging arbovirus

    OpenAIRE

    Solignat, Maxime; Gay, Bernard; Higgs, Stephen; Briant, Laurence; Devaux, Christian

    2009-01-01

    Arboviruses (or arthropod-borne viruses), represent a threat for the new century. The 2005–2006 year unprecedented epidemics of chikungunya virus (CHIKV) in the French Reunion Island in the Indian Ocean, followed by several outbreaks in other parts of the world such as India, have attracted the attention of clinicians, scientists, and state authorities about the risks linked to this re-emerging mosquito-borne virus. CHIKV, which belongs to the Alphaviruses genus, was not previously regarded a...

  2. The Hidden Burden of Dengue and Chikungunya in Chennai, India.

    Directory of Open Access Journals (Sweden)

    Isabel Rodríguez-Barraquer

    Full Text Available Dengue and chikungunya are rapidly expanding viruses transmitted by mosquitoes of the genus Aedes. Few epidemiological studies have examined the extent of transmission of these infections in South India despite an increase in the number of reported cases, and a high suitability for transmission.We conducted a household-based seroprevalence survey among 1010 individuals aged 5-40 years living in fifty randomly selected spatial locations in Chennai, Tamil Nadu. Participants were asked to provide a venous blood sample and to complete a brief questionnaire with basic demographic and daily activity information. Previous exposure to dengue and chikungunya was determined using IgG indirect ELISA (Panbio and IgG ELISA (Novatec, respectively. We used this data to estimate key transmission parameters (force of infection and basic reproductive number and to explore factors associated with seropositivity. While only 1% of participants reported history of dengue and 20% of chikungunya, we found that 93% (95%CI 89-95% of participants were seropositive to dengue virus, and 44% (95%CI 37-50% to chikungunya. Age-specific seroprevalence was consistent with long-tem, endemic circulation of dengue and suggestive of epidemic chikungunya transmission. Seropositivity to dengue and chikungunya were significantly correlated, even after adjusting for individual and household factors. We estimate that 23% of the susceptible population gets infected by dengue each year, corresponding to approximately 228,000 infections. This transmission intensity is significantly higher than that estimated in known hyperendemic settings in Southeast Asia and the Americas.These results provide unprecedented insight into the very high transmission potential of dengue and chikungunya in Chennai and underscore the need for enhanced surveillance and control methods.

  3. Molecular and Virological Investigation of a Focal Chikungunya Outbreak in Northern India

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    Manisha Soni

    2013-01-01

    Full Text Available Chikungunya (CHIK fever is one of the most important arboviral infections of medical significance. The objective of the present study is to identify and characterize the etiology of a focal febrile arthritis outbreak from Gwalior, northern India, during October-November 2010. A detailed virological (isolation and molecular (end-point RT-PCR, quantitative RT-PCR, and nucleotide sequencing investigation of this outbreak was carried out by collecting and studying 52 clinical samples and 15 mosquito pools from the affected region. The investigation revealed the presence of CHIK viral RNA in 29% of clinical samples and 13% mosquito pool by RT-PCR. The quantification of CHIK viral RNA in samples varied from 102.50 to 106.67 copies/mL, as demonstrated through quantitative RT-PCR. In addition, six CHIK viruses were isolated from RT-PCR positive samples. The nucleotide sequences of partial E1 gene of five representative CHIK viruses were deciphered, which revealed that all the viral strains from this outbreak belong to the recently emerging ECS African genotype. Identification of Chikungunya virus ECSA African genotype as the etiology of the present outbreak confirms the continued circulation of the novel genotype, since 2006, in India. The identification of CHIK virus in Aedes aegypti also confirmed it as the major vector in northern India.

  4. Clinical profile of chikungunya patients during the epidemic of 2007 in Kerala, India

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    Krishna Pillai Vijayakumar

    2011-01-01

    Full Text Available Background: The association of the present Chikungunya pandemic with a mutation in the Chik virus is already established in many parts of the world, including Kerala. Kerala was one of the worst-affected states of India in the Chikungunya epidemic of 2006-2007. It is important to discuss the clinical features of patients affected by Chikungunya fever in the context of this change in the epidemiology of the disease. Aim: This study tries to analyze the clinical picture of the Chikungunya patients in Kerala during the epidemic of 2007. Setting and Design: A cross-sectional survey was carried out in five of the most affected districts in Kerala, India. Materials and Methods: A two-stage cluster sampling technique was used to collect the information. Ten clusters each were selected from all the five districts, and the size of the clusters were 18 houses each. A structured interview schedule was used for data collection. Diagnosis based on clinical signs and symptoms was the major case-finding strategy. Results and Conclusion: Of the 3623 residents in the surveyed households, 1913 (52.8% had Chikungunya clinically. Most of the affected were in the adult age group (73.4%. Swelling of the joints was seen in 69.9% of the patients, followed by headache (64.1% and itching (50.3%. The knee joint was the most common joint affected (52%. The number of patients with persistence of any of the symptoms even after 1 month of illness was 1388 (72.6%. Taking bed rest till the relief of joint pain was found to be a protective factor for the persistence of the symptoms. Recurrence of symptoms with a period of disease-free interval was complained by 669 (35.0% people. Older age (>40 years, a presentation of high-grade fever with shivering, involvement of the small joints of the hand, presence of rashes or joint swelling during the first week of fever and fever lasting for more than 1 week were the significant risk factors for recurrence of symptoms predicted by a

  5. Pan-European Chikungunya surveillance: designing risk stratified surveillance zones

    OpenAIRE

    Skelly Chris; Tilston Natasha; Weinstein Phil

    2009-01-01

    Abstract The first documented transmission of Chikungunya within Europe took place in Italy during the summer of 2007. Chikungunya, a viral infection affecting millions of people across Africa and Asia, can be debilitating and no prophylactic treatment exists. Although imported cases are reported frequently across Europe, 2007 was the first confirmed European outbreak and available evidence suggests that Aedes albopictus was the vector responsible and the index case was a visitor from India. ...

  6. Estimated Zika virus importations to Europe by travellers from Brazil

    OpenAIRE

    Massad, Eduardo; Tan, Ser-Han; Khan, Kamran; Wilder-Smith, Annelies

    2016-01-01

    Background: Given the interconnectivity of Brazil with the rest of the world, Zika virus (ZIKV) infections have the potential to spread rapidly around the world via viremic travellers. The extent of spread depends on the travel volume and the endemicity in the exporting country. In the absence of reliable surveillance data, we did mathematical modelling to estimate the number of importations of ZIKV from Brazil into Europe.Design: We applied a previously developed mathematical model on import...

  7. The Chikungunya Virus Capsid Protein Contains Linear B Cell Epitopes in the N- and C-Terminal Regions that are Dependent on an Intact C-Terminus for Antibody Recognition

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    Lucas Y. H. Goh

    2015-06-01

    Full Text Available Chikungunya virus (CHIKV is an arthropod-borne agent that causes severe arthritic disease in humans and is considered a serious health threat in areas where competent mosquito vectors are prevalent. CHIKV has recently been responsible for several millions of cases of disease, involving over 40 countries. The recent re-emergence of CHIKV and its potential threat to human health has stimulated interest in better understanding of the biology and pathogenesis of the virus, and requirement for improved treatment, prevention and control measures. In this study, we mapped the binding sites of a panel of eleven monoclonal antibodies (mAbs previously generated towards the capsid protein (CP of CHIKV. Using N- and C-terminally truncated recombinant forms of the CHIKV CP, two putative binding regions, between residues 1–35 and 140–210, were identified. Competitive binding also revealed that five of the CP-specific mAbs recognized a series of overlapping epitopes in the latter domain. We also identified a smaller, N-terminally truncated product of native CP that may represent an alternative translation product of the CHIKV 26S RNA and have potential functional significance during CHIKV replication. Our data also provides evidence that the C-terminus of CP is required for authentic antigenic structure of CP. This study shows that these anti-CP mAbs will be valuable research tools for further investigating the structure and function of the CHIKV CP.

  8. The Chikungunya Virus Capsid Protein Contains Linear B Cell Epitopes in the N- and C-Terminal Regions that are Dependent on an Intact C-Terminus for Antibody Recognition.

    Science.gov (United States)

    Goh, Lucas Y H; Hobson-Peters, Jody; Prow, Natalie A; Baker, Kelly; Piyasena, Thisun B H; Taylor, Carmel T; Rana, Ashok; Hastie, Marcus L; Gorman, Jeff J; Hall, Roy A

    2015-06-08

    Chikungunya virus (CHIKV) is an arthropod-borne agent that causes severe arthritic disease in humans and is considered a serious health threat in areas where competent mosquito vectors are prevalent. CHIKV has recently been responsible for several millions of cases of disease, involving over 40 countries. The recent re-emergence of CHIKV and its potential threat to human health has stimulated interest in better understanding of the biology and pathogenesis of the virus, and requirement for improved treatment, prevention and control measures. In this study, we mapped the binding sites of a panel of eleven monoclonal antibodies (mAbs) previously generated towards the capsid protein (CP) of CHIKV. Using N- and C-terminally truncated recombinant forms of the CHIKV CP, two putative binding regions, between residues 1-35 and 140-210, were identified. Competitive binding also revealed that five of the CP-specific mAbs recognized a series of overlapping epitopes in the latter domain. We also identified a smaller, N-terminally truncated product of native CP that may represent an alternative translation product of the CHIKV 26S RNA and have potential functional significance during CHIKV replication. Our data also provides evidence that the C-terminus of CP is required for authentic antigenic structure of CP. This study shows that these anti-CP mAbs will be valuable research tools for further investigating the structure and function of the CHIKV CP.

  9. Emerging alphaviruses in the Americas: Chikungunya and Mayaro

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    Mario Luis Garcia de Figueiredo

    2014-12-01

    Full Text Available Chikungunya virus (CHIKV and Mayaro virus (MAYV are emergent arthropod-borne viruses that produce outbreaks of acute febrile illness with arthropathy. Despite their different continental origins, CHIKV and MAYV are closely related and are components of the Semliki Forest Complex of the Alphavirus (Togaviridae. MAYV and, more recently, CHIKV, which are both transmitted by Aedes mosquitoes, have resulted in severe public health problems in the Americas, including Brazil. In this review, we present aspects of the pathogenesis, clinical presentation and treatment of febrile illnesses produced by CHIKV and MAYV. We also discuss the epidemiological aspects and effects related to the prophylaxis of infections by both viruses.

  10. Emergence of chikungunya in Moonlapamok and Khong Districts, Champassak Province, the Lao People’s Democratic Republic, May to September 2012

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    Viengsavanh Kitthiphong

    2013-03-01

    Full Text Available Introduction: Chikungunya is a vector-borne disease transmitted to humans by Aedes mosquitoes, which are widespread in the Lao People’s Democratic Republic. However, chikungunya virus (CHIKV had not been detected in the country before outbreaks reported in July 2012. The first outbreaks were detected through health care worker event-based surveillance. Methods: The case definition for the outbreaks was defined as a person with acute onset of fever (> 38 °C and severe arthralgia (joint pain or arthritis from 1 May 2012 in Champassak Province. Rapid response teams conducted active case finding, performed an environmental assessment including an entomological survey and implemented control measures. Descriptive analysis was undertaken in Microsoft Excel. Results: There were 197 cases (attack rate 3.4% of suspected chikungunya reported from 10 villages in Moonlapamok and Khong Districts of Champassak Province. All age groups (age range: seven months–74 years were affected with slightly more female (56% than male cases. Thirty-one per cent (16 of 52 of serum samples tested positive for CHIKV by polymerase chain reaction. The environmental assessment found poor water storage practices and high entomological indices. Discussion: These outbreaks show the effectiveness of health care worker event-based surveillance and the importance of sharing of information across borders for detecting emerging diseases. Public health education is an important measure to prevent epidemics of chikungunya. Information about chikungunya should be supplied to health care workers in the region so they are alert to the potential spread and are able to implement control measures for this disease.

  11. Chikungunya: epidemiology [version 1; referees: 2 approved

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    Lyle R. Petersen

    2016-01-01

    Full Text Available Chikungunya virus is a mosquito-borne alphavirus that causes fever and debilitating joint pains in humans. Joint pains may last months or years. It is vectored primarily by the tropical and sub-tropical mosquito, Aedes aegypti, but is also found to be transmitted by Aedes albopictus, a mosquito species that can also be found in more temperate climates. In recent years, the virus has risen from relative obscurity to become a global public health menace affecting millions of persons throughout the tropical and sub-tropical world and, as such, has also become a frequent cause of travel-associated febrile illness. In this review, we discuss our current understanding of the biological and sociological underpinnings of its emergence and its future global outlook.

  12. A Within-Host Chikungunya Virus Infection Model with Delay%基孔肯雅病毒在宿主体内的时滞动力学模型

    Institute of Scientific and Technical Information of China (English)

    王艳; 刘贤宁

    2016-01-01

    In this paper ,a within‐host Chikungunya virus infection model with discrete delays is considered and analyzed .Firstly ,the positivity and boundedness of solutions are proved and the basic reproductive number R0 is computed .Secondly ,the existence of equilibria is discussed .There always exists a virus‐free equilibrium point ,and there is a unique endemic equilibrium point when R0 > 1 .Finally ,the global stabili‐ties of the virus‐free equilibrium and endemic equilibrium are obtained by constructing Lyapunov functions .%建立并分析了一个考虑基孔肯雅病毒在宿主体内的离散时滞动力学模型。首先,证明了解的正性和有界性,并计算出基本再生数 R0;其次,讨论了模型平衡点的存在性,得出无感染平衡点始终存在,而当 R0>1时,存在唯一的地方病平衡点;最后,通过构造 Lyapunov 泛函,得到了无病平衡点的全局稳定性及地方病平衡点的全局稳定性。

  13. Importance of mosquito “quasispecies” in selecting an epidemic arthropod-borne virus

    Science.gov (United States)

    Vazeille, Marie; Zouache, Karima; Vega-Rúa, Anubis; Thiberge, Jean-Michel; Caro, Valérie; Yébakima, André; Mousson, Laurence; Piorkowski, Géraldine; Dauga, Catherine; Vaney, Marie-Christine; Manni, Mosè; Gasperi, Giuliano; de Lamballerie, Xavier; Failloux, Anna-Bella

    2016-01-01

    Most arthropod-borne viruses (arboviruses), perpetuated by alternation between a vertebrate host and an insect vector, are likely to emerge through minor genetic changes enabling the virus to adapt to new hosts. In the past decade, chikungunya virus (CHIKV; Alphavirus, Togaviridae) has emerged on La Réunion Island following the selection of a unique substitution in the CHIKV E1 envelope glycoprotein (E1-A226V) of an East-Central-South African (ECSA) genotype conferring a higher transmission rate by the mosquito Aedes albopictus. Assumed to have occurred independently on at least four separate occasions, this evolutionary convergence was suspected to be responsible for CHIKV worldwide expansion. However, assumptions on CHIKV emergence were mainly based on viral genetic changes and the role of the mosquito population quasispecies remained unexplored. Here we show that the nature of the vector population is pivotal in selecting the epidemic CHIKV. We demonstrate using microsatellites mosquito genotyping that Ae. albopictus populations are genetically differentiated, contributing to explain their differential ability to select the E1-226V mutation. Aedes albopictus, newly introduced in Congo coinciding with the first CHIKV outbreak, was not able to select the substitution E1-A226V nor to preferentially transmit a CHIKV clone harboring the E1-226V as did Ae. albopictus from La Réunion. PMID:27383735

  14. Zika virus infection in a traveller returning to Europe from Brazil, March 2015.

    Science.gov (United States)

    Zammarchi, L; Tappe, D; Fortuna, C; Remoli, M E; Günther, S; Venturi, G; Bartoloni, A; Schmidt-Chanasit, J

    2015-06-11

    We report a case of laboratory-confirmed Zika virus infection imported into Europe from the Americas. The patient developed fever, rash, and oedema of hands and feet after returning to Italy from Brazil in late March 2015. The case highlights that, together with chikungunya virus and dengue virus, three major arboviruses are now co-circulating in Brazil. These arboviruses represent a burden for the healthcare systems in Brazil and other countries where competent mosquito vectors are present.

  15. Zoonotic viruses associated with illegally imported wildlife products.

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    Kristine M Smith

    Full Text Available The global trade in wildlife has historically contributed to the emergence and spread of infectious diseases. The United States is the world's largest importer of wildlife and wildlife products, yet minimal pathogen surveillance has precluded assessment of the health risks posed by this practice. This report details the findings of a pilot project to establish surveillance methodology for zoonotic agents in confiscated wildlife products. Initial findings from samples collected at several international airports identified parts originating from nonhuman primate (NHP and rodent species, including baboon, chimpanzee, mangabey, guenon, green monkey, cane rat and rat. Pathogen screening identified retroviruses (simian foamy virus and/or herpesviruses (cytomegalovirus and lymphocryptovirus in the NHP samples. These results are the first demonstration that illegal bushmeat importation into the United States could act as a conduit for pathogen spread, and suggest that implementation of disease surveillance of the wildlife trade will help facilitate prevention of disease emergence.

  16. Chikungunya: unos meses después del ataque

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    Salim Mattar V.

    2015-01-01

    Full Text Available In May of 2014, the editorial of the MVZ Cordoba magazine announced the warning of the inevitable arrival of the Chikungunya virus to Colombia, especially in the Caribbean region given its climatic conditions of tropical humidity, as well as the presence of the well known competent vector of dengue: Aedes aegypti (1. The abundant population of this mosquito in the Caribbean allowed a quick adaptation of the Chikungunya virus and facilitated its dissemination throughout the entire Atlantic coast. The OPS (Pan-American Health Organization and the Ministry of Health of Colombia knew of its imminent arrival and allocated resources to control the vector and mitigate the epidemiologic impact of this new arbovirus. However, it has been observed that the fumigation campaigns were not systematic and did not even take place in some rural populations of the Atlantic coast.

  17. Estimated Zika virus importations to Europe by travellers from Brazil

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    Eduardo Massad

    2016-05-01

    Full Text Available Background: Given the interconnectivity of Brazil with the rest of the world, Zika virus (ZIKV infections have the potential to spread rapidly around the world via viremic travellers. The extent of spread depends on the travel volume and the endemicity in the exporting country. In the absence of reliable surveillance data, we did mathematical modelling to estimate the number of importations of ZIKV from Brazil into Europe. Design: We applied a previously developed mathematical model on importations of dengue to estimate the number of ZIKV importations into Europe, based on the travel volume, the probability of being infected at the time of travel, the population size of Brazil, and the estimated incidence of ZIKV infections. Results: Our model estimated between 508 and 1,778 imported infections into Europe in 2016, of which we would expect between 116 and 355 symptomatic Zika infections; with the highest number of importations being into France, Portugal and Italy. Conclusions: Our model identified high-risk countries in Europe. Such data can assist policymakers and public health professionals in estimating the extent of importations in order to prepare for the scale up of laboratory diagnostic assays and estimate the occurrence of Guillain–Barré Syndrome, potential sexual transmission, and infants with congenital ZIKV syndrome.

  18. Estimated Zika virus importations to Europe by travellers from Brazil

    Science.gov (United States)

    Massad, Eduardo; Tan, Ser-Han; Khan, Kamran; Wilder-Smith, Annelies

    2016-01-01

    Background Given the interconnectivity of Brazil with the rest of the world, Zika virus (ZIKV) infections have the potential to spread rapidly around the world via viremic travellers. The extent of spread depends on the travel volume and the endemicity in the exporting country. In the absence of reliable surveillance data, we did mathematical modelling to estimate the number of importations of ZIKV from Brazil into Europe. Design We applied a previously developed mathematical model on importations of dengue to estimate the number of ZIKV importations into Europe, based on the travel volume, the probability of being infected at the time of travel, the population size of Brazil, and the estimated incidence of ZIKV infections. Results Our model estimated between 508 and 1,778 imported infections into Europe in 2016, of which we would expect between 116 and 355 symptomatic Zika infections; with the highest number of importations being into France, Portugal and Italy. Conclusions Our model identified high-risk countries in Europe. Such data can assist policymakers and public health professionals in estimating the extent of importations in order to prepare for the scale up of laboratory diagnostic assays and estimate the occurrence of Guillain–Barré Syndrome, potential sexual transmission, and infants with congenital ZIKV syndrome. PMID:27193266

  19. The Hidden Burden of Dengue and Chikungunya in Chennai, India

    OpenAIRE

    Rodríguez-Barraquer, Isabel; Solomon, Sunil S.; Kuganantham, Periaswamy; Srikrishnan, Aylur Kailasom; Vasudevan, Canjeevaram K; Iqbal, Syed H.; Balakrishnan, Pachamuthu; Solomon, Suniti; Mehta, Shruti H.; Cummings, Derek A. T.

    2015-01-01

    Background Dengue and chikungunya are rapidly expanding viruses transmitted by mosquitoes of the genus Aedes. Few epidemiological studies have examined the extent of transmission of these infections in South India despite an increase in the number of reported cases, and a high suitability for transmission. Methods and findings We conducted a household-based seroprevalence survey among 1010 individuals aged 5-40 years living in fifty randomly selected spatial locations in Chennai, Tamil Nadu. ...

  20. Dissemination and transmission of the E1-226V variant of chikungunya virus in Aedes albopictus are controlled at the midgut barrier level.

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    Camilo Arias-Goeta

    Full Text Available Emergence of arboviruses could result from their ability to exploit new environments, for example a new host. This ability is facilitated by the high mutation rate occurring during viral genome replication. The last emergence of chikungunya in the Indian Ocean region corroborates this statement since a single viral mutation at the position 226 on the E1 glycoprotein (E1-A226V was associated with enhanced transmission by the mosquito Aedes albopictus in regions where the major mosquito vector, Aedes aegypti, is absent.We used direct competition assays in vivo to dissect out the mechanisms underlying the selection of E1-226V by Ae. albopictus. When the original variant E1-226A and the newly emerged E1-226V were provided in the same blood-meal at equal titers to both species of mosquitoes, we found that the proportion of both variants was drastically different in the two mosquito species. Following ingestion of the infectious blood-meal, the E1-226V variant was preferentially selected in Ae. albopictus, whereas the E1-226A variant was sometimes favored in Ae. aegypti. Interestingly, when the two variants were introduced into the mosquitoes by intrathoracic inoculations, E1-226V was no longer favored for dissemination and transmission in Ae. albopictus, showing that the midgut barrier plays a key role in E1-226V selection.This study sheds light on the role of the midgut barrier in the selection of novel arbovirus emerging variants. We also bring new insight into how the pre-existing variant E1-226V was selected among other viral variants including E1-226A. Indeed the E1-226V variant present at low levels in natural viral populations could rapidly emerge after being selected in Ae. albopictus at the midgut barrier level.

  1. Preparation, characterization and immunogenicity analysis of Chikungunya virus-like particles produced in insect cells%基孔肯雅病毒样颗粒的制备及免疫原性研究

    Institute of Scientific and Technical Information of China (English)

    李建东; 张全福; 张硕; 李川; 刘琴芝; 梁米芳; 李德新

    2015-01-01

    目的 评价基孔肯雅病毒(CHIKV)病毒样颗粒(VLPs)免疫原性.方法 通过构建CHIKV结构蛋白编码基因C-E3-E2-6K-E1昆虫细胞表达载体,然后与杆状病毒线性DNA共转染SF9昆虫细胞制备重组杆状病毒,感染悬浮培养的SF9细胞制备VLPs.IFA、SDS-PAGE和Western-Blot法对表达产物进行鉴定分析,用纯化VLPs免疫BALB/c小鼠,评价免疫原性.结果 CHIKV结构蛋白装配形成病毒样球形颗粒,免疫小鼠可诱导CHIKV特异性抗体,能够有效中和CHIKV感染Vero细胞.结论 CHIKV VLPs能够通过杆状病毒系统在昆虫细胞中有效分泌表达,并具有较强免疫原性,为基于CHIKV VLPs的免疫学检测试剂乃至疫苗的研制奠定了基础.%Objective To prepare the virus-like particles (VLPs) of Chikungunya virus (CHIKV) and evaluate the immunogenicity.Method CHIKV structural protein C-E3-E2-6K-E1 encoding gene were amplified by fusion PCR,and cloned into an insect cell expression vector.The recombinant Baculovirus were recovered by co-transfection of the expression plasmid with baculovirus linear DNA into SF9 insect cells,and CHIKV VLPs were prepared from suspension culture SF9 cells.Structural proteins expression were analyzed using IFA,SDS-PAGE and Western-Blot,and morphological analysis via electron microscopy.Result Which showed that CHIKV structural proteins were secreted into the cell culture supernatant and assembled into virus-like spherical particles.BALB /c mice were immunized with the VLPs,high levels of CHIKV specific antibodies were detected in the sera,and CHIKV infection of Vero cells could be effectively neutralized.Couclusion The results showed that CHIKV VLPs can be efficiently produced by the baculovirus expression system in insect cells,and specific IgG and neutralization antibodies could be induced in mice after VLPs immunization.This research laid the foundation for the development of CHIKV VLPs based on immunological detection reagents and even vaccines.

  2. Molecular genetic analysis of two Chikungunya virus strains isolated in Shenzhen%深圳市新分离两株基孔肯雅热病毒的分子遗传学分析

    Institute of Scientific and Technical Information of China (English)

    许少坚; 任燕; 孙华杰; 李贻汉; 蔡剑辉; 何小媚; 白江涛; 阳帆; 王金明

    2015-01-01

    目的 对2010~2012年深圳市报告的两起输入性基孔肯雅热病原体进行分子遗传学分析.方法 利用C6/36细胞从病人血清中分离基孔肯雅病毒(Chikungunya virus,CHIKV),对分离得到的CHIKV进行全基因组测序和构建系统发生树,结合流行病学资料对其分子遗传特征进行分析.结果 成功分离得到两株CHIKV,分别命名为SZ_20101028和SZ 20120702,SZ_20101028全基因组长为12377bp,SZ_20120823全基因组长为11893bp;构建系统发生树分析,结果表明,SZ_20101028是印度洋亚型,ECSA型的后裔.SZ_20120702为Asian亚型.结论 SZ_20101028与最近10年来在印度洋岛屿爆发流行新亚型且与2010年由输入性引发起东莞疫情爆发的毒株亲源性最高,为99%;而SZ_20120702为Asian亚型,不是近年来爆发流行株.

  3. 基孔肯雅病毒的纳米金实时荧光PCR方法的建立%Development of gold nanoparticle-assisted real-time fluorescence PCR for quantitative detection of Chikungunya viruses

    Institute of Scientific and Technical Information of China (English)

    燕清丽; 杨鹏飞; 房健慧; 张丽萍; 张晓龙; 曹晓梅; 姚李四

    2012-01-01

    目的 建立一种检测基孔肯雅病毒纳米金实时荧光定量PCR的方法.方法 以课题组建立的普通实时荧光PCR方法为基础,在PCR体系中添加不同大小粒径的纳米金进行体系优化,评价优化后的体系.结果 添加纳米金的实时荧光PCR较不添加的扩增效率高;优化后的纳米金实时荧光PCR产物的Ct值与模板稀释浓度存在良好的线性关系,回归方程:y=-3.31x+41.78,R2=0.9997,PCR扩增效率为99.5%.结论 纳米金能提高实时荧光PCR的反应效率.%Objective To develop a gold nanoparticle-assisted real-time fluorescence PCR array for quantitative detection of Chikungunya viruses. Methods On the basis of the real-time PCR that we had established, gold nanoparticles of different sizes were added to the system for optimization, which was then evaluated. Results It was found that the amplification efficacy of the system with gold nanoparticles was higher than that without gold nanoparticles, amounting to 99.5%. There existed a good linear relationship between the Ct value of the products by gold nanoparticle-assisted real-time fluorescence PCR and the concentrations of templates, with the regression equation being y=-3.31x+ 41.78,R2=0.9997. Conclusion Gold nanoparticle-assisted realtime fluorescence PCR has the potential to improve the efficiency of PCR amplification.

  4. Multiple sequence alignment and phylogenetic analysis of complete genome of Chikungunya virus%基孔肯雅病毒全基因组的多序列比对及遗传进化分析

    Institute of Scientific and Technical Information of China (English)

    龙遗芳; 柯昌文; 郭中敏; 陆家海

    2015-01-01

    目的 了解基孔肯雅病毒(Chikungunya virus,CHIKV)毒株的时间、地区及基因型的分布情况,不同时间和地区分离毒株的相似性,核苷酸位点的变异情况以及病毒的遗传进化趋势,为基孔肯雅热的预防和控制奠定基础.方法 对美国国立生物技术信息中心(NCBI)中收录的CHIKV毒株全基因组序列共133条用DNAStar7.1软件进行核苷酸和氨基酸相似性比较及变异分析,用Mega 6.06进行遗传进化分析.结果 CHIKV组内核苷酸序列相似性在97.7% ~ 100.0%之间,CHIKV组内氨基酸序列相似性在80.3% ~ 100.0%之间,组内相似性较高,变异率较低;CHIKV碱基间的转换较为常见占碱基突变的81.02%;分离时间、地区相近的毒株遗传距离较近,不同谱系的东/中/南非型毒株已蔓延至欧亚各地区.结论 CHIKV毒株存在一定的变异,但具有较高的遗传稳定性.

  5. A review of advances in normal serology testing for Chikungunya virus infection%基孔肯雅病毒常见血清学检测技术研究进展

    Institute of Scientific and Technical Information of China (English)

    杨晓羽; 周红宁; 郭晓芳

    2014-01-01

    基孔肯雅热是由基孔肯雅病毒(Chikungunya virus,CHIKV)经伊蚊叮咬传播的一种自然疫源性疾病,人群普遍对CHIKV易感,临床上多以突起发热、皮疹、关节疼痛和轻度出血为主要特征,主要分布在非洲、南亚、东南亚热带和亚热带地区.由于目前无疫苗预防和特效药治疗,及时开展疑似CHIK病例实验室诊断检测,防止其暴发与流行具有重要的意义.现今实验室检测CHIKV感染技术主要包括血清学试验、病毒分离技术和分子生物学检测技术,其中前者具有操作简便、快速特点,较容易现场推广应用.常见的血清学检测方法主要包括中和试验(Neutralization test,NT)、血凝抑制试验(Hemagglutimation inhibition test,HI)、酶联免疫吸附试验(Enzyme-linked immunosorbent assay,ELISA)、免疫层析试验(Immunochromatography assay,ICA)、间接免疫荧光试验(Indirect immunofluorescence assay,IFA)等.本文对上述常见的基孔肯稚血清学检测方法进行了综述.

  6. Dengue, chikungunya … and the missing entity - Zika fever: A new emerging threat.

    Science.gov (United States)

    Tilak, Rina; Ray, Sougat; Tilak, V W; Mukherji, Sandip

    2016-04-01

    Zika virus (ZIKV), a relative newcomer from the flavivirus group that includes dengue, Japanese encepahalitis and yellow fever, is one of the emerging pathogens that is fast transcending geographical boundaries. It is a vector-borne disease transmitted by the same Aedes aegypti and Aedes albopictus, which cause dengue and chikungunya. In addition to the vector-mediated transmission of Zika fever, probable human-to-human transmission through exchange of body fluids, including sexual and perinatal transmission and through blood transfusion, makes containment of this new entity more challenging. Moreover, a high index of suspicion by an astute physician is necessary for diagnosis of Zika fever in view of the similarity of symptoms with dengue and chikungunya, especially in areas, where these two diseases are already endemic. Zika, till recently, has had minimal impact, but its true potential is unfolding with increasing detection of congenital malformities, Guillain-Barré syndrome and other neurological and autoimmune syndromes in patients with recent history of ZIKV infection, or when mothers get infected with Zika during first or second trimester of pregnancy. The association, however, needs to be established, nonetheless it is important that we keep a close vigil on this emerging vector borne disease - the 'ZIKA' fever. PMID:27257326

  7. Complete Genome Sequence of Zika Virus from the First Imported Case in Mainland China

    OpenAIRE

    Liu, Lin; Wu, Wei; Zhao, Xiang; Xiong, Ying; Zhang, Shuo; Liu, Xiaoqing; Qu, Jing; Li, Jiandong; Nei, Kai; Liang, Mifang; Shu, Yuelong; Hu, Guoliang; Ma, Xuejun; Li, Dexin

    2016-01-01

    The first case of Zika virus infection was identified in a Chinese traveler returning from Venezuela in February 2016. This report describes the complete genome sequence of Zika virus from the first imported case in China. The genome sequence analysis showed that the Zika virus isolated in this case belongs to the Asian lineage.

  8. Transmission potential of Zika virus infection in the South Pacific

    Directory of Open Access Journals (Sweden)

    Hiroshi Nishiura

    2016-04-01

    Conclusions: The transmissibility of Zika virus infection appears to be comparable to those of dengue and chikungunya viruses. Considering that Aedes species are a shared vector, this finding indicates that Zika virus replication within the vector is perhaps comparable to dengue and chikungunya.

  9. [Important aspects of virus safety of advanced therapy medicinal products].

    Science.gov (United States)

    Blümel, J; Stühler, A

    2010-01-01

    Virus safety of advanced therapy medicinal products is a particular challenge. These products may consist of whole cells and the manufacture of these is performed using various human or animal-derived starting materials and reagents. Therefore, extensive testing of donors and of established cell banks is required. Furthermore, the virus safety of reagents such as bovine sera, porcine trypsin, and growth factors needs to be considered. Whenever possible, manufacturing steps for inactivation or removal of viruses should be introduced. However, it is not possible to introduce such steps for cell-based medicinal products as the activity and viability of cells will be compromised. Only in the production of small and stable non-enveloped viral gene vectors is it conceivable to implement steps to selectively inactivate or remove potential contaminating enveloped viruses.

  10. Importance of respiratory viruses in acute otitis media.

    Science.gov (United States)

    Heikkinen, Terho; Chonmaitree, Tasnee

    2003-04-01

    Acute otitis media is usually considered a simple bacterial infection that is treated with antibiotics. However, ample evidence derived from studies ranging from animal experiments to extensive clinical trials supports a crucial role for respiratory viruses in the etiology and pathogenesis of acute otitis media. Viral infection of the upper respiratory mucosa initiates the whole cascade of events that finally leads to the development of acute otitis media as a complication. The pathogenesis of acute otitis media involves a complex interplay between viruses, bacteria, and the host's inflammatory response. In a substantial number of children, viruses can be found in the middle-ear fluid either alone or together with bacteria, and recent studies indicate that at least some viruses actively invade the middle ear. Viruses appear to enhance the inflammatory process in the middle ear, and they may significantly impair the resolution of otitis media. Prevention of the predisposing viral infection by vaccination against the major viruses would probably be the most effective way to prevent acute otitis media. Alternatively, early treatment of the viral infection with specific antiviral agents would also be effective in reducing the occurrence of acute otitis media.

  11. Two novel epistatic mutations (E1:K211E and E2:V264A) in structural proteins of Chikungunya virus enhance fitness in Aedes aegypti.

    Science.gov (United States)

    Agarwal, Ankita; Sharma, Ajay Kumar; Sukumaran, D; Parida, Manmohan; Dash, Paban Kumar

    2016-10-01

    Expansion of CHIKV outbreaks with appearance of novel mutations are reported from many parts of the world. Two novel mutations viz. E1:K211E and E2:V264A in background of E1:226A are recently identified from Aedes aegypti dominated areas of India. In this study, the role of these mutations in modulation of infectivity, dissemination and transmission by two different Aedes species was studied. Mutations were sequentially constructed in CHIKV genome and female Ae. aegypti and Aedes albopictus mosquitoes were orally infected with eight different CHIKV mutants. Double mutant virus containing E1:K211E and E2:V264A mutations in background of E1:226A revealed remarkably higher fitness for Ae. aegypti, as indicated by significant increase in virus infectivity (13 fold), dissemination (15 fold) and transmission (62 fold) compared to parental E1:226A virus. These results indicate that adaptive mutations in CHIKV are leading to efficient CHIKV circulation in Ae. aegypti endemic areas, contributing and sustaining the major CHIKV outbreaks. PMID:27423270

  12. Isolation of Zika Virus Imported from Tonga into Australia

    Science.gov (United States)

    Pyke, Alyssa T.; Moore, Peter R.; Hall-Mendelin, Sonja; McMahon, Jamie L.; Harrower, Bruce J; Constantino, Tanya R; van den Hurk, Andrew F

    2016-01-01

    Introduction: The globally emergent Zika virus (ZIKV) is a threat to Australia, given the number of imported cases from epidemic regions and the presence of competent mosquito vectors. We report the isolation of ZIKV from a female traveler who recently returned from Tonga to Brisbane, Queensland, Australia in 2016. Methods: A specific TaqMan real-time reverse transcriptase polymerase chain reaction assay (RT-PCR) assay was used to detect ZIKV in serum and urine samples. Conventional cell culture techniques and suckling mice were employed in an attempt to isolate ZIKV from serum and urine. Results: A ZIKV isolate (TS17-2016) was recovered from the serum sample after one passage in suckling mouse brains and harvested 11 days post inoculation. Phylogenetic analysis of complete envelope (E) gene sequences demonstrated TS17-2016 shared 99.9% nucleotide identity with other contemporary sequences from Tonga 2016, Brazil 2015 and French Polynesia 2013 within the Asian lineage. Discussion: This is the first known report of successful isolation of ZIKV from a human clinical sample in Australia and the first from a traveler from Tonga. This study highlights the potential difficulties in isolating ZIKV from acute clinical samples using conventional cell culture techniques, particularly in non-endemic countries like Australia where access to samples of sufficient viral load is limited. The successful isolation of TS17-2016 will be essential for continued investigations of ZIKV transmission and pathogenicity and will enable the advancement of new preventative control measures extremely relevant to the Australian and Pacific region. PMID:27679739

  13. First case of imported Zika virus infection in Spain.

    Science.gov (United States)

    Bachiller-Luque, Pablo; Domínguez-Gil González, Marta; Álvarez-Manzanares, Jesús; Vázquez, Ana; De Ory, Fernando; Sánchez-Seco Fariñas, M Paz

    2016-04-01

    We report a case of Zika virus (ZIKV) infection in a patient with diarrhea, fever, synovitis, non-purulent conjunctivitis, and with discreet retro-orbital pain, after returning from Colombia in January 2016. The patient referred several mosquito bites. Presence of ZIKV was detected by PCR (polymerase chain reaction) in plasma. Rapid microbiological diagnosis of ZIKV infection is needed in European countries with circulation of its vector, in order to avoid autochthonous circulation. The recent association of ZIKV infection with abortion and microcephaly, and a Guillain-Barré syndrome highlights the need for laboratory differentiation of ZIKV from other virus infection. Women with potential risk for Zika virus infection who are pregnant or planning to become pregnant must mention that fact during prenatal visits in order to be evaluated and properly monitored. PMID:26994814

  14. First case of imported Zika virus infection in Spain.

    Science.gov (United States)

    Bachiller-Luque, Pablo; Domínguez-Gil González, Marta; Álvarez-Manzanares, Jesús; Vázquez, Ana; De Ory, Fernando; Sánchez-Seco Fariñas, M Paz

    2016-04-01

    We report a case of Zika virus (ZIKV) infection in a patient with diarrhea, fever, synovitis, non-purulent conjunctivitis, and with discreet retro-orbital pain, after returning from Colombia in January 2016. The patient referred several mosquito bites. Presence of ZIKV was detected by PCR (polymerase chain reaction) in plasma. Rapid microbiological diagnosis of ZIKV infection is needed in European countries with circulation of its vector, in order to avoid autochthonous circulation. The recent association of ZIKV infection with abortion and microcephaly, and a Guillain-Barré syndrome highlights the need for laboratory differentiation of ZIKV from other virus infection. Women with potential risk for Zika virus infection who are pregnant or planning to become pregnant must mention that fact during prenatal visits in order to be evaluated and properly monitored.

  15. Cytokines in acute chikungunya.

    Directory of Open Access Journals (Sweden)

    Anuradha Venugopalan

    Full Text Available Acute chikungunya (CHIKV is predominantly an acute onset of excruciatingly painful, self-limiting musculoskeletal (MSK arbovirus illness and this was further reported by us during the 2006 Indian epidemic [Chopra et al. Epidemiol Infect 2012]. Selected serum cytokines profile in subjects within one month of onset of illness is being presented.Out of 509 clinical CHIKV cases (43% population identified during a rural population survey, 225 subjects consented blood investigations. 132 examined within 30 days of febrile onset are the study cohort. Anti-CHIKV IgM and IgG antibodies tested by immunochromatography and indirect immunofluorescence respectively. Interferons (IFN-α, -β and -γ, Interferon Gamma-Induced Protein-10 (CXCL-10/IP-10, Tumor Necrosis Factor-α (TNF-α, Interleukin-1β (IL-1β, Interleukin-6 (IL-6, Interleukin-13 (IL-13, Monocyte Chemoattractant Protein-1 (MCP-1, Interleukin-4 (IL-4 and Interleukin-10 (IL-10 performed by ELISA. Samples collected from neighboring community a year prior to the epidemic used as healthy controls.Seropositivity for anti-CHIKV IgM and IgG was 65% and 52% respectively. IFN-α, IFN-β, IFN-γ, CXCL10/IP-10 and IL-1β showed intense response in early acute phase. Cytokines (particularly TNF-α, MCP-1, IL-4, IL-6 and IL-10 was maximum in extended symptomatic phase and remained elevated in recovered subjects. Higher (p<0.05 IFN and IL-4 seen in patients seropositive for anti-CHIKV IgG. Elderly cases (≥65 years showed elevated cytokines (except IFN and anti-CHIKV antibodies near similar to younger subjects. Significant correlations (p<0.05 found between cytokines and clinical features (fatigue, low back ache, myalgia and anti-CHIKV antibodies.An intense cytokine milieu was evident in the early and immediate persistent symptomatic phase and in recovered subjects. Early persistent IgM and lower IgG to anti-CHKV and intense Th2 cytokine phenotype seem to be associated with delay in resolution of MSK symptoms

  16. Congenital and perinatal complications of chikungunya fever: a Latin American experience

    Directory of Open Access Journals (Sweden)

    Jaime R. Torres

    2016-10-01

    Conclusions: This study presents the largest number of symptomatic neonates with CHIKF analyzed so far in any region and is the first involving infection with the Asian genotype of CHIKV. Although the clinical manifestations found were similar to those reported previously, the percentage of neurological complications was lower. The CFR was comparatively high. Chikungunya represented a substantial risk for neonates born to symptomatic parturients during the chikungunya outbreak in the Americas Region, with important clinical and public health implications.

  17. Zika virus and the risk of imported infection in returned travelers: Implications for clinical care.

    Science.gov (United States)

    Goorhuis, Abraham; von Eije, Karin J; Douma, Renée A; Rijnberg, Noor; van Vugt, Michele; Stijnis, Cornelis; Grobusch, Martin P

    2016-01-01

    Since late 2015, an unprecedented outbreak of Zika virus is spreading quickly across Southern America. The large size of the current outbreak in The Americas will also result in an increase in Zika virus infections among travelers returning from endemic areas. We report five cases of imported Zika virus infection to The Netherlands. Although the clinical course is usually mild, establishing the diagnosis is important, mainly because of the association with congenital microcephaly and the possibility of sexual transmission.

  18. Morphological and Molecular Genetic Characteristics of Chikungunya Virus%深圳市首例基孔肯雅病毒的形态学及分子遗传特征分析

    Institute of Scientific and Technical Information of China (English)

    许少坚; 张仁利; 罗敏; 张倩; 阳帆; 刘涛; 黄达娜; 吴春利; 胡章立; 柯昌文

    2012-01-01

    Objective To analyze the morphological and genetic characteristics of the chikungunya virus (CHIKV) , and provide basic information for further genomit: and proteomic analysis, and vaccine research and development. Methods C6/36 cells were used for the isolation of CHIKV from patient serum and BHK-21 cells were used for the propagation of the virus. The viral particles were concentrated using 7% PEG8000. CHIKV microstructure was studied by ultrathin sections and negative staining. Whole genome was sequenced and phylogenetic tree was constructed based on the genome sequence. Results CHIKV was successfully isolated and concentrated. CHtKV (named SZ-20101028) which was isolated from the sera is belong to the E1-A226 mutant strain, with a genome size of 12 377bp. The virus is a new subtype of the recent 10 years outbreak in the Indian Ocean islands. Conclusion A new subtype of CHIKV was isolated and propagated in laboratory conditions. The morphology and genome sequence were studied, which provide basic information for further genomic and proteomic analysis, and vaccine research and development.%目的 对深圳市首发基孔肯雅病毒(CHIKV)进行分离、增殖培养、浓缩、形态学观察及构建系统发生树分析,为后续基因组信息解析、蛋白组分析、单克隆抗体制备及疫苗研发等应用性研究提供实验基础.方法 利用C6/36细胞从病人血清中分离CHIKV,采用BHK-21细胞对CHIKV进行大量的增殖培养,经7%PEG8000浓缩,超薄切片和负染观察CHIKV显微结构;对分离得到的CHIKV株进行全基因组测序和构建系统发生树,结合流行病学资料对其分子遗传特征进行分析.结果 CHIKV被成功分离并浓缩;在透射电镜下观察CHIKV的直径约为70 nm,圆形有包膜,表面有纤突;CHIKV(SZ-20101028)基因组长为12 377bp,属于E1-A226突变株;该病毒是最近10年来在印度洋岛屿爆发流行的新亚型,与流行病学调查资料相吻合.结论 以现有的条

  19. Congenital Chikungunya with Centro-facial Pigmentation and Persistent Thrombocytopenia: A Case Report

    Directory of Open Access Journals (Sweden)

    Shilpa Kalane

    2015-05-01

    Full Text Available Hyperpigmentation over face in a neonate is rare and the differentials for the same are also rare. Congenital chickengunya, fungal and viral infections, drug rash are few differentials. Chikungunya virus (CHIKV infection manifesting in neonates is very rare. The prevalence of the entity was described only recently. We describe a neonate with hyperpigmentation on day 3 of life with stormy course thereafter. The distinguishing rash on face helped us in clinching the diagnosis of congenital chikungunya and fungal sepsis. Identification of this entity was based on characteristic skin rash and epidemiological background.

  20. A study on Chikungunya outbreak of 2009 in Balussery, Kozhikode, India

    Directory of Open Access Journals (Sweden)

    Meenakshi K. Deepa

    2011-02-01

    Full Text Available Objective: Chikungunya is a viral disease caused by the Chikungunya virus, belonging to the genus Alphavirus of the family Togaviridae. In Kerala the first Chikungunya outbreak occurred in 2006 affecting 14 districts. The re-emergence of the disease occurred in Kozhikode district in Kerala in May 2009. A survey was undertaken in Panangad village, which was the worst affected location. The aim of the survey was to understand the nature and magnitude of the Chikungunya fever, the clinical signs and symptoms. Methods: A total number of 436 cases were surveyed door to door in 7 different localities in the Panangad village of Balussery of Kozhikode district. The patient history, clinical signs and symptoms of the Chikungunya cases were recorded. The signs and symptoms recorded consisted of fever, chills, arthalgia, eye pain, back pain, headache, edema, rash, oral ulcers, hyperpigmentation, itch, myalgia, sore throat, distaste, photophobia, nausea, vomiting, diarrhea, neck pain, hypotension, dermatitis, and dizziness. Results: The major symptoms were fever (100%, arthralgia (81.65%, and myalgia (77.98%. Significant differences were observed in the following symptoms: chills (15.36%, eye pain (7.56%, back pain (30.96%, headache (41.28%, edema (50.68%, rash (29.58%, oral ulcer (14.9%, itch (42.88%, hyperpigmentation (4.58%, sore throat (8.71%, distaste (6.88%, nausea (6.65%, vomiting (12.61%, diarrhea (1.37%, neck pain (0.91%, and dizziness (3.21%. The Chikungunya cases were more severely affected with more or less all of the above mentioned symptoms in the higher age group (>45 years compared to the lower age group (1-30 years. Conclusion: Chikungunya was found to be the major vector born disease in Kerala state. The major clinical symptoms in affected cases were fever, edema, myalgia, and arthralgia. [J Exp Integr Med 2011; 1(1: 59-62

  1. Human Antibody Response to Aedes albopictus Salivary Proteins: A Potential Biomarker to Evaluate the Efficacy of Vector Control in an Area of Chikungunya and Dengue Virus Transmission

    Directory of Open Access Journals (Sweden)

    Souleymane Doucoure

    2014-01-01

    Full Text Available Aedes borne viruses represent public health problems in southern countries and threat to emerge in the developed world. Their control is currently based on vector population control. Much effort is being devoted to develop new tools to control such arbovirus. Recent findings suggest that the evaluation of human antibody (Ab response to arthropod salivary proteins is relevant to measuring the level of human exposure to mosquito bites. Using an immunoepidemiological approach, the present study aimed to assess the usefulness of the salivary biomarker for measuring the efficacy of Ae. albopictus control strategies in La Reunion urban area. The antisaliva Ab response of adult humans exposed to Ae. albopictus was evaluatedbefore and after vector control measures. Our results showed a significant correlation between antisaliva Ab response and the level of exposure to vectors bites. The decrease of Ae. albopictus density has been detected by this biomarker two weeks after the implementation of control measures, suggesting its potential usefulness for evaluating control strategies in a short time period. The identification of species specific salivary proteins/peptides should improve the use of this biomarker.

  2. Human antibody response to Aedes albopictus salivary proteins: a potential biomarker to evaluate the efficacy of vector control in an area of Chikungunya and Dengue Virus transmission.

    Science.gov (United States)

    Doucoure, Souleymane; Mouchet, François; Cornelie, Sylvie; Drame, Papa Makhtar; D'Ortenzio, Eric; DeHecq, Jean Sébastien; Remoue, Franck

    2014-01-01

    Aedes borne viruses represent public health problems in southern countries and threat to emerge in the developed world. Their control is currently based on vector population control. Much effort is being devoted to develop new tools to control such arbovirus. Recent findings suggest that the evaluation of human antibody (Ab) response to arthropod salivary proteins is relevant to measuring the level of human exposure to mosquito bites. Using an immunoepidemiological approach, the present study aimed to assess the usefulness of the salivary biomarker for measuring the efficacy of Ae. albopictus control strategies in La Reunion urban area. The antisaliva Ab response of adult humans exposed to Ae. albopictus was evaluated before and after vector control measures. Our results showed a significant correlation between antisaliva Ab response and the level of exposure to vectors bites. The decrease of Ae. albopictus density has been detected by this biomarker two weeks after the implementation of control measures, suggesting its potential usefulness for evaluating control strategies in a short time period. The identification of species specific salivary proteins/peptides should improve the use of this biomarker. PMID:24822216

  3. Simple clinical and laboratory predictors of Chikungunya versus dengue infections in adults.

    Directory of Open Access Journals (Sweden)

    Vernon J Lee

    Full Text Available BACKGROUND: Dengue and chikungunya are co-circulating vector-borne diseases with substantial overlap in clinical presentations. It is important to differentiate between them during first presentation as their management, especially for dengue hemorrhagic fever (DHF, is different. This study compares their clinical presentation in Singapore adults to derive predictors to assist doctors in diagnostic decision-making. METHODS: We compared 117 patients with chikungunya infection diagnosed with reverse transcription-polymerase chain reaction (RT-PCR with 917 dengue RT-PCR-positive adult patients (including 55 with DHF. We compared dengue fever (DF, DHF, and chikungunya infections by evaluating clinical characteristics of dengue and chikungunya; developing classification tools via multivariate logistic regression models and classification trees of disease etiology using clinical and laboratory factors; and assessing the time course of several clinical variables. FINDINGS: At first presentation to hospital, significantly more chikungunya patients had myalgia or arthralgia, and fewer had a sore throat, cough (for DF, nausea, vomiting, diarrhea, abdominal pain, anorexia or tachycardia than DF or DHF patients. From the decision trees, platelets <118 × 10(9/L was the only distinguishing feature for DF versus chikungunya with an overall correct classification of 89%. For DHF versus chikungunya using platelets <100 × 10(9/L and the presence of bleeding, the overall correct classification was 98%. The time course analysis supported platelet count as the key distinguishing variable. INTERPRETATION: There is substantial overlap in clinical presentation between dengue and chikungunya infections, but simple clinical and laboratory variables can predict these infections at presentation for appropriate management.

  4. Sources of Dengue Viruses Imported into Queensland, Australia, 2002–2010

    OpenAIRE

    Warrilow, David; Judith A Northill; Alyssa T. Pyke

    2012-01-01

    To assess risk for importation of dengue virus (DENV) into Queensland, Australia, and sources of imported viruses, we sequenced the envelope region of DENV isolates from symptomatic patients with a history of travel during 2002–2010. The number of imported dengue cases greatly increased over the surveillance period, some of which were associated with domestic outbreaks. Patients reported traveling to (in order) Asia, Papua New Guinea, Pacific Island countries, and non–Asia-Pacific countries. ...

  5. Epidemiological survey on chikungunya fever outbreak in Yangjiang city%阳江市一起基孔肯雅热暴发疫情流行病学调查

    Institute of Scientific and Technical Information of China (English)

    陈星红; 钟豪杰; 李文杰; 曾广富; 苏珊

    2012-01-01

    negative. Antibody of the IgG isotype was not found. Blood samples from five patients were checked for the viral nucleic acid and all the samples showed negative result for the dengue virus nucleic acid. However, two samples were found positive for the chikungunya fever virus nucleic acid. Conclusion There is an outbreak of chikungunya fever. Strengthening of the migration and quarantine of the migrants, carrying out symptom monitoring and controlling the vectors of the virus are important in the prevention and control of chikungunya.

  6. Tissue and host tropism of influenza viruses:Importance of quantitative analysis

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    It is generally accepted that human influenza viruses preferentially bind to cell-surface glycoproteins/ glycolipids containing sialic acids in α2,6-linkage; while avian and equine influenza viruses preferentially bind to those containing sialic acids in α2,3-linkage. Even though this generalized view is accurate for H3 subtype isolates, it may not be accurate and absolute for all subtypes of influenza A viruses and, therefore, needs to be reevaluated carefully and realistically. Some of the studies published in major scientific journals on the subject of tissue tropism of influenza viruses are inconsistent and caused confusion in the scientific community. One of the reasons for the inconsistency is that most studies were quantitative descriptions of sialic acid receptor distributions based on lectin or influenza virus immunohistochemistry results with limited numbers of stained cells. In addition, recent studies indicate that α2,3- and α2,6-linked sialic acids are not the sole receptors determining tissue and host tropism of influenza viruses. In fact, determinants for tissue and host tropism of human, avian and animal influenza viruses are more complex than what has been generally accepted. Other factors, such as glycan topology, concentration of invading viruses, local density of receptors, lipid raft microdomains, coreceptors or sialic acid-independent receptors, may also be important. To more efficiently control the global spread of pandemic influenza such as the current circulating influenza A H1N1, it is crucial to clarify the determinants for tissue and host tropism of influenza viruses through quantitative analysis of experimental results. In this review, I will comment on some conflicting issues related to tissue and host tropism of influenza viruses, discuss the importance of quantitative analysis of lectin and influenza virus immunohistochemistry results and point out directions for future studies in this area, which should lead to a better

  7. The Epidemic Trend and Control Strategies of Chikungunya Fever%基孔肯雅热的流行现况及其防治对策

    Institute of Scientific and Technical Information of China (English)

    刘春芳; 司菡; 陆家海

    2009-01-01

    基孔肯雅热(Chikungunya fever,CHIK)是由基孔肯雅病毒(chikungunya virus,CHIKV)引起的一种急性传染病.本文针对基孔肯雅热的病原学、流行现况、诊断方法、防治对策等方面做一综述.

  8. Comparitive evaluation of different systems of medicines and the present scenario of chikungunya in Kerala

    Institute of Scientific and Technical Information of China (English)

    Dilip C; Saraswathi R; Krishnan PN; AK Azeem; Raseena; Abdul azeez; Ramya; Jaywin jose

    2010-01-01

    Objective:To identify the chikungunya outbreaks in both indoor and outdoor patients in some selected hospitals in our locality and the burden and magnitude of the disease, to compare different system of medicines (allopathic, Ayurvedic, homeopathy etc) and to explore the knowledge, attitude and practices of pharmacists and other health care professionals in the treatment of chikungunya. Methods:A six-month study was carried out. Detailed history was taken from the case history, personal interview of doctors and suspected cases. Personal data such as name age, sex, location, date of onset of illness, medical history, general/systemic examination features, drugs used (allopathy, Ayurveda, homeopathy, or traditional) for the treatment, etc. were noted down. A simple questionnaire was prepared and distributed to various doctors practicing various systems of medicines. Results:A total of 209 suspected cases were identified from July to December, 2009. People in the age group of 20-40 years were more affected. The study revealed that females were more affected than males. The Grade-III (58.73%) population was more prone to chikungunya than Grade-II (38.75%) and Grade-I (2.87%). It showed that fever, pain in muscles, and sleeping disturbances were the intense symptoms of chikungunya. Myocarditis and arthritis were concomitant diseases which worsened chikungunya symptoms. It also indicated the effective medicine for compliance is nonsteroidal antiinflammatory drugs (NSAIDS). Conclusions:From our study we found that in some places there is no proper documentation, even though there are proper guidelines framed by the relevant authorities. It can be concluded from the study that all the systems of medicine are equally important for the management of chikungunya. Additional effort in promoting the guidelines at local level and proper documentation helps to achieve the goal of curbing the chikungunya. It is high time to increase our effort and promote these messages at

  9. Chikungunya triggers an autophagic process which promotes viral replication

    Directory of Open Access Journals (Sweden)

    Briant Laurence

    2011-09-01

    Full Text Available Abstract Background Chikungunya Virus (ChikV surprised by a massive re-emerging outbreak in Indian Ocean in 2006, reaching Europe in 2007 and exhibited exceptional severe physiopathology in infants and elderly patients. In this context, it is important to analyze the innate immune host responses triggered against ChikV. Autophagy has been shown to be an important component of the innate immune response and is involved in host defense elimination of different pathogens. However, the autophagic process was recently observed to be hijacked by virus for their own replication. Here we provide the first evidence that hallmarks of autophagy are specifically found in HEK.293 infected cells and are involved in ChikV replication. Methods To test the capacity of ChikV to mobilize the autophagic machinery, we performed fluorescence microscopy experiments on HEK.GFP.LC3 stable cells, and followed the LC3 distribution during the time course of ChikV infection. To confirm this, we performed electron microscopy on HEK.293 infected cells. To test the effect of ChikV-induced-autophagy on viral replication, we blocked the autophagic process, either by pharmacological (3-MA or genetic inhibition (siRNA against the transcript of Beclin 1, an autophagic protein, and analyzed the percentage of infected cells and the viral RNA load released in the supernatant. Moreover, the effect of induction of autophagy by Rapamycin on viral replication was tested. Results The increasing number of GFP-LC3 positive cells with a punctate staining together with the enhanced number of GFP-LC3 dots per cell showed that ChikV triggered an autophagic process in HEK.293 infected cells. Those results were confirmed by electron microscopy analysis since numerous membrane-bound vacuoles characteristic of autophagosomes were observed in infected cells. Moreover, we found that inhibition of autophagy, either by biochemical reagent and RNA interference, dramatically decreases ChikV replication

  10. [Chikungunya fever--expanded distribution of a re-emerging tropical infectious disease].

    Science.gov (United States)

    Stock, Ingo

    2009-01-01

    Chikungunya fever has been originally distributed in several parts of Africa, South Asia and Southeast Asia. The disease is caused by Chikungunya virus, an enveloped, single-stranded ribonucleic acid virus of the alphavirus genus (family Togaviridae). In Asia, virus transmission to humans occurs predominantly by the bite of the female Aedes aegypti or Aedes albopictus mosquito. In rural Africa, other mosquito species are also implicated in virus transmission. Chikungunya fever is characterized by fever with sudden onset, headache, backache, myalgia, and rash as well as painful and long-lasting arthralgia, affecting primarily the peripheral joints. Joint pain frequently persists for two or more months. Treatment strategies are primarily supportive and symptomatic and comprise the continuous application of certain analgetics, i.e., paracetamol (acetaminophen) and several non-steroidal anti-inflammatory agents. Although there is no generally recommended specific antiviral therapy, the use of chloroquine, ribavirin and interferon-alpha might be useful. In 2005 and 2006, the largest epidemic of Chikungunya fever ever recorded has been occurred in the islands of the southwest Indian Ocean and in India. The epidemic affected at least 1.3 million cases in India alone. The most affected island was the French territory La Réunion, where approximately one third of the total population (266,000 of 770,000) suffered from the disease. Based on the extent of the epidemic and the busy tourism between India/the islands of the Indian Ocean and Europe, numerous cases have been reported in several European countries since 2005. In 2007, one of these travellers served as "index patient" for the first outbreak of Chikungunya fever in a temperate region. Between July and September 2007, more than 200 cases of infection with Chikungunya virus have been notified in a region of north eastern Italy. The first autochthonic outbreak in Europe has been associated with the presence of A

  11. Chikungunya fever: a re-emerging viral infection.

    Science.gov (United States)

    Chhabra, M; Mittal, V; Bhattacharya, D; Rana, Uvs; Lal, S

    2008-01-01

    Chikungunya (CHIK) fever is a re-emerging viral disease characterized by abrupt onset of fever with severe arthralgia followed by constitutional symptoms and rash lasting for 1-7 days. The disease is almost self-limiting and rarely fatal. Chikungunya virus (CHIKV) is a RNA virus belonging to family Togaviridae, genus Alphavirus. Molecular characterization has demonstrated two distinct lineages of strains which cause epidemics in Africa and Asia. These geographical genotypes exhibit differences in the transmission cycles. In contrast to Africa where sylvatic cycle is maintained between monkeys and wild mosquitoes, in Asia the cycle continues between humans and the Aedes aegypti mosquito. CHIKV is known to cause epidemics after a period of quiescence. The first recorded epidemic occurred in Tanzania in 1952-1953. In Asia, CHIK activity was documented since its isolation in Bangkok, Thailand in 1958. Virus transmission continued till 1964. After hiatus, the virus activity re-appeared in the mid-1970s and declined by 1976. In India, well-documented outbreaks occurred in 1963 and 1964 in Kolkata and southern India, respectively. Thereafter, a small outbreak of CHIK was reported from Sholapur district, Maharashtra in 1973. CHIKV emerged in the islands of South West Indian Ocean viz. French island of La Reunion, Mayotee, Mauritius and Seychelles which are reporting the outbreak since February, 2005. After quiescence of about three decades, CHIKV re-emerged in India in the states of Andhra Pradesh, Karnataka, Maharashtra, Madhya Pradesh and Tamil Nadu since December, 2005. Cases have also been reported from Rajasthan, Gujarat and Kerala. The outbreak is still continuing. National Institute of Communicable Diseases has conducted epidemiological, entomological and laboratory investigations for confirmation of the outbreak. These have been discussed in detail along with the major challenges that the country faced during the current outbreak. PMID:18227590

  12. Chikungunya fever: A re-emerging viral infection

    Directory of Open Access Journals (Sweden)

    Chhabra M

    2008-01-01

    Full Text Available Chikungunya (CHIK fever is a re-emerging viral disease characterized by abrupt onset of fever with severe arthralgia followed by constitutional symptoms and rash lasting for 1-7 days. The disease is almost self-limiting and rarely fatal. Chikungunya virus (CHIKV is a RNA virus belonging to family Togaviridae, genus Alphavirus. Molecular characterization has demonstrated two distinct lineages of strains which cause epidemics in Africa and Asia. These geographical genotypes exhibit differences in the transmission cycles. In contrast to Africa where sylvatic cycle is maintained between monkeys and wild mosquitoes, in Asia the cycle continues between humans and the Aedes aegypti mosquito. CHIKV is known to cause epidemics after a period of quiescence. The first recorded epidemic occurred in Tanzania in 1952-1953. In Asia, CHIK activity was documented since its isolation in Bangkok, Thailand in 1958. Virus transmission continued till 1964. After hiatus, the virus activity re-appeared in the mid-1970s and declined by 1976. In India, well-documented outbreaks occurred in 1963 and 1964 in Kolkata and southern India, respectively. Thereafter, a small outbreak of CHIK was reported from Sholapur district, Maharashtra in 1973. CHIKV emerged in the islands of South West Indian Ocean viz. French island of La Reunion, Mayotee, Mauritius and Seychelles which are reporting the outbreak since February, 2005. After quiescence of about three decades, CHIKV re-emerged in India in the states of Andhra Pradesh, Karnataka, Maharashtra, Madhya Pradesh and Tamil Nadu since December, 2005. Cases have also been reported from Rajasthan, Gujarat and Kerala. The outbreak is still continuing. National Institute of Communicable Diseases has conducted epidemiological, entomological and laboratory investigations for confirmation of the outbreak. These have been discussed in detail along with the major challenges that the country faced during the current outbreak.

  13. Entomo-epidemiological investigations of chikungunya outbreak in Delhi, India

    Directory of Open Access Journals (Sweden)

    Ruchi Jain

    2013-01-01

    Full Text Available Context: An outbreak of fever with severe joint pain started in the Palam area of Delhi in August 2010. An entomological and epidemiological investigation of this outbreak was conducted to ascertain the nature and cause of the outbreak. Aim: Aim of the study was to investigate the nature and cause of the outbreak and to contain its further spread. Settings and Design: It was a cross-sectional study conducted in the Palam area of south-west Delhi, situated at a distance of about 20 km from Medical College. It is one of the field practice areas for training of undergraduate and postgraduate students of Department of Community Medicine of Medical College of Delhi. Materials and Methods: All patients attending OPD of Primary Health Center (PHC Palam, complaining of ever with incapacitating joint pain, were screened for chikungunya fever. Of the 750 suspected chikungunya patients, 130 blood samples were randomly drawn amongst these patients. Out of the 130 tested, 97 (70.8% were positive for the IgM antibodies against chikungunya virus. House-to-house survey was conducted in the affected area for more cases and to find out the vector-breeding sites. Statistical Analysis: Frequency distributions were calculated for age and sex. Results: The main breeding sites of the mosquitoes were the desert coolers of houses, water stored in metal and plastic containers, and water collections at construction sites. Aedes mosquito was present in almost all the houses surveyed in the area. Conclusions: It was concluded that the routine campaigns need to be organized regularly within the community highlighting the potential breeding grounds of mosquitoes and the possible control methods. Source reduction strategies like cleaning of desert coolers on weekly basis, emptying of water containers, and close monitoring of construction sites for potential breeding of the vector needs to be done on a regular basis to avoid future outbreaks.

  14. Isolation and characterization of Solenopsis invicta virus 3, a new positive-strand RNA virus infecting the red imported fire ant, Solenopsis invicta

    Science.gov (United States)

    We report the discovery of a new virus from the red imported fire ant, Solenopsis invicta. Solenopsis invicta virus 3 (SINV-3) represents the third virus identified from this ant species using the metagenomics approach. The single (positive)-strand RNA, monopartite, bicistronic genome of SINV-3 wa...

  15. Disease mapping based on stochastic SIR-SI model for Dengue and Chikungunya in Malaysia

    International Nuclear Information System (INIS)

    This paper describes and demonstrates a method for relative risk estimation which is based on the stochastic SIR-SI vector-borne infectious disease transmission model specifically for Dengue and Chikungunya diseases in Malaysia. Firstly, the common compartmental model for vector-borne infectious disease transmission called the SIR-SI model (susceptible-infective-recovered for human populations; susceptible-infective for vector populations) is presented. This is followed by the explanations on the stochastic SIR-SI model which involve the Bayesian description. This stochastic model then is used in the relative risk formulation in order to obtain the posterior relative risk estimation. Then, this relative estimation model is demonstrated using Dengue and Chikungunya data of Malaysia. The viruses of these diseases are transmitted by the same type of female vector mosquito named Aedes Aegypti and Aedes Albopictus. Finally, the findings of the analysis of relative risk estimation for both Dengue and Chikungunya diseases are presented, compared and displayed in graphs and maps. The distribution from risk maps show the high and low risk area of Dengue and Chikungunya diseases occurrence. This map can be used as a tool for the prevention and control strategies for both diseases

  16. Disease mapping based on stochastic SIR-SI model for Dengue and Chikungunya in Malaysia

    Science.gov (United States)

    Samat, N. A.; Ma'arof, S. H. Mohd Imam

    2014-12-01

    This paper describes and demonstrates a method for relative risk estimation which is based on the stochastic SIR-SI vector-borne infectious disease transmission model specifically for Dengue and Chikungunya diseases in Malaysia. Firstly, the common compartmental model for vector-borne infectious disease transmission called the SIR-SI model (susceptible-infective-recovered for human populations; susceptible-infective for vector populations) is presented. This is followed by the explanations on the stochastic SIR-SI model which involve the Bayesian description. This stochastic model then is used in the relative risk formulation in order to obtain the posterior relative risk estimation. Then, this relative estimation model is demonstrated using Dengue and Chikungunya data of Malaysia. The viruses of these diseases are transmitted by the same type of female vector mosquito named Aedes Aegypti and Aedes Albopictus. Finally, the findings of the analysis of relative risk estimation for both Dengue and Chikungunya diseases are presented, compared and displayed in graphs and maps. The distribution from risk maps show the high and low risk area of Dengue and Chikungunya diseases occurrence. This map can be used as a tool for the prevention and control strategies for both diseases.

  17. Disease mapping based on stochastic SIR-SI model for Dengue and Chikungunya in Malaysia

    Energy Technology Data Exchange (ETDEWEB)

    Samat, N. A.; Ma' arof, S. H. Mohd Imam [Department of Mathematics, Faculty of Science and Mathematics, Universiti Pendidikan Sultan Idris, 35900 Tanjung Malim, Perak (Malaysia)

    2014-12-04

    This paper describes and demonstrates a method for relative risk estimation which is based on the stochastic SIR-SI vector-borne infectious disease transmission model specifically for Dengue and Chikungunya diseases in Malaysia. Firstly, the common compartmental model for vector-borne infectious disease transmission called the SIR-SI model (susceptible-infective-recovered for human populations; susceptible-infective for vector populations) is presented. This is followed by the explanations on the stochastic SIR-SI model which involve the Bayesian description. This stochastic model then is used in the relative risk formulation in order to obtain the posterior relative risk estimation. Then, this relative estimation model is demonstrated using Dengue and Chikungunya data of Malaysia. The viruses of these diseases are transmitted by the same type of female vector mosquito named Aedes Aegypti and Aedes Albopictus. Finally, the findings of the analysis of relative risk estimation for both Dengue and Chikungunya diseases are presented, compared and displayed in graphs and maps. The distribution from risk maps show the high and low risk area of Dengue and Chikungunya diseases occurrence. This map can be used as a tool for the prevention and control strategies for both diseases.

  18. Dengue and Chikungunya Fever among Viral Diseases in Outpatient Febrile Children in Kilosa District Hospital, Tanzania

    OpenAIRE

    Beatrice Chipwaza; Joseph P Mugasa; Majige Selemani; Mbaraka Amuri; Fausta Mosha; Ngatunga, Steve D.; Gwakisa, Paul S.

    2014-01-01

    Introduction Viral etiologies of fever, including dengue, Chikungunya, influenza, rota and adeno viruses, cause major disease burden in tropical and subtropical countries. The lack of diagnostic facilities in developing countries leads to failure to estimate the true burden of such illnesses, and generally the diseases are underreported. These diseases may have similar symptoms with other causes of acute febrile illnesses including malaria and hence clinical diagnosis without laboratory tests...

  19. The role of environmental variables on Aedes albopictus biology and chikungunya epidemiology

    OpenAIRE

    Waldock, Joanna; Chandra, Nastassya L.; Lelieveld, Jos; Proestos, Yiannis; Michael, Edwin; Christophides, George; Parham, Paul E

    2013-01-01

    Aedes albopictus is a vector of dengue and chikungunya viruses in the field, along with around 24 additional arboviruses under laboratory conditions. As an invasive mosquito species, Ae. albopictus has been expanding in geographical range over the past 20 years, although the poleward extent of mosquito populations is limited by winter temperatures. Nonetheless, population densities depend on environmental conditions and since global climate change projections indicate increasing temperatures ...

  20. First report of sandfly fever virus infection imported from Malta into Switzerland, October 2011

    OpenAIRE

    Schultze, Detlev; W. Korte; Rafeiner, P.; Niedrig, Matthias

    2012-01-01

    We report the first documented cases of sandfly fever virus infection in travellers returning from Malta to Switzerland in autumn 2011. These cases illustrate the importance of considering sandfly-borne viral infection in the differential diagnosis of febrile patients from the Mediterranean island Malta. Raising awareness among physicians is relevant especially now at the beginning of the summer tourist season.

  1. First report of sandfly fever virus infection imported from Malta into Switzerland, October 2011.

    Science.gov (United States)

    Schultze, D; Korte, W; Rafeiner, P; Niedrig, M

    2012-07-05

    We report the first documented cases of sandfly fever virus infection in travellers returning from Malta to Switzerland in autumn 2011. These cases illustrate the importance of considering sandfly-borne viral infection in the differential diagnosis of febrile patients from the Mediterranean island Malta. Raising awareness among physicians is relevant especially now at the beginning of the summer tourist season.

  2. Autochthonous dengue virus infection in Japan imported into Germany, September 2013.

    Science.gov (United States)

    Schmidt-Chanasit, J; Emmerich, P; Tappe, D; Gunther, S; Schmidt, S; Wolff, D; Hentschel, K; Sagebiel, D; Schoneberg, I; Stark, K; Frank, C

    2014-01-01

    In September 2013, dengue virus (DENV) infection was diagnosed in a German traveller returning from Japan. DENV-specific IgM and IgG and DENV NS1 antigen were detected in the patient’s blood, as were DENV serotype 2-specific antibodies. Public health authorities should be aware that autochthonous transmission of this emerging virus may occur in Japan. Our findings also highlight the importance of taking a full travel history, even from travellers not returning from tropical countries, to assess potential infection risks of patients. PMID:24480059

  3. Autochthonous dengue virus infection in Japan imported into Germany, September 2013

    OpenAIRE

    Schmidt-Chanasit, Jonas; Emmerich, Petra; Tappe, D; Günther, Stephan; Schmidt, S.; Wolff, D; Hentschel, K.; Sagebiel, Daniel; Schöneberg, Irene; Stark, Klaus; Frank, Christina

    2014-01-01

    In September 2013, dengue virus (DENV) infection was diagnosed in a German traveller returning from Japan. DENV-specific IgM and IgG and DENV NS1 antigen were detected in the patient’s blood, as were DENV serotype 2-specific antibodies. Public health authorities should be aware that autochthonous transmission of this emerging virus may occur in Japan. Our findings also highlight the importance of taking a full travel history, even from travellers not returning from tropical countries, to asse...

  4. Positive-Strand RNA Viruses Infecting the Red Imported Fire Ant, Solenopsis invicta

    Directory of Open Access Journals (Sweden)

    Steven M. Valles

    2012-01-01

    Full Text Available The imported fire ants, Solenopsis invicta and S. richteri were introduced into the USA between 1918 and 1945. Since that time, they have expanded their USA range to include some 138 million hectares. Their introduction has had significant economic consequences with costs associated with damage and control efforts estimated at 6 billion dollars annually in the USA. The general consensus of entomologists and myrmecologists is that permanent, sustainable control of these ants in the USA will likely depend on self-sustaining biological control agents. A metagenomics approach successfully resulted in discovery of three viruses infecting S. invicta. Solenopsis invicta virus 1 (SINV-1, SINV-2, and SINV-3 are all positive, single-stranded RNA viruses and represent the first viral discoveries in any ant species. Molecular characterization, host relationships, and potential development and use of SINV-1, SINV-2, and SINV-3 as biopesticides are discussed.

  5. How Important is Vertical Transmission of Dengue Viruses by Mosquitoes (Diptera: Culicidae)?

    Science.gov (United States)

    Grunnill, Martin; Boots, Michael

    2016-01-01

    Vertical transmission of dengue viruses by mosquitoes was discovered at the end of the late 1970s and has been suggested to be a means by which these viruses persist. However, it is unclear how widespread it is in nature, and its importance in the epidemiology of this disease is still debated. Here, we review the literature on vertical transmission and discuss its role in dengue's epidemiology and control. We conclude that given the number of studies that failed to find evidence of vertical transmission, as well as mathematical models and its mechanistic basis, it is unlikely that vertical transmission is important for the epidemiological persistence of dengue viruses. A combination of asymptomatic infection in humans and movement of people are likely to be more important determinants of dengue's persistence. We argue, however, that there may be some need for further research into the prevalence of dengue viruses in desiccated, as well as diapausing, eggs and the role of horizontal transmission through larval cannibalism.

  6. How Important is Vertical Transmission of Dengue Viruses by Mosquitoes (Diptera: Culicidae)?

    Science.gov (United States)

    Grunnill, Martin; Boots, Michael

    2016-01-01

    Vertical transmission of dengue viruses by mosquitoes was discovered at the end of the late 1970s and has been suggested to be a means by which these viruses persist. However, it is unclear how widespread it is in nature, and its importance in the epidemiology of this disease is still debated. Here, we review the literature on vertical transmission and discuss its role in dengue's epidemiology and control. We conclude that given the number of studies that failed to find evidence of vertical transmission, as well as mathematical models and its mechanistic basis, it is unlikely that vertical transmission is important for the epidemiological persistence of dengue viruses. A combination of asymptomatic infection in humans and movement of people are likely to be more important determinants of dengue's persistence. We argue, however, that there may be some need for further research into the prevalence of dengue viruses in desiccated, as well as diapausing, eggs and the role of horizontal transmission through larval cannibalism. PMID:26545718

  7. Are viruses important in the plankton of highly turbid glacier-fed lakes?

    Science.gov (United States)

    Drewes, Fabian; Peter, Hannes; Sommaruga, Ruben

    2016-01-01

    Viruses are ubiquitous in aquatic ecosystems where they significantly contribute to microbial mortality. In glacier-fed turbid lakes, however, viruses not only encounter low host abundances, but also a high number of suspended mineral particles introduced by glacier meltwaters. We hypothesized that these particles potentially lead to unspecific adsorption and removal of free virus from the plankton, and thus significantly reduce their abundance in this type of lake. We followed the distribution of free virus-like particles (VLP) during the ice-free season across a turbidity gradient in four alpine lakes including one adjacent clear system where hydrological connectivity to the receding glacier is already lost. In the glacier-fed turbid lakes, VLP abundance increased with distance to the glacier, but the highest numbers were observed in the clear lake by the end of August, coinciding with the maximum in prokaryotic abundance. Our results suggest that viral loss by attachment to particles is less important than expected. Nevertheless, the relatively lower variability in VLP abundance and the lower virus-to-prokaryote ratio found in the turbid lakes than in the clear one point to a rather low temporal turnover and thus, to a reduced impact on microbial communities. PMID:27094854

  8. Evaluation of Chikungunya diagnostic assays: differences in sensitivity of serology assays in two independent outbreaks.

    Directory of Open Access Journals (Sweden)

    Grace Yap

    Full Text Available BACKGROUND: The sensitivity and specificity of two in-house MAC-ELISA assays were tested and compared with the performance of commercially-available CTK lateral flow rapid test and EUROIMMUN IFA assays for the detection of anti-Chikungunya virus (CHIKV IgM. Each MAC-ELISA assay used a whole virus-based antigen derived from genetically distinct CHIKV strains involved in two chikungunya disease outbreaks in Singapore (2008; a January outbreak strain with alanine at amino acid residue 226 of the E1 glycoprotein (CHIKV-A226 and a May-to-September outbreak strain that possessed valine at the same residue (CHIKV-226V. We report differences in IgM detection efficacy of different assays between the two outbreaks. The sensitivities of two PCR protocols were also tested. METHODS AND FINDINGS: For sera from January outbreak, the average detection threshold of CTK lateral flow test, MAC-ELISAs and EUROIMMUN IFA assays was 3.75, 4.38 and 4.88 days post fever onset respectively. In contrast, IgM detection using CTK lateral flow test was delayed to more than 7 days after fever onset in the second outbreak sera. However, MAC-ELISA using CHIKV-226V detected IgM in the second outbreak sera 3.96 days after fever onset, which was approximately one day earlier compared to the same assay using CHIKV-A226 (4.86 days. Specificity was 100% for both commercial assays, and 95.6% for the in-house MAC-ELISAs. For sensitivity determination of the PCR protocols, the probe-based real time RT-PCR method was found to be 10 times more sensitive than one based on SYBR Green. CONCLUSION: Our findings suggested that the two strains of CHIKV using variants A226 and 226V resulted in variation in sensitivities of the assays evaluated. We postulated that the observed difference in antigen efficacy could be due to the amino acid substitution differences in viral E1 and E2 envelope proteins, especially the E1-A226V substitution. This evaluation demonstrates the importance of appraisal of

  9. 'ANOTHER VECTOR BORNE CHALLENGE TO COMBAT- ZIKA VIRUS OUTBREAKS'.

    Science.gov (United States)

    Shoaib, Maria; Faraz, Ahmad; Ahmed, Syed Ahsanuddin

    2016-01-01

    Zika virus is a single-stranded RNA virus of the Flaviviridae family. It is known to transmit to humans primarily through the bite of an infected Aedes species mosquito which is also known to carry dengue, chikungunya & yellow fever virus. Transmission is anthroponotic (human-to-vector-to-human) during outbreaks, Perinatally in utero, sexually and via infected blood transfusion. It is mild and self-limiting infection lasting for several days to a week. However, it is suspected as a cause of Guillain Barre Syndrome. There is a teratogenic association of Zika virus causing congenital birth defects like microcephaly and neurologic abnormalities. Treatment is generally supportive and for symptomatic relief. No specific antiviral treatment or vaccine is yet available for Zika virus disease. It highlights importance of preventive public health measures at the community level and avoids travelling to the endemic areas. PMID:27323600

  10. Acquired auditory neuropathy spectrum disorder after an attack of chikungunya: case study.

    Science.gov (United States)

    Prabhu, Prashanth

    2016-01-01

    Auditory neuropathy spectrum disorder (ANSD) is a retrocochlear disorder in which the cochlear functioning is normal but the transmission in the auditory neural pathway is affected. The present study reports of a 14-year-old teenager with acquired ANSD after an attack of chikungunya. He reported symptoms of difficulty in understanding speech, tinnitus and vertigo when exposed to loud sounds. The audiological characteristics suggested auditory neuropathy spectrum disorder with raising audiogram configuration. The results of tinnitus evaluation showed low-pitched tinnitus and it was persistent causing significant handicap to him based on self report tinnitus handicap questionnaire results. The results of depression, anxiety and stress scale also suggested symptoms of mild depression and anxiety. Chikungunya virus is suspected to be neurotropic in nature which can damage auditory nerve cells and may have caused ANSD. The result also shows presence of tullio's phenomenon and absence of cervical vestibular evoked myogenic potentials suggesting damage to the vestibular neuronal system. The possible pathophysiology of chikungunya virus causing ANSD and vestibular symptoms needs to be explored further in future studies. PMID:25728940

  11. Waiting for chikungunya fever in Argentina: spatio-temporal risk maps

    Directory of Open Access Journals (Sweden)

    Aníbal E Carbajo

    2015-04-01

    Full Text Available Chikungunya virus (CHIKV transmission has been detected in America in 2013 and recently reached south up to Bolivia, Brazil and Paraguay, bordering countries of Argentina. The presence of the mosquito Aedes aegypti in half of the country together with the regional context drove us to make a rapid assessment of transmission risk. Temperature thresholds for vector breeding and for virus transmission, together with adult activity from the literature, were mapped on a monthly basis to estimate risk. Transmission of chikungunya by Ae. aegypti in the world was seen at monthly mean temperatures from 21-34ºC, with the majority occurring between 26-28ºC. In Argentina temperatures above 21ºC are observed since September in the northeast, expanding south until January and retreating back to the northeast in April. The maximum area under risk encompasses more than half the country and around 32 million inhabitants. Vector adult activity was registered where monthly means temperatures exceeded 13ºC, in the northeast all over the year and in the northern half from September-May. The models herein proposed show that conditions for transmission are already present. Considering the regional context and the historic inability to control dengue in the region, chikungunya fever illness seems unavoidable.

  12. Chikungunya fever in the Emilia Romagna region: what is the public health message?

    Directory of Open Access Journals (Sweden)

    Giuseppe La Torre

    2009-03-01

    Full Text Available

    Introduction Chikungunya virus (CHIKV is a mosquitoborne alphavirus indigenous to African countries, the Indian Subcontinent, and Southeast Asia, where it causes endemic and epidemic chikungunya (CHIK fever [1]. Chikungunya infection is transmitted by biting mosquitoes belonging to the genus Aedes. Since the identification of the virus in the 1950s [2] in Africa, transmission to humans has been usually associated with bites of A. aegypti mosquitoes. In recent outbreaks occurring in the South-eastern islands of the Indian Ocean, transmission has also been associated with A. albopictus, also known as the “tiger mosquito.” This species is indigenous to Southeast Asia, the Western Pacific, and the Indian Ocean, but has recently spread to Africa, the Middle East, Europe, and the Americas. [3]. Although tropical forests are considered to be their original habitat, A. aegypti and A. albopictus have developed the capacity to exploit artificial environments [4]. Besides the natural habitat consisting of tree holes filled with water and other small natural pools, they are capable of breeding in any artificial habitat with small reservoirs of stagnant water, such as vases, buckets, tires and other containers found around houses in urban and periurban areas.

  13. A human genome-wide loss-of-function screen identifies effective chikungunya antiviral drugs

    Science.gov (United States)

    Karlas, Alexander; Berre, Stefano; Couderc, Thérèse; Varjak, Margus; Braun, Peter; Meyer, Michael; Gangneux, Nicolas; Karo-Astover, Liis; Weege, Friderike; Raftery, Martin; Schönrich, Günther; Klemm, Uwe; Wurzlbauer, Anne; Bracher, Franz; Merits, Andres; Meyer, Thomas F.; Lecuit, Marc

    2016-01-01

    Chikungunya virus (CHIKV) is a globally spreading alphavirus against which there is no commercially available vaccine or therapy. Here we use a genome-wide siRNA screen to identify 156 proviral and 41 antiviral host factors affecting CHIKV replication. We analyse the cellular pathways in which human proviral genes are involved and identify druggable targets. Twenty-one small-molecule inhibitors, some of which are FDA approved, targeting six proviral factors or pathways, have high antiviral activity in vitro, with low toxicity. Three identified inhibitors have prophylactic antiviral effects in mouse models of chikungunya infection. Two of them, the calmodulin inhibitor pimozide and the fatty acid synthesis inhibitor TOFA, have a therapeutic effect in vivo when combined. These results demonstrate the value of loss-of-function screening and pathway analysis for the rational identification of small molecules with therapeutic potential and pave the way for the development of new, host-directed, antiviral agents. PMID:27177310

  14. The First Reported Outbreak of Chikungunya in the U.S. Virgin Islands, 2014–2015

    Science.gov (United States)

    Feldstein, Leora R.; Ellis, Esther M.; Rowhani-Rahbar, Ali; Halloran, M. Elizabeth; Ellis, Brett R.

    2016-01-01

    The chikungunya virus (CHIKV) epidemic in the Americas is of significant public health importance due to the lack of effective control and prevention strategies, severe disease morbidity among susceptible populations, and potential for persistent arthralgia and long-term impaired physical functionality. Using surveillance data of suspected CHIKV cases, we describe the first reported outbreak in the U.S. Virgin Islands. CHIKV incidence was highest among individuals aged 55–64 years (13.1 cases per 1,000 population) and lowest among individuals aged 0–14 years (1.8 cases per 1,000 population). Incidence was higher among women compared to men (6.6 and 5.0 cases per 1,000 population, respectively). More than half of reported laboratory-positive cases experienced fever lasting 2–7 days, chills/rigor, myalgia, anorexia, and headache. No clinical symptoms apart from the suspected case definition of fever ≥ 38°C and arthralgia were significantly associated with being a reported laboratory-positive case. These results contribute to our knowledge of demographic risk factors and clinical manifestations of CHIKV disease and may aid in mitigating future CHIKV outbreaks in the Caribbean. PMID:27402523

  15. Retrospective survey of Chikungunya disease in Réunion Island hospital staff

    Science.gov (United States)

    STAIKOWSKY, F.; Le ROUX, K.; SCHUFFENECKER, I.; LAURENT, P.; GRIVARD, P.; DEVELAY, A.; MICHAULT, A.

    2008-01-01

    SUMMARY Réunion Island (Indian Ocean) has been suffering from its first known Chikungunya virus (CHIKV) epidemic since February 2005. To achieve a better understanding of the disease, a questionnaire was drawn up for hospital staff members and their household. CHIKV infected about one-third of the studied population, the proportion increasing with age and being higher in women. Presence of a garden was associated with CHIKV infection. The geographical distribution of cases was concordant with insect vector Aedes albopictus distribution. The main clinical signs were arthralgia and fever. The disease evolved towards full recovery in 34·4% of cases, a relapse in 55·6%, or a chronic form in 10%. Paracetamol was used as a painkiller in 95% of cases, sometimes associated with non-steroidal anti-inflammatory drugs, corticoids, or traditional herbal medicine. The survey provided valuable information on the factors that favour transmission, the clinical signs, the importance of relapses and the therapies used. PMID:17433130

  16. Replication cycle of chikungunya: a re-emerging arbovirus.

    Science.gov (United States)

    Solignat, Maxime; Gay, Bernard; Higgs, Stephen; Briant, Laurence; Devaux, Christian

    2009-10-25

    Arboviruses (or arthropod-borne viruses), represent a threat for the new century. The 2005-2006 year unprecedented epidemics of chikungunya virus (CHIKV) in the French Reunion Island in the Indian Ocean, followed by several outbreaks in other parts of the world such as India, have attracted the attention of clinicians, scientists, and state authorities about the risks linked to this re-emerging mosquito-borne virus. CHIKV, which belongs to the Alphaviruses genus, was not previously regarded as a highly pathogenic arbovirus. However, this opinion was challenged by the death of several CHIKV-infected persons in Reunion Island. The epidemic episode began in December 2005 and four months later the seroprevalence survey report indicated that 236,000 persons, more than 30% of Reunion Island population, had been infected with CHIKV, among which 0.4-0.5% of cases were fatal. Since the epidemic peak, the infection case number has continued to increase to almost 40% of the population, with a total of more than 250 fatalities. Although information available on CHIKV is growing quite rapidly, we are still far from understanding the strategies required for the ecologic success of this virus, virus replication, its interactions with its vertebrate hosts and arthropod vectors, and its genetic evolution. In this paper, we summarize the current knowledge of CHIKV genomic organization, cell tropism, and the virus replication cycle, and evaluate the possibility to predict its future evolution. Such understanding may be applied in order to anticipate future epidemics and reduce the incidence by development and application of, for example, vaccination and antiviral therapy. PMID:19732931

  17. Tracking oseltamivir-resistance in New Zealand influenza viruses during a medicine reclassification in 2007, a resistant-virus importation in 2008 and the 2009 pandemic

    Directory of Open Access Journals (Sweden)

    Q Sue Huang

    2012-10-01

    Full Text Available Introduction: Oseltamivir (Tamiflu® is an important pharmaceutical intervention against the influenza virus. The importance of surveillance for resistance to oseltamivir has been highlighted by two global events: the emergence of an oseltamivir-resistant seasonal influenza A(H1N1 virus in 2008, and emergence of the influenza A(H1N1pdm09 virus in 2009. Oseltamivir is a prescription medicine in New Zealand, but more timely access has been provided since 2007 by allowing pharmacies to directly dispense oseltamivir to patients with influenza-like illness.Objective: To determine the frequency of oseltamivir-resistance in the context of a medicine reclassification in 2007, the importation of an oseltamivir-resistant seasonal influenza virus in 2008, and the emergence of a pandemic in 2009.Methods: A total of 1795 influenza viruses were tested for oseltamivir-resistance using a fluorometric neuraminidase inhibition assay. Viruses were collected as part of a sentinel influenza surveillance programme between the years 2006 and 2010.Results: All influenza B, influenza A(H3N2 and influenza A(H1N1pdm09 viruses tested between 2006 and 2010 were shown to be sensitive to oseltamivir. Seasonal influenza A(H1N1 viruses from 2008 and 2009 were resistant to oseltamivir. Sequencing of the neuraminidase gene showed that the resistant viruses contained an H275Y mutation, and S247N was also identified in the neuraminidase gene of one seasonal influenza A(H1N1 virus that exhibited enhanced resistance.Discussion: No evidence was found to suggest that increased access to oseltamivir has promoted resistance. A probable importation event was documented for the global 2008 oseltamivir-resistant seasonal A(H1N1 virus nine months after it was first reported in Europe in January 2008.

  18. Importance of canine distemper virus (CDV) infection in free-ranging Iberian lynxes (Lynx pardinus)

    OpenAIRE

    Meli, Marina L; Simmler, P.; Cattori, Valentino; Martínez, Fernando; Vargas, Astrid; Palomares, Francisco; López-Bao, José V.; Miguel A. Simón; López, Guillermo; Hofmann-Lehmann, R.; Lutz, Hans

    2010-01-01

    Canine distemper virus (CDV) is a morbillivirus that is the etiological agent of one of the most important viral diseases affecting canids and an expanding range of other carnivores. Using real-time RT-PCR, CDV RNA was detected in organs of an Iberian lynx (Lynx pardinus) found dead in the Doñana National Park, Southwestern Andalusia, Spain. This finding may be of great importance for the conservation of the species; at present the Iberian lynx is the most critically endangered wild felid. Th...

  19. Chikungunya infection in India: results of a prospective hospital based multi-centric study.

    Directory of Open Access Journals (Sweden)

    Pratima Ray

    molecular diagnostic for early detection of chikungunya virus.

  20. Replication and clearance of respiratory syncytial virus - Apoptosis is an important pathway of virus clearance after experimental infection with bovine respiratory syncytial virus

    DEFF Research Database (Denmark)

    Viuff, B.; Tjørnehøj, Kirsten; Larsen, Lars Erik;

    2002-01-01

    and clearance in a natural target animal. Replication of BRSV was demonstrated in the luminal part of the respiratory epithelial cells and replication in the upper respiratory tract preceded the replication in the lower respiratory tract. Virus excreted to the lumen of the respiratory tract was cleared...... by neutrophils whereas apoptosis was an important way of clearance of BRSV-infected epithelial cells. Neighboring cells, which probably were epithelial cells, phagocytized the BRSV-infected apoptotic cells. The number of both CD4+ and CD8+ T cells increased during the course of infection, but the T cells were...

  1. Chikungunya fever: CNS infection and pathologies of a re-emerging arbovirus.

    Science.gov (United States)

    Das, Trina; Jaffar-Bandjee, Marie Christine; Hoarau, Jean Jacques; Krejbich Trotot, Pascale; Denizot, Melanie; Lee-Pat-Yuen, Ghislaine; Sahoo, Renubala; Guiraud, Pascale; Ramful, Duksha; Robin, Stephanie; Alessandri, Jean Luc; Gauzere, Bernard Alex; Gasque, Philippe

    2010-06-01

    Chikungunya virus (CHIKV) is transmitted by Aedes mosquitoes and causes an acute symptomatic illness with fever, skin rash, and incapacitating arthralgia, which can evolve into chronic rheumatoid arthritis in elderly patients. This is a tropical disease originally described in central/east Africa in the 1960s, but its 2004 re-emergence in Africa and rapid spread in lands in and around the Indian Ocean (Reunion island, India, Malaysia) as well as Europe (Italy) led to almost 6 million cases worldwide. The risk of importation and spreading diseases with long-term sequelae is even greater today given the global distribution of the vectors (including in the Americas), increased tourism and the apparent capacity of CHIKV to produce high levels of viremia (10(9)-10(12) virus/ml of blood) and new mutants. CHIKV-associated neuropathology was described early in the 1960s, but it is the unprecedented incidence rate in Indian Ocean areas with efficient clinical facilities that allowed a better description of cases with severe encephalitis, meningoencephalitis, peripheral neuropathies and deaths among newborns (mother-to-child infection), infants and elderly patients. Death rates following CHIKV infection were estimated at 1:1000 cases in la Reunion's outbreak. These clinical observations have been corroborated by experimental infection in several mouse models, leading to CNS pathologies. We further describe in this review the capacity of CHIKV to infect neurons and glial cells, delineate the fundamental innate (intrinsic) immune defence mechanisms to protect from infection and argue about the possible mechanisms involved in the encephalopathy. PMID:20026374

  2. Imported lassa fever in Germany: molecular characterization of a new lassa virus strain.

    OpenAIRE

    Günther, S.; Emmerich, P.; Laue, T.; Kühle, O.; Asper, M.; Jung, A.; Grewing, T.; ter Meulen, J; Schmitz, H.

    2000-01-01

    We describe the isolation and characterization of a new Lassa virus strain imported into Germany by a traveler who had visited Ghana, Côte D'Ivoire, and Burkina Faso. This strain, designated "AV," originated from a region in West Africa where Lassa fever has not been reported. Viral S RNA isolated from the patient's serum was amplified and sequenced. A long-range reverse transcription polymerase chain reaction allowed amplification of the full-length (3.4 kb) S RNA. The coding sequences of st...

  3. 云南基孔肯雅热研究概况%Current progress in research of Chikungunya fever in Yunnan Province in China

    Institute of Scientific and Technical Information of China (English)

    王艳红; 宝福凯; 柳爱华

    2013-01-01

    基孔肯雅热(Chikungunya fever,CHIK)是由基孔肯雅病毒(Chikungunya virus,CHIKV)引起的一种急性自然疫源性传染病,经伊蚊叮咬而传播.由于CHIK的分布与其传播媒介伊蚊的分布密切相关,因此云南具有引起本病流行的条件,是CHIK主要流行省份之一.本文拟对云南CHIK研究的历史和现状做一综述.

  4. Molecular confirmation of infectious spleen and kidney necrosis virus (ISKNV) in farmed and imported ornamental fish in Australia.

    Science.gov (United States)

    Mohr, Peter G; Moody, Nicholas J G; Williams, Lynette M; Hoad, John; Cummins, David M; Davies, Kelly R; StJ Crane, Mark

    2015-10-16

    Viruses of the genus Megalocytivirus have not been detected in wild populations of fish in Australia but circulate in imported ornamental fish. In 2012, detection of a megalocytivirus in healthy platys Xiphophorus maculatus was reported from a farm in Australia during surveillance testing as part of a research project undertaken at the University of Sydney. Confirmatory testing of the original samples at the AAHL Fish Diseases Laboratory verified the presence of an infectious spleen and kidney necrosis virus (ISKNV)-like virus. Additional sampling at the positive farm confirmed the persistence of the virus in the platys, with 39 of 265 (14.7%) samples testing positive. Comparison of 3 separate gene regions of the virus with those of ISKNV confirmed the detection of a virus indistinguishable from ISKNV. Subsequently, ISKNV was also detected in a range of imported ornamental fish from several countries between 2013 and 2014, by screening with real-time PCR and confirmation by conventional PCR and sequence analysis. Accordingly, the current importation of live ornamental fish acts as a potential perpetual source for the establishment of ISKNV viruses within Australia. The testing of the farmed and imported ornamental fish verified the utility of the probe-based real-time PCR assay for screening of ornamental fish for Megalocytivirus. PMID:26480913

  5. ISCB Ebola Award for Important Future Research on the Computational Biology of Ebola Virus.

    Directory of Open Access Journals (Sweden)

    Peter D. Karp

    2015-01-01

    Full Text Available Speed is of the essence in combating Ebola; thus, computational approaches should form a significant component of Ebola research. As for the development of any modern drug, computational biology is uniquely positioned to contribute through comparative analysis of the genome sequences of Ebola strains as well as 3-D protein modeling. Other computational approaches to Ebola may include large-scale docking studies of Ebola proteins with human proteins and with small-molecule libraries, computational modeling of the spread of the virus, computational mining of the Ebola literature, and creation of a curated Ebola database. Taken together, such computational efforts could significantly accelerate traditional scientific approaches. In recognition of the need for important and immediate solutions from the field of computational biology against Ebola, the International Society for Computational Biology (ISCB announces a prize for an important computational advance in fighting the Ebola virus. ISCB will confer the ISCB Fight against Ebola Award, along with a prize of US$2,000, at its July 2016 annual meeting (ISCB Intelligent Systems for Molecular Biology [ISMB] 2016, Orlando, Florida.

  6. Imported Genotype 2B Rubella Virus Caused the 2012 Outbreak in Anqing City, China.

    Directory of Open Access Journals (Sweden)

    Zhen Zhu

    Full Text Available A rubella outbreak occurred in Anqing city of Anhui province, China, from February to July of 2012, and a total of 241 clinically diagnosed or lab-confirmed patients were reported. The highest number of rubella cases during this outbreak was recorded in teenagers between 10 and 19 years of age who had not previously received the rubella vaccine. Genotyping results indicated that the genotype 2B rubella virus (RV was responsible for the outbreak. However, a phylogenetic analysis showed that the genotype 2B RVs isolated in Anqing City were not related to 2B RVs found in other cities of Anhui province and in other provinces of China, thus providing evidence for importation. After importation, the transmission of Anqing RVs was interrupted owing to an effective immunization campaign against rubella, suggesting the timeliness and effectiveness of contingency vaccination. Strengthening rubella surveillance, including the integration of epidemiologic information and laboratory data, is a vital strategy for rubella control and elimination. In addition, except for routine immunization, targeted supplementary immunization activities aimed at susceptible groups according to sero-epidemiological surveillance data also play a key role in stopping the continuous transmission of rubella viruses and in preventing further congenital rubella syndrome cases.

  7. External quality assessment of dengue and chikungunya diagnostics in the Asia Pacific region, 2015

    Directory of Open Access Journals (Sweden)

    Li Ting Soh

    2016-04-01

    Full Text Available Objective: To conduct an external quality assessment (EQA of dengue and chikungunya diagnostics among national-level public health laboratories in the Asia Pacific region following the first round of EQA for dengue diagnostics in 2013. Methods: Twenty-four national-level public health laboratories performed routine diagnostic assays on a proficiency testing panel consisting of two modules. Module A contained serum samples spiked with cultured dengue virus (DENV or chikungunya virus (CHIKV for the detection of nucleic acid and DENV non-structural protein 1 (NS1 antigen. Module B contained human serum samples for the detection of anti-DENV antibodies. Results: Among 20 laboratories testing Module A, 17 (85% correctly detected DENV RNA by reverse transcription polymerase chain reaction (RT-PCR, 18 (90% correctly determined serotype and 19 (95% correctly identified CHIKV by RT-PCR. Ten of 15 (66.7% laboratories performing NS1 antigen assays obtained the correct results. In Module B, 18/23 (78.3% and 20/20 (100% of laboratories correctly detected anti-DENV IgM and IgG, respectively. Detection of acute/recent DENV infection by both molecular (RT-PCR and serological methods (IgM was available in 19/24 (79.2% participating laboratories. Discussion: Accurate laboratory testing is a critical component of dengue and chikungunya surveillance and control. This second round of EQA reveals good proficiency in molecular and serological diagnostics of these diseases in the Asia Pacific region. Further comprehensive diagnostic testing, including testing for Zika virus, should comprise future iterations of the EQA.

  8. Production and characterization of mouse monoclonal antibodies reactive to Chikungunya envelope E2 glycoprotein.

    Science.gov (United States)

    Bréhin, Anne-Claire; Rubrecht, Laetitia; Navarro-Sanchez, Martha Erika; Maréchal, Valérie; Frenkiel, Marie-Pascale; Lapalud, Priscilla; Laune, Daniel; Sall, Amadou Alpha; Desprès, Philippe

    2008-02-01

    Chikungunya fever is an arbovirosis of major impact in public health in Asia and Africa. Chikungunya (CHIK) virus is member of the genus Alphavirus and belongs to the Semliki Forest (SF) antigenic complex. We describe for the first time a panel of monoclonal antibodies (MAbs) reactive to CHIK envelope E2 glycoprotein. For the screening of E2-specific MAbs, we expressed a recombinant soluble CHIK E2 protein in Drosophila S2 cells. Analyzed by immunological methods, MAbs 3C3, 3E4, and 8A4 were selected on the basis of their reactivity. Their epitopes are located to the outer surface of CHIK virion. These MAbs have no cross reactivity with related members of SF antigenic complex with the notable exception of Igbo-Ora virus. Anti-CHIK E2 MAbs 3C3, 3E4, and 8A4 should be helpful for studying the biology of CHIK virus and pathogenesis of disease. The combination of 8A4 and 3E4 is suitable for developing a specific antigen-capture ELISA. PMID:17949772

  9. Imported lassa fever in Germany: molecular characterization of a new lassa virus strain.

    Science.gov (United States)

    Günther, S.; Emmerich, P.; Laue, T.; Kühle, O.; Asper, M.; Jung, A.; Grewing, T.; ter Meulen, J.; Schmitz, H.

    2000-01-01

    We describe the isolation and characterization of a new Lassa virus strain imported into Germany by a traveler who had visited Ghana, Côte D'Ivoire, and Burkina Faso. This strain, designated "AV," originated from a region in West Africa where Lassa fever has not been reported. Viral S RNA isolated from the patient's serum was amplified and sequenced. A long-range reverse transcription polymerase chain reaction allowed amplification of the full-length (3.4 kb) S RNA. The coding sequences of strain AV differed from those of all known Lassa prototype strains (Josiah, Nigeria, and LP) by approximately 20%, mainly at third codon positions. Phylogenetically, strain AV appears to be most closely related to strain Josiah from Sierra Leone. Lassa viruses comprise a group of genetically highly diverse strains, which has implications for vaccine development. The new method for full-length S RNA amplification may facilitate identification and molecular analysis of new arenaviruses or arenavirus strains. PMID:10998376

  10. Zika virus infections imported to Italy: clinical, immunological and virological findings, and public health implications.

    Science.gov (United States)

    Zammarchi, Lorenzo; Stella, Giulia; Mantella, Antonia; Bartolozzi, Dario; Tappe, Dennis; Günther, Stephan; Oestereich, Lisa; Cadar, Daniel; Muñoz-Fontela, César; Bartoloni, Alessandro; Schmidt-Chanasit, Jonas

    2015-02-01

    We report the first two cases of laboratory confirmed Zika virus (ZIKV) infections imported into Italy from French Polynesia. Both patients presented with low grade fever, malaise, conjunctivitis, myalgia, arthralgia, ankle oedema, and axillary and inguinal lymphadenopathy. One patient showed leukopenia with relative monocytosis and thrombocytopenia. The diagnosis was based on ZIKV seroconversion in both cases and on ZIKV RNA detection in one patient from acute serum sample. Sera from both patients exhibited cross-reactivity with dengue virus antigens. Our immunological analysis demonstrated that recovery from ZIKV infection is associated with restoration of normal numbers of immune cells in the periphery as well as with normal function of antigen-presenting cells. ZIKV is an emerging arbovirus, which has recently spread extensively in tourist destinations on several West Pacific islands. Returning viremic travelers may ignite autochthonous infections in countries like Italy, which are infested by Aedes albopictus, a suitable vector for ZIKV. The role of clinicians is crucial and includes early diagnosis and timely notification of public health authorities in order to quickly implement adequate focal vector control measurements.

  11. Restrictions on the Importation of Zebrafish into Canada Associated with Spring Viremia of Carp Virus.

    Science.gov (United States)

    Hanwell, David; Hutchinson, Sarah A; Collymore, Chereen; Bruce, Ashley E; Louis, Rhain; Ghalami, Ayoob; Allison, W Ted; Ekker, Marc; Eames, B Frank; Childs, Sarah; Kurrasch, Deborah M; Gerlai, Robert; Thiele, Tod; Scott, Ian; Ciruna, Brian; Dowling, James J; McFarlane, Sarah; Huang, Peng; Wen, Xiao-Yan; Akimenko, Marie-Andrée; Waskiewicz, Andrew J; Drapeau, Pierre; Babiuk, Lorne A; Dragon, Dan; Smida, Andrea; Buret, Andre Gerald; O'Grady, Eoin; Wilson, Joanna; Sowden-Plunkett, Lois; Tropepe, Vincent

    2016-07-01

    The zebrafish model system is helping researchers improve the health and welfare of people and animals and has become indispensable for advancing biomedical research. As genetic engineering is both resource intensive and time-consuming, sharing successfully developed genetically modified zebrafish lines throughout the international community is critical to research efficiency and to maximizing the millions of dollars in research funding. New restrictions on importation of zebrafish into Canada based on putative susceptibility to infection by the spring viremia of carp virus (SVCV) have been imposed on the scientific community. In this commentary, we review the disease profile of SVCV in fish, discuss the findings of the Canadian government's scientific assessment, how the interpretations of their assessment differ from that of the Canadian research community, and describe the negative impact of these regulations on the Canadian research community and public as it pertains to protecting the health of Canadians. PMID:27248438

  12. Confirmed Zika virus infection in a Belgian traveler returning from Guatemala, and the diagnostic challenges of imported cases into Europe.

    Science.gov (United States)

    De Smet, Birgit; Van den Bossche, Dorien; van de Werve, Charlotte; Mairesse, Jacques; Schmidt-Chanasit, Jonas; Michiels, Jo; Ariën, Kevin K; Van Esbroeck, Marjan; Cnops, Lieselotte

    2016-07-01

    We report the first laboratory-confirmed Zika virus (ZIKV) infection in a Belgian traveler after a three week holiday in Guatemala, December 2015. This case along with other imported cases into Europe emphases once again the need for accurate diagnostic tools for this rapidly emerging virus. The challenge is to diagnose patients in the acute phase, which appears short, as serological testing is complicated by cross-reactivity, vaccination status and scarce availability of specific ZIKV tests.

  13. A picorna-like virus from the red imported fire ant, Solenopsis invicta: initial discovery, genome sequence, and characterization

    International Nuclear Information System (INIS)

    We report the first discovery and genome sequence of a virus infecting the red imported fire ant, Solenopsis invicta. The 8026 nucleotide, polyadenylated, RNA genome encoded two large open reading frames (ORF1 and ORF2), flanked and separated by 27, 223, and 171 nucleotide untranslated regions, respectively. The predicted amino acid sequence of the 5' proximal ORF1 (nucleotides 28 to 4218) exhibited significant identity and possessed consensus sequences characteristic of the helicase, cysteine protease, and RNA-dependent RNA polymerase sequence motifs from picornaviruses, picorna-like viruses, comoviruses, caliciviruses, and sequiviruses. The predicted amino acid sequence of the 3' proximal ORF2 (nucleotides 4390-7803) showed similarity to structural proteins in picorna-like viruses, especially the acute bee paralysis virus. Electron microscopic examination of negatively stained samples from virus-infected fire ants revealed isometric particles with a diameter of 31 nm, consistent with Picornaviridae. A survey for the fire ant virus from areas around Florida revealed a pattern of fairly widespread distribution. Among 168 nests surveyed, 22.9% were infected. The virus was found to infect all fire ant caste members and developmental stages, including eggs, early (1st-2nd) and late (3rd-4th) instars, worker pupae, workers, sexual pupae, alates ( male and female ), and queens. The virus, tentatively named S. invicta virus (SINV-1), appears to belong to the picorna-like viruses. We did not observe any perceptible symptoms among infected nests in the field. However, in every case where an SINV-1-infected colony was excavated from the field with an inseminated queen and held in the laboratory, all of the brood in these colonies died within 3 months

  14. Genome sequencing and analysis of the whitefly (Bemisia tabaci) MEAM1, one of the most important vectors for plant viruses

    Science.gov (United States)

    Among whiteflies, the Bemisia tabaci (Hemiptera: Aleyrodidae) species complex is particularly important because of its ability to transmit hundreds of plant viruses, resulting in the loss of billions of U.S. dollars on agronomically important crops such as tomato, cucurbits, cassava, and cotton worl...

  15. Retrospective seroepidemiological study of chikungunya infection in South Asia, Southeast Asia and the Pacific region.

    Science.gov (United States)

    Ngwe Tun, M M; Inoue, S; Thant, K Z; Talemaitoga, N; Aryati, A; Dimaano, E M; Matias, R R; Buerano, C C; Natividad, F F; Abeyewickreme, W; Thuy, N T T; Mai, L T Q; Hasebe, F; Hayasaka, D; Morita, K

    2016-08-01

    Chikungunya virus (CHIKV) and Ross River virus (RRV) of the genus Alphavirus, family Togaviridae are mainly transmitted by Aedes mosquitoes and the symptoms they cause in patients are similar to dengue. A chikungunya (CHIK) outbreak re-emerged in several Asian countries during 2005-2006. This study aimed to clarify the prevalence of CHIKV infection in suspected dengue patients in six countries in South Asia and Southeast Asia. Seven hundred forty-eight serum samples were from dengue-suspected patients in South Asia and Southeast Asia, and 52 were from patients in Fiji. The samples were analysed by CHIKV IgM capture ELISA, CHIKV IgG indirect ELISA and focus reduction neutralization test against CHIKV or RRV. CHIK-confirmed cases in South Asia, particularly Myanmar and Sri Lanka, were 4·6%, and 6·1%, respectively; and in Southeast Asia, particularly Indonesia, the Philippines and Vietnam, were 27·4%, 26·8% and 25·0%, respectively. It suggests that CHIK was widely spread in these five countries in Asia. In Fiji, no CHIK cases were confirmed; however, RRV-confirmed cases represented 53·6% of suspected dengue cases. It suggests that RRV is being maintained or occasionally entering from neighbouring countries and should be considered when determining a causative agent for dengue-like illness in Fiji. PMID:27018566

  16. Novel chikungunya vaccine candidate with an IRES-based attenuation and host range alteration mechanism.

    Directory of Open Access Journals (Sweden)

    Kenneth Plante

    2011-07-01

    Full Text Available Chikungunya virus (CHIKV is a reemerging mosquito-borne pathogen that has recently caused devastating urban epidemics of severe and sometimes chronic arthralgia. As with most other mosquito-borne viral diseases, control relies on reducing mosquito populations and their contact with people, which has been ineffective in most locations. Therefore, vaccines remain the best strategy to prevent most vector-borne diseases. Ideally, vaccines for diseases of resource-limited countries should combine low cost and single dose efficacy, yet induce rapid and long-lived immunity with negligible risk of serious adverse reactions. To develop such a vaccine to protect against chikungunya fever, we employed a rational attenuation mechanism that also prevents the infection of mosquito vectors. The internal ribosome entry site (IRES from encephalomyocarditis virus replaced the subgenomic promoter in a cDNA CHIKV clone, thus altering the levels and host-specific mechanism of structural protein gene expression. Testing in both normal outbred and interferon response-defective mice indicated that the new vaccine candidate is highly attenuated, immunogenic and efficacious after a single dose. Furthermore, it is incapable of replicating in mosquito cells or infecting mosquitoes in vivo. This IRES-based attenuation platform technology may be useful for the predictable attenuation of any alphavirus.

  17. The soft palate is an important site of adaptation for transmissible influenza viruses.

    Science.gov (United States)

    Lakdawala, Seema S; Jayaraman, Akila; Halpin, Rebecca A; Lamirande, Elaine W; Shih, Angela R; Stockwell, Timothy B; Lin, Xudong; Simenauer, Ari; Hanson, Christopher T; Vogel, Leatrice; Paskel, Myeisha; Minai, Mahnaz; Moore, Ian; Orandle, Marlene; Das, Suman R; Wentworth, David E; Sasisekharan, Ram; Subbarao, Kanta

    2015-10-01

    Influenza A viruses pose a major public health threat by causing seasonal epidemics and sporadic pandemics. Their epidemiological success relies on airborne transmission from person to person; however, the viral properties governing airborne transmission of influenza A viruses are complex. Influenza A virus infection is mediated via binding of the viral haemagglutinin (HA) to terminally attached α2,3 or α2,6 sialic acids on cell surface glycoproteins. Human influenza A viruses preferentially bind α2,6-linked sialic acids whereas avian influenza A viruses bind α2,3-linked sialic acids on complex glycans on airway epithelial cells. Historically, influenza A viruses with preferential association with α2,3-linked sialic acids have not been transmitted efficiently by the airborne route in ferrets. Here we observe efficient airborne transmission of a 2009 pandemic H1N1 (H1N1pdm) virus (A/California/07/2009) engineered to preferentially bind α2,3-linked sialic acids. Airborne transmission was associated with rapid selection of virus with a change at a single HA site that conferred binding to long-chain α2,6-linked sialic acids, without loss of α2,3-linked sialic acid binding. The transmissible virus emerged in experimentally infected ferrets within 24 hours after infection and was remarkably enriched in the soft palate, where long-chain α2,6-linked sialic acids predominate on the nasopharyngeal surface. Notably, presence of long-chain α2,6-linked sialic acids is conserved in ferret, pig and human soft palate. Using a loss-of-function approach with this one virus, we demonstrate that the ferret soft palate, a tissue not normally sampled in animal models of influenza, rapidly selects for transmissible influenza A viruses with human receptor (α2,6-linked sialic acids) preference.

  18. Solenopsis invicta virus 3: pathogenesis and stage specificity in red imported fire ants

    Science.gov (United States)

    Small Solenopsis invicta colonies were exposed to purified preparations of Solenopsis invicta virus 3 (SINV-3) to investigate virus pathogenesis at the colony level. Time course experiments revealed an infection exhibiting specificity for the adult stage (workers). SINV-3 genome and a capsid protein...

  19. Isolation and characterization of Solenopsis invicta virus 3, a new positive-strand RNA virus infecting the red imported fire ant, Solenopsis invicta

    International Nuclear Information System (INIS)

    We report the discovery of a new virus from the red imported fire ant, Solenopsis invicta. Solenopsis invicta virus 3 (SINV-3) represents the third virus discovered from this ant species using the metagenomics approach. The single (positive)-strand RNA, monopartite, bicistronic genome of SINV-3 was sequenced in entirety (GenBank accession number (FJ528584)), comprised of 10,386 nucleotides, and polyadenylated at the 3' terminus. This genome size was confirmed by Northern analysis. The genome revealed 2 large open reading frames (ORFs) in the sense orientation with an untranslated region (UTR) at each end and between the two ORFs. The 5' proximal ORF (ORF 1) encoded a predicted protein of 299.1 kDa (2580 amino acids). The 3' proximal ORF (ORF 2) encoded a predicted protein of 73.2 kDa (651 amino acids). RNA-dependent RNA polymerase (RdRp), helicase, and protease domains were recognized in ORF 1. SDS-PAGE separation of purified SINV-3 particles yielded 2 bands (ostensibly capsid proteins) with a combined molecular mass of 77.3 kDa which was similar to the mass predicted by ORF 2 (73.2 kDa). Phylogenetic analysis of the conserved amino acid sequences containing domains I to VIII of the RdRp from dicistroviruses, iflaviruses, plant small RNA viruses, picornaviruses, and 4 unassigned positive-strand RNA viruses revealed a trichotomous phenogram with SINV-3 and Kelp fly virus comprising a unique cluster. Electron microscopic examination of negatively stained samples of SINV-3 revealed isometric particles with apparent projections and a diameter of 27.3 ± 1.3 nm. SINV-3 was successfully transmitted to uninfected workers by feeding. The minus (replicative) strand of SINV-3 was detected in worker ants indicating replication of the virus. The possibility of using SINV-3 as a microbial control agent for fire ants is discussed.

  20. Epidemic situation of chikungunya fever in China%我国基孔肯雅热的流行状况

    Institute of Scientific and Technical Information of China (English)

    张彦; 刘起勇

    2011-01-01

    2010年10月,广东省东莞市暴发了我国首起基孔肯雅热社区聚集性疫情,打破了其长期以来以散在输入性病例为特征的流行现状.基孔肯雅热是一种由基孔肯雅病毒引起的急性传染病,伊蚊是其主要传播媒介.而我国大多数地区拥有其主要传播媒介埃及伊蚊和白纹伊蚊,一旦病原体侵入,可能暴发基孔肯雅热疫情.如何控制该疫情,防止疫情的进一步扩散,是摆在我们面前的当务之急.现就基孔肯雅病毒的病原学特征以及基孔肯雅热在我国历年的流行状况做一概述,以便更好地认识基孔肯雅热,为有效地监测和防治提供科学依据.%In October 2010, China's first community-based chikungunya fever (CHIK) outbreak occurred in Dongguan,Guangdong, a deviation from the long-term predominance of sporadic imported cases. CHIK is an acute infectious disease caused by chikungunya virus (CHIKV) and mainly transmitted by Aedes aegypti and Ae. albopictus, which are widely distributed in China.A CHIK outbreak may occur following the invasion of CHIKV. Hence, it is urgent to formulate control measures to prevent further spread of this disease. This study gives an overview of the pathogenic and epidemiological characteristics of CHIK to promote understanding of this disease and improve surveillance, prevention and control programs.

  1. The knowledge of the importance on the influenza virus a (H1N1: experience report

    Directory of Open Access Journals (Sweden)

    Jaine Kareny da Silva

    2016-01-01

    Full Text Available Background and Objectives: Although infection rates by influenza A H1N1, present reduction since 2010 through immunization, it is still notorious some cases and outbreaks of the disease in the country. To minimize such cases it is important, among other measures, the qualification of the health worker. In this sense, the objective was to describe the level of awareness of nursing professionals in a hospital Bahia interior, on the transmission of the H1N1 virus, symptoms and what PPE is needed in assisting patients with suspected or diagnostic confirmation. Methods: This is an experience report experienced by nursing students at the State University of Bahia, who developed curricular component activities Caring Process: Rationale and practice in a public hospital in Bahia. The report data is from the collection conducted with the nurses, addressing aspects of symptoms, transmission and personal protective equipment. Each professional nursing spontaneously answered the questions and the end was discussed each item aiming answer questions by promoting thus an educational activity based on the knowledge of professionals. Results: Although most participants recognize the personal protective equipment and the symptoms of the viral disease, some are still unaware of the transmission routes. Most received no training on the subject. Conclusion: It is necessary to implement a Center for Continuing Education to answer questions about this and other topics, but are not limited to specific actions and seeking partnerships with higher education institutions. KEYWORDS: Education, Continuing. Education, Nursing. Disease Transmission, Infectious. Communicable Disease Control

  2. Imported Zika Virus Infection from the Cook Islands into Australia, 2014

    OpenAIRE

    Pyke, Alyssa T; Daly, Michelle T.; Cameron, Jane N.; Moore, Peter R.; Taylor, Carmel T.; Glen R. Hewitson; Humphreys, Jan L.; Gair, Richard

    2014-01-01

    A female resident of Townsville, Queensland, Australia has been diagnosed with Zika virus infection following a recent trip to the Cook Islands. An initial serum sample collected in March, 2014 was positive by two separate Zika virus TaqMan real-time RT-PCRs and a pan-Flavivirus RT-PCR. Nucleotide sequencing and phylogenetics of the complete Cook Islands Zika virus envelope gene revealed 99.1% homology with a previous Cambodia 2010 sequence within the Asian lineage. In addition, IgG and IgM a...

  3. Basics of tumor development and importance of human papilloma virus (HPV for head and neck cancer [

    Directory of Open Access Journals (Sweden)

    Klussmann, Jens Peter

    2012-12-01

    Full Text Available [english] Head and Neck Squamous Cell Carcinomas (HNSCC are the 6 most common cancers worldwide. While incidence rates for cancer of the hypopharynx and larynx are decreasing, a significant increase in cancer of the oropharynx (OSCC is observed. Classical risk factors for HNSCC are smoking and alcohol. It has been shown for 25 to 60% of OSCC to be associated with an infection by oncogenic human papilloma viruses (HPV. The development of “common” cancer of the head and neck is substantially enhanced by an accumulation of genetic changes, which lead to an inactivation of tumor suppressor genes or activation of proto-oncogenes. A more or less uniform sequence of different DNA-damages leads to genetic instability. In this context, an early and frequent event is deletion on the short arm of chromosome 9, which results in inactivation of the p16-gene. In contrast, for HPV-induced carcinogenesis, expression of the viral proteins E6 and E7 is most important, since they lead to inactivation of the cellular tumor-suppressor-proteins p53 and Rb. The natural route of transoral infection is a matter of debate; peroral HPV-infections might be frequent and disappear uneventfully in most cases. Smoking seems to increase the probability for developing an HPV-associated OSCC. The association of HNSCC with HPV can be proven with established methods in clinical diagnostics. In addition to classical prognostic factors, diagnosis of HPV-association may become important for selection of future therapies. Prognostic relevance of HPV probably surmounts many known risk-factors, for example regional metastasis. Until now, no other molecular markers are established in clinical routine. Future therapy concepts may vary for the two subgroups of patients, particularly patients with HPV-associated OSCC may take advantage of less aggressive treatments. Finally, an outlook will be given on possible targeted therapies.

  4. Drosophila RNAi screen identifies host genes important for influenza virus replication

    OpenAIRE

    Hao, Linhui; Sakurai, Akira; Watanabe, Tokiko; Sorensen, Ericka; Nidom, Chairul A.; Newton, Michael A.; Ahlquist, Paul; Kawaoka, Yoshihiro

    2008-01-01

    All viruses rely on host cell proteins and their associated mechanisms to complete the viral life cycle. Identifying the host molecules that participate in each step of virus replication could provide valuable new targets for antiviral therapy, but this goal may take several decades to achieve with conventional forward genetic screening methods and mammalian cell cultures. Here we describe a novel genome-wide RNA interference (RNAi) screen in Drosophila1 that can be used to identify host gene...

  5. Importance of anticomplement immunofluorescence antibody titration for diagnosing varicella-zoster virus infection in Bell's palsy.

    OpenAIRE

    Shigeta, S; Baba, M.; Ogata, M; Nozaki, H.; Okuaki, A; Nakamura, S.

    1986-01-01

    Anticomplement Immunofluorescence was used for antibody titration against varicella-zoster virus (VZV) in 43 patients with peripheral facial palsy. Nine of 31 patients (29%) with Bell's palsy and eight of 12 patients (75%) with Ramsey-Hunt syndrome had anticomplement immunofluorescence antibody titres of greater than or equal to 1/10. On the other hand, none of 14 patients with herpes simplex virus (HSV) infection and 51 healthy adults showed anticomplement immunofluorescence antibody titres ...

  6. Human Leukocyte Antigen (HLA) Class I Restricted Epitope Discovery in Yellow Fewer and Dengue Viruses: Importance of HLA Binding Strength

    DEFF Research Database (Denmark)

    Lund, Ole; Nascimento, Eduardo J. M.; Maciel, Milton, Jr;

    2011-01-01

    Epitopes from all available full-length sequences of yellow fever virus (YFV) and dengue fever virus (DENV) restricted by Human Leukocyte Antigen class I (HLA-I) alleles covering 12 HLA-I supertypes were predicted using the NetCTL algorithm. A subset of 179 predicted YFV and 158 predicted DENV...... inoculated twice with the 17DD YFV vaccine strain. Three of the YFV A*02:01 restricted peptides activated T-cells from the infected mice in vitro. All three peptides that elicited responses had an HLA binding affinity of 2 nM or less. The results indicate the importance of the strength of HLA binding...

  7. Aedes (Stegomyia albopictus (Skuse: a potential vector of Zika virus in Singapore.

    Directory of Open Access Journals (Sweden)

    Pei-Sze Jeslyn Wong

    Full Text Available Zika virus (ZIKV is a little known arbovirus until it caused a major outbreak in the Pacific Island of Yap in 2007. Although the virus has a wide geographic distribution, most of the known vectors are sylvatic Aedes mosquitoes from Africa where the virus was first isolated. Presently, Ae. aegypti is the only known vector to transmit the virus outside the African continent, though Ae. albopictus has long been a suspected vector. Currently, Ae. albopictus has been shown capable of transmitting more than 20 arboviruses and its notoriety as an important vector came to light during the recent chikungunya pandemic. The vulnerability of Singapore to emerging infectious arboviruses has stimulated our interest to determine the competence of local Ae. albopictus to transmit ZIKV.To determine the competence of Ae. albopictus to ZIKV, we orally infected local mosquito strains to a Ugandan strain virus. Fully engorged mosquitoes were maintained in an environmental chamber set at 29°C and 80-85%RH. Twelve mosquitoes were then sampled daily from day one to seven and on day 10 and 14 post infection (pi. Zika virus titre in the midgut and salivary glands of each mosquito were determined using tissue culture infectious dose50 assay, while transmissibility of the virus was determined by detecting viral antigen in the mosquito saliva by qRT-PCR. High dissemination and transmission rate of ZIKV were observed. By day 7-pi, all mosquitoes have disseminated infection and 73% of these mosquitoes have ZIKV in their saliva. By day 10-pi, all mosquitoes were potentially infectious.The study highlighted the potential of Ae. albopictus to transmit ZIKV and the possibility that the virus could be established locally. Nonetheless, the threat of ZIKV can be mitigated by existing dengue and chikungunya control program being implemented in Singapore.

  8. Gambaran Perilaku Mahasiswa Fakultas Kedokteran Universitas Sumatera Utara terhadap Demam Chikungunya Tahun 2010

    OpenAIRE

    Nik Arif Ridhwan Bin Azemi

    2011-01-01

    Chikungunya Fever is one of spreading disease which is its cases tend to increase day by day. Chikungunya is similar to Dengue Hemorrhagic Fever, both transmitted by Aedes aegypti mosquitoes. In North Sumatera, first Chikungunya cases appeared on 2005 and till now its already spread to few districts. The aim of this research is to know the knowledge, attitude and practice among the student of the Medical Faculty in the University of North Sumatera about Chikungunya Fever. This research u...

  9. 基孔肯雅病毒,不容小觑肆虐美洲的“登革病毒”%Watch out for Chikungunya

    Institute of Scientific and Technical Information of China (English)

    盛子洋; 高娜; 安静

    2015-01-01

    2014年,一种类似于登革热的传染病———基孔肯雅热席卷了中南美洲,其病原体为基孔肯雅病毒,隶属于披膜病毒科甲病毒属的单股正链RN A病毒,传播媒介主要是伊蚊属,尤其是白纹伊蚊和埃及伊蚊。基孔肯雅热的临床症状与登革热十分相似,临床上需要鉴别诊断。2010年该疾病在我国广东曾小规模流行,其对人民健康造成的危害以及所带来的经济负担不亚于登革热,应高度重视,遏制其蔓延。%Numerous Chikungunya outbreaks have occurred throughout Central and South America in 201 4.Around a million of local residents suffered.Chikungunya virus is a member of Genus Alphavirus,Family Togaviridae.The genome is a positive-sense single-stranded RNA.Genus Aedes mosquitoes are main vectors,especially Aedes albopictus and Aedes aegypti.The disease caused by the virus shows some similarities with Dengue fever in clinical manifestations.We need to pay attention to diagnosis of those two diseases.A small-scale epidemic of Chikungunya occurred struck in Guangdong Province in 201 0 with the degree of health threat.It's in great need of controlling the spread of Chikungunya virus,for its economic burden is no less than that of Dengue virus.

  10. Pathogenesis of Congenital Rubella Virus Infection in Human Fetuses: Viral Infection in the Ciliary Body Could Play an Important Role in Cataractogenesis

    Directory of Open Access Journals (Sweden)

    Thong Van Nguyen

    2015-01-01

    Interpretation: Our study based on the pathological examination demonstrated that the rubella virus infection occurred via systemic organs of human fetuses. This fact was confirmed by immunohistochemistry and direct detection of viral RNA in multiple organs. To the best of our knowledge, this study is the first report demonstrating that the rubella virus infection occurred via systemic organs of the human body. Importantly, virus infection of the ciliary body could play an important role in cataractogenesis.

  11. A new positive-strand RNA virus with unique genome characteristics from the red imported fire ant, Solenopsis invicta.

    Science.gov (United States)

    Valles, Steven M; Strong, Charles A; Hashimoto, Yoshifumi

    2007-09-01

    We report the discovery of a new virus with unique genome characteristics from the red imported fire ant, Solenopsis invicta. This virus represents the second identified from this ant species. It is provisionally named Solenopsis invicta virus 2 (SINV-2). The SINV-2 genome was constructed by compiling sequences from successive 5' RACE reactions, a 3' RACE reaction, and expressed sequence tag, c246 (accession number EH413675), from a fire ant expression library. The SINV-2 genome structure was monopartite, polycistronic and RNA-based. The genome consensus sequence (EF428566) was 11,303 nucleotides in length, excluding the poly(A) tail present on the 3' end. Analysis of the genome revealed 4 major open reading frames (ORFs; comprised of > or =100 codons) and 5 minor ORFs (comprised of 50-99 codons) in the sense orientation. No large ORFs were found in the inverse orientation suggesting that the SINV-2 genome was from a positive-strand RNA virus. Further evidence for this conclusion includes abolished RT-PCR amplification by RNase treatment of SINV-2 nucleic acid template, and failure to amplify without first conducting cDNA synthesis. Blastp analysis indicated that ORF 4 contained conserved domains of an RNA-dependent RNA polymerase, helicase, and protease, characteristic of positive-strand RNA viruses. However, the protease domain and putative structural proteins (ORFs 1, 2, and 3) were less well conserved. Phylogenetic analysis of the RdRp, helicase, and ORF 1 indicate unique placement of SINV-2 exclusive from the Dicistroviridae, iflaviruses, Picornaviridae, and plant small RNA viruses. PMID:17477949

  12. Mapping global environmental suitability for Zika virus.

    OpenAIRE

    Messina, JP; Kraemer, MU; Brady, OJ; Pigott, DM; Shearer, FM; Weiss, DJ; Golding, N.; Ruktanonchai, CW; Gething, PW; Cohn, E.; Brownstein, JS; Khan, K; Tatem, AJ; Jaenisch, T; Murray, CJ

    2016-01-01

    Zika virus was discovered in Uganda in 1947 and is transmitted by Aedes mosquitoes, which also act as vectors for dengue and chikungunya viruses throughout much of the tropical world. In 2007, an outbreak in the Federated States of Micronesia sparked public health concern. In 2013, the virus began to spread across other parts of Oceania and in 2015, a large outbreak in Latin America began in Brazil. Possible associations with microcephaly and Guillain-Barré syndrome observed in this outbreak ...

  13. Nuclear export and import of human hepatitis B virus capsid protein and particles.

    Directory of Open Access Journals (Sweden)

    Hung-Cheng Li

    Full Text Available It remains unclear what determines the subcellular localization of hepatitis B virus (HBV core protein (HBc and particles. To address this fundamental issue, we have identified four distinct HBc localization signals in the arginine rich domain (ARD of HBc, using immunofluorescence confocal microscopy and fractionation/Western blot analysis. ARD consists of four tight clustering arginine-rich subdomains. ARD-I and ARD-III are associated with two co-dependent nuclear localization signals (NLS, while ARD-II and ARD-IV behave like two independent nuclear export signals (NES. This conclusion is based on five independent lines of experimental evidence: i Using an HBV replication system in hepatoma cells, we demonstrated in a double-blind manner that only the HBc of mutant ARD-II+IV, among a total of 15 ARD mutants, can predominantly localize to the nucleus. ii These results were confirmed using a chimera reporter system by placing mutant or wild type HBc trafficking signals in the heterologous context of SV40 large T antigen (LT. iii By a heterokaryon or homokaryon analysis, the fusion protein of SV40 LT-HBc ARD appeared to transport from nuclei of transfected donor cells to nuclei of recipient cells, suggesting the existence of an NES in HBc ARD. This putative NES is leptomycin B resistant. iv We demonstrated by co-immunoprecipitation that HBc ARD can physically interact with a cellular factor TAP/NXF1 (Tip-associated protein/nuclear export factor-1, which is known to be important for nuclear export of mRNA and proteins. Treatment with a TAP-specific siRNA strikingly shifted cytoplasmic HBc to nucleus, and led to a near 7-fold reduction of viral replication, and a near 10-fold reduction in HBsAg secretion. v HBc of mutant ARD-II+IV was accumulated predominantly in the nucleus in a mouse model by hydrodynamic delivery. In addition to the revised map of NLS, our results suggest that HBc could shuttle rapidly between nucleus and cytoplasm via a novel

  14. Functional importance of dengue virus maturation : infectious properties of immature virions

    NARCIS (Netherlands)

    Zybert, Izabela A.; van der Ende-Metselaar, Heidi; Wilschut, Jan; Smit, Jolanda M.

    2008-01-01

    Prior to the release of flavivirus particles from infected cells, the viral surface protein prM is cleaved to M by the cellular enzyme furin. For dengue virus (DENV), this maturation process appears to be very inefficient since a high proportion of progeny virions contain uncleaved prM. Furthermore,

  15. Working with Zika and Usutu Viruses In Vitro

    Science.gov (United States)

    Barr, Kelli L.; Anderson, Benjamin D.; Prakoso, Dhani; Long, Maureen T.

    2016-01-01

    Usutu (USUV) and Zika (ZIKV) viruses are emerging arboviruses of significant medical and veterinary importance. These viruses have not been studied as well as other medically important arboviruses such as West Nile (WNV), dengue (DENV), or chikungunya (CHIKV) viruses. As such, information regarding the behavior of ZIKV and USUV viruses in the laboratory is dated. Usutu virus re-emerged in Austria in 2001 and has since spread throughout the European and Asian continents causing significant mortality among birds. Zika virus has recently appeared in the Western Hemisphere and has exhibited high rates of birth defects and sexual transmission. Information about the characteristics of USUV and ZIKV viruses are needed to better understand the transmission, dispersal, and adaptation of these viruses in new environments. Since their initial characterization in the middle of last century, technologies and reagents have been developed that could enhance our abilities to study these pathogens. Currently, standard laboratory methods for these viruses are limited to 2–3 cell lines and many assays take several days to generate meaningful data. The goal of this study was to characterize these viruses in cells from multiple diverse species. Cell lines from 17 species were permissive to both ZIKV and USUV. These viruses were able to replicate to significant titers in most of the cell lines tested. Moreover, cytopathic effects were observed in 8 of the cell lines tested. These data indicate that a variety of cell lines can be used to study ZIKV and USUV infection and may provide an updated foundation for the study of host-pathogen interactions, model development, and the development of therapeutics. PMID:27541001

  16. Working with Zika and Usutu Viruses In Vitro.

    Science.gov (United States)

    Barr, Kelli L; Anderson, Benjamin D; Prakoso, Dhani; Long, Maureen T

    2016-08-01

    Usutu (USUV) and Zika (ZIKV) viruses are emerging arboviruses of significant medical and veterinary importance. These viruses have not been studied as well as other medically important arboviruses such as West Nile (WNV), dengue (DENV), or chikungunya (CHIKV) viruses. As such, information regarding the behavior of ZIKV and USUV viruses in the laboratory is dated. Usutu virus re-emerged in Austria in 2001 and has since spread throughout the European and Asian continents causing significant mortality among birds. Zika virus has recently appeared in the Western Hemisphere and has exhibited high rates of birth defects and sexual transmission. Information about the characteristics of USUV and ZIKV viruses are needed to better understand the transmission, dispersal, and adaptation of these viruses in new environments. Since their initial characterization in the middle of last century, technologies and reagents have been developed that could enhance our abilities to study these pathogens. Currently, standard laboratory methods for these viruses are limited to 2-3 cell lines and many assays take several days to generate meaningful data. The goal of this study was to characterize these viruses in cells from multiple diverse species. Cell lines from 17 species were permissive to both ZIKV and USUV. These viruses were able to replicate to significant titers in most of the cell lines tested. Moreover, cytopathic effects were observed in 8 of the cell lines tested. These data indicate that a variety of cell lines can be used to study ZIKV and USUV infection and may provide an updated foundation for the study of host-pathogen interactions, model development, and the development of therapeutics. PMID:27541001

  17. Emerging mosquito-borne viruses: transmission and modulation of host defence

    NARCIS (Netherlands)

    Fros, J.J.

    2015-01-01

    Summary Two highly pathogenic arthropod-borne (arbo)viruses, West Nile virus (WNV) and chikungunya virus (CHIKV), recently (re-)emerged in both Europe and the Americas. This resulted in large-scale epidemics of severe encephalitic and arthritogenic human disease, respectively. Both

  18. Importance of hepatitis C virus-associated insulin resistance:Therapeutic strategies for insulin sensitization

    Institute of Scientific and Technical Information of China (English)

    Takumi; Kawaguchi; Michio; Sata

    2010-01-01

    Insulin resistance is one of the pathological features in patients with hepatitis C virus(HCV) infection.Generally,persistence of insulin resistance leads to an increase in the risk of life-threatening complications such as cardiovascular diseases.However,these complications are not major causes of death in patients with HCV-associated insulin resistance.Indeed,insulin resistance plays a crucial role in the development of various complications and events associated with HCV infection.Mounting evidence indic...

  19. Gene synthesis,cloning,prokaryotic expression and analysis of chikungunya virus E2 glycoprotein%基孔肯雅病毒包膜蛋白E2的全基因合成及原核表达

    Institute of Scientific and Technical Information of China (English)

    章萍萍; 邓松华; 潘卫; 曹洁; 陈秋莉; 王锦红; 张华群; 葛宜兵; 祁培培; 刘超

    2012-01-01

    -E2( 1 - 404 aa ) protein was synthesized by OE-PCR and two prokaryotic expression plasmids,and pET21b-E2( 1 -404 aa ) and pET21b-E2( 1 -350 aa ) were constructed successfully. The plasmids were induced by IPTG and SDS-PAGE, which showed that the production of the deletion mutant E2( 1 -350 aa ) was much higher than that of pET21b-E2( 1 -404 ). Conclusion The hydrophobic transmembrane domain ( 351 -378 aa ) of E2 protein plays an important role in E2 production in E. Coli and production of the mutant with the domain deleted is significantly higher than that of full-length E2 protein.

  20. Probability of introduction of exotic strains of bluetongue virus into the US and into California through importation of infected cattle.

    Science.gov (United States)

    Hoar, Bruce R; Carpenter, Tim E; Singer, Randall S; Gardner, Ian A

    2004-12-15

    Strategies designed to minimize the probability of bluetongue virus (BTV) introduction to new areas should be based on a quantitative assessment of the probability of actually establishing the virus once it is introduced. The risk of introducing a new strain of bluetongue virus into a region depends on the number of viremic animals that enter and the competency of local vectors to transmit the virus. We used Monte Carlo simulation to model the probability of introducing BTV into California, USA, and the US through importation of cattle. Records of cattle and calf imports into California and the US were obtained, as was seroprevalence information from the exporting countries. A simulation model was constructed to evaluate the probability of importing either a viremic PCR-negative animal after 14-day quarantine, a c-ELISA BTV-antibody-negative animal after 28-day quarantine, or an untested viremic animal after 100-day quarantine into California and into the US. We found that for animals imported to the US, the simulated (best to worst scenarios) median percentage that tested positive for BTV-antibody ranged from 5.4 to 7.2%, while for the subset imported to California, the simulated median percentage that tested positive for BTV-antibody ranged from 20.9 to 78.9%. Using PCR, for animals imported to the US these values were 71.8-85.3%, and for those imported to California, the simulated median that test positive ranged from 74.3 to 92.4%. The probability that an imported animal was BTV-viremic is very low regardless of the scenario selected (median probability=0.0%). The probability of introducing an exotic strain of BTV into California or the US by importing infected cattle was remote, and the current Office International des Epizooties (OIE) recommendation of either a final PCR test performed 14 days after entry into quarantine, a c-ELISA performed 28 days after entry into quarantine or a 100-day quarantine with no testing requirement was adequate to protect cattle

  1. Expressed sequence tags from the red imported fire ant, Solenopsis invicta: annotation and utilization for discovery of viruses.

    Science.gov (United States)

    Valles, Steven M; Strong, Charles A; Hunter, Wayne B; Dang, Phat M; Pereira, Roberto M; Oi, David H; Williams, David F

    2008-09-01

    An expression library was created and 2304 clones sequenced from a monogyne colony of Solenopsis invicta. The primary intention of the project was to utilize homologous gene identification to facilitate discovery of viruses infecting this ant pest that could potentially be used in pest management. Additional genes were identified from the ant host and associated pathogens that serve as an important resource for studying these organisms. After assembly and removal of mitochondrial and poor quality sequences, 1054 unique sequences were yielded and deposited into the GenBank database under Accession Nos. EH412746 through EH413799. At least nine expressed sequence tags (ESTs) were identified as possessing microsatellite motifs and 15 ESTs exhibited significant homology with microsporidian genes. These sequences most likely originated from Thelohania solenopsae, a well-characterized microsporidian that infects S. invicta. Six ESTs exhibited significant homology with single-stranded RNA viruses (3B4, 3F6, 11F1, 12G12, 14D5, and 24C10). Subsequent analysis of these putative viral ESTs revealed that 3B4 was most likely a ribosomal gene of S. invicta, 11F1 was a single-stranded RNA (ssRNA) virus contaminant introduced into the colony from the cricket food source, 12G12 appeared to be a plant-infecting tenuivirus also introduced into the colony as a field contaminant, and 3F6, 14D5, and 24C10 were all from a unique ssRNA virus found to infect S. invicta. The sequencing project illustrates the utility of this method for discovery of viruses and pathogens that may otherwise go undiscovered. PMID:18329665

  2. A chikungunya outbreak associated with the vector Aedes albopictus in remote villages of Gabon.

    Science.gov (United States)

    Paupy, Christophe; Kassa Kassa, Fabrice; Caron, Mélanie; Nkoghé, Dieudonné; Leroy, Eric M

    2012-02-01

    Chikungunya virus (CHIKV) recently caused major urban outbreaks in central African countries such as the Democratic Republic of Congo (DRC), Cameroon, and Gabon. In Gabon, the tiger mosquito Aedes albopictus was shown to be the main CHIKV vector during the 2007 outbreak. This invasive Asian species was first identified in Gabon in early 2007, and was thought to be restricted mainly to coastal provinces where urban epidemic CHIKV foci were recorded. Here we report a CHIKV outbreak in a small cluster of villages isolated in the deep forest of southern Gabon, in which A. albopictus was the main vector. This observation indicates concomitant geographic and ecological spread of CHIKV activity and A. albopictus in remote environments in central Africa, as well as an enhanced risk of propagation of epidemic arboviruses.

  3. Detection of spring viraemia of carp virus in imported amphibians reveals an unanticipated foreign animal disease threat.

    Science.gov (United States)

    Ip, Hon S; Lorch, Jeffrey M; Blehert, David S

    2016-01-01

    Global translocation of plants and animals is a well-recognized mechanism for introduction of pathogens into new regions. To mitigate this risk, various tools such as preshipment health certificates, quarantines, screening for specific disease agents and outright bans have been implemented. However, such measures only target known infectious agents and their hosts and may fail to prevent translocation of even well-recognized pathogens if they are carried by novel host species. In a recent example, we screened an imported shipment of Chinese firebelly newts (Cynops orientalis) for Batrachochytrium salamandrivorans, an emergent fungal pathogen of salamanders. All animals tested negative for the fungus. However, a virus was cultured from internal organs from 7 of the 11 individual dead salamanders and from two pools of tissues from four additional dead animals. Sequencing of a portion of the glycoprotein gene from all viral isolates indicated 100% identity and that they were most closely related to spring viraemia of carp virus (SVCV). Subsequently, SVCV-specific PCR testing indicated the presence of virus in internal organs from each of the four animals previously pooled, and whole-genome sequencing of one of the viral isolates confirmed genomic arrangement characteristic of SVCV. SVCV is a rhabdovirus pathogen of cyprinid fish that is listed as notifiable to the Office International des Epizooties. This discovery reveals a novel route for potential spillover of this economically important pathogen as rhabdovirus has not previously been documented in amphibians. PMID:27599472

  4. Detection of spring viraemia of carp virus in imported amphibians reveals an unanticipated foreign animal disease threat.

    Science.gov (United States)

    Ip, Hon S; Lorch, Jeffrey M; Blehert, David S

    2016-09-07

    Global translocation of plants and animals is a well-recognized mechanism for introduction of pathogens into new regions. To mitigate this risk, various tools such as preshipment health certificates, quarantines, screening for specific disease agents and outright bans have been implemented. However, such measures only target known infectious agents and their hosts and may fail to prevent translocation of even well-recognized pathogens if they are carried by novel host species. In a recent example, we screened an imported shipment of Chinese firebelly newts (Cynops orientalis) for Batrachochytrium salamandrivorans, an emergent fungal pathogen of salamanders. All animals tested negative for the fungus. However, a virus was cultured from internal organs from 7 of the 11 individual dead salamanders and from two pools of tissues from four additional dead animals. Sequencing of a portion of the glycoprotein gene from all viral isolates indicated 100% identity and that they were most closely related to spring viraemia of carp virus (SVCV). Subsequently, SVCV-specific PCR testing indicated the presence of virus in internal organs from each of the four animals previously pooled, and whole-genome sequencing of one of the viral isolates confirmed genomic arrangement characteristic of SVCV. SVCV is a rhabdovirus pathogen of cyprinid fish that is listed as notifiable to the Office International des Epizooties. This discovery reveals a novel route for potential spillover of this economically important pathogen as rhabdovirus has not previously been documented in amphibians.

  5. Detection of spring viraemia of carp virus in imported amphibians reveals an unanticipated foreign animal disease threat

    Science.gov (United States)

    Ip, Hon S.; Lorch, Jeffrey M.; Blehert, David

    2016-01-01

    Global translocation of plants and animals is a well-recognized mechanism for introduction of pathogens into new regions. To mitigate this risk, various tools such as preshipment health certificates, quarantines, screening for specific disease agents and outright bans have been implemented. However, such measures only target known infectious agents and their hosts and may fail to prevent translocation of even well-recognized pathogens if they are carried by novel host species. In a recent example, we screened an imported shipment of Chinese firebelly newts (Cynops orientalis) for Batrachochytrium salamandrivorans, an emergent fungal pathogen of salamanders. All animals tested negative for the fungus. However, a virus was cultured from internal organs from 7 of the 11 individual dead salamanders and from two pools of tissues from four additional dead animals. Sequencing of a portion of the glycoprotein gene from all viral isolates indicated 100% identity and that they were most closely related to spring viraemia of carp virus (SVCV). Subsequently, SVCV-specific PCR testing indicated the presence of virus in internal organs from each of the four animals previously pooled, and whole-genome sequencing of one of the viral isolates confirmed genomic arrangement characteristic of SVCV. SVCV is a rhabdovirus pathogen of cyprinid fish that is listed as notifiable to the Office International des Epizooties. This discovery reveals a novel route for potential spillover of this economically important pathogen as rhabdovirus has not previously been documented in amphibians.

  6. Insilico modeling of Wolbachia and its potentials in combating mosquito borne diseases Chikungunya and Dengue

    Directory of Open Access Journals (Sweden)

    N.M.Guruprasad

    2013-09-01

    Full Text Available Mosquito borne diseases are major health burden both in tropical and subtropical regions. The enormous use of insecticides to control mosquitoes causes biomagnification of chemicals in environment and mosquitoes have developed resistance to insecticides. The inefficiency of insecticides to combat mosquitoes prompted researchers to develop efficient alternative methods. Wolbachia endosymbiont is a one of efficient new approach to control mosquitoes. Wolbachia strain invade mosquitoes biology by reducing host lifespan, phenotype and inhibit virus replication. In the present study, insilico modeling and docking of Wolbachia and human pathogens Chikungunya (CHIK and Dengue (DEN virus was done. Docking is the method to find the binding affinity of protein and ligand complex molecules for finding potential inhibitor. Using Hex, we obtained energy total (e-total values in kcal/mol for all docked complex. In the contest of overall analyzing the docking E-total values of docked complexes reveals that WSP-B has show strong binding affinity than WSP-A to both DEN and CHIK. Based on obtained result, we suggest WSP-B has potential inhibitor for both DEN and CHIK virus. Further, biophysical characterization of Wolbachia will help to develop a drug to combat CHIK and DEN viruses.

  7. Discovery of berberine, abamectin and ivermectin as antivirals against chikungunya and other alphaviruses.

    Science.gov (United States)

    Varghese, Finny S; Kaukinen, Pasi; Gläsker, Sabine; Bespalov, Maxim; Hanski, Leena; Wennerberg, Krister; Kümmerer, Beate M; Ahola, Tero

    2016-02-01

    Chikungunya virus (CHIKV) is an arthritogenic arbovirus of the Alphavirus genus, which has infected millions of people after its re-emergence in the last decade. In this study, a BHK cell line containing a stable CHIKV replicon with a luciferase reporter was used in a high-throughput platform to screen approximately 3000 compounds. Following initial validation, 25 compounds were chosen as primary hits for secondary validation with wild type and reporter CHIKV infection, which identified three promising compounds. Abamectin (EC50 = 1.5 μM) and ivermectin (EC50 = 0.6 μM) are fermentation products generated by a soil dwelling actinomycete, Streptomyces avermitilis, whereas berberine (EC50 = 1.8 μM) is a plant-derived isoquinoline alkaloid. They inhibited CHIKV replication in a dose-dependent manner and had broad antiviral activity against other alphaviruses--Semliki Forest virus and Sindbis virus. Abamectin and ivermectin were also active against yellow fever virus, a flavivirus. These compounds caused reduced synthesis of CHIKV genomic and antigenomic viral RNA as well as downregulation of viral protein expression. Time of addition experiments also suggested that they act on the replication phase of the viral infectious cycle.

  8. Outbreak of hepatitis C virus infections at an outpatient hemodialysis facility: the importance of infection control competencies.

    Science.gov (United States)

    Rao, Agam K; Luckman, Emily; Wise, Matthew E; MacCannell, Taranisia; Blythe, David; Lin, Yulin; Xia, Guoliang; Drobeniuc, Jan; Noble-Wang, Judith; Arduino, Matthew J; Thompson, Nicola D; Patel, Priti R; Wilson, Lucy E

    2013-01-01

    In the United States, the prevalence of hepatitis C virus infection among patients treated in hemodialysis facilities is five times higher than among the general population. This study investigated eight new hepatitis C virus infections among patients treated at an outpatient hemodialysis facility. Epidemiologic investigation and viral sequencing demonstrated that transmission likely occurred between patients typically treated during the same or consecutive shifts at the same or a nearby station. Several infection control breaches were observed including lapses involving the preparation, handling, and administration of parenteral medications. Improved infection control education and training for all hemodialysis facility staff is an important component of assuring adherence to appropriate procedures and preventing future outbreaks. PMID:23785746

  9. Mathematical modeling of Chikungunya fever control

    Science.gov (United States)

    Hincapié-Palacio, Doracelly; Ospina, Juan

    2015-05-01

    Chikungunya fever is a global concern due to the occurrence of large outbreaks, the presence of persistent arthropathy and its rapid expansion throughout various continents. Globalization and climate change have contributed to the expansion of the geographical areas where mosquitoes Aedes aegypti and Aedes albopictus (Stegomyia) remain. It is necessary to improve the techniques of vector control in the presence of large outbreaks in The American Region. We derive measures of disease control, using a mathematical model of mosquito-human interaction, by means of three scenarios: a) a single vector b) two vectors, c) two vectors and human and non-human reservoirs. The basic reproductive number and critical control measures were deduced by using computer algebra with Maple (Maplesoft Inc, Ontario Canada). Control measures were simulated with parameter values obtained from published data. According to the number of households in high risk areas, the goals of effective vector control to reduce the likelihood of mosquito-human transmission would be established. Besides the two vectors, if presence of other non-human reservoirs were reported, the monthly target of effective elimination of the vector would be approximately double compared to the presence of a single vector. The model shows the need to periodically evaluate the effectiveness of vector control measures.

  10. DENGUE, CHIKUNGUNYA E EBOLA: VIROSES AMBIENTAIS

    Directory of Open Access Journals (Sweden)

    Thereza Cristina Ferreira Camello

    2014-12-01

    Full Text Available DOI: 10.12957/sustinere.2014.14122Várias viroses emergentes ou reemergentes podem ser veiculadas por mosquitos. Aedes aegypti e Aedes albopictus, os mesmos que transmitem o vírus da dengue e da febre amarela, podem disseminar o vírus Chikungunya que este ano no Brasil já fez cerca de 1000 casos confirmados. A doença tem parâmetros semelhantes aos da Dengue, e embora a taxa de letalidade seja muito baixa, sequelas podem permanecer no individuo por um ano. Em 2014 a partir de setembro o mundo observou perplexo a ressurgência de um vírus hemorrágico letal, em uma das piores epidemias já ocorridas no continente africano. O vírus Ebola atingiu mais de 6000 pessoas. Estudos no sentido de melhorar as estratégias de contenção da disseminação de vetores e dos vírus devem ser estabelecidas, enquanto aguardamos a produção de vacinas eficazes. O mundo não é imune a uma infecção endêmica, localizada no interior de um continente e não estamos preparados para atender uma demanda deste porte.

  11. Dose response of red imported fire ant colonies to Solenopsis invicta virus 3.

    Science.gov (United States)

    Valles, Steven M; Porter, Sanford D

    2015-10-01

    Baiting tests were conducted to evaluate the effect of increasing Solenopsis invicta virus 3 (SINV-3) dose on fire ant colonies. Actively growing early-stage fire ant (Solenopsis invicta Buren) laboratory colonies were pulse-exposed for 24 hours to six concentrations of SINV-3 (10(1), 10(3), 10(5), 10(7), 10(9) genome equivalents/μl) in 1 ml of a 10 % sucrose bait and monitored regularly for two months. SINV-3 concentration had a significant effect on colony health. Brood rating (proportion of brood to worker ants) began to depart from the control group at 19 days for the 10(9) concentration and 26 days for the 10(7) concentration. At 60 days, brood rating was significantly lower among colonies treated with 10(9), 10(7), and 10(5) SINV-3 concentrations. The intermediate concentration, 10(5), appeared to cause a chronic, low-level infection with one colony (n = 9) supporting virus replication. Newly synthesized virus was not detected in any fire ant colonies treated at the 10(1) concentration, indicating that active infections failed to be established at this level of exposure. The highest bait concentration chosen, 10(9), appeared most effective from a control aspect; mean colony brood rating at this concentration (1.1 ± 0.9 at the 60 day time point) indicated poor colony health with minimal brood production. No clear relationship was observed between the quantity of plus genome strand detected and brood rating. Conversely, there was a strong relationship between the presence of the replicative genome strand and declining brood rating, which may serve as a predictor of disease severity. Recommendations for field treatment levels to control fire ants with SINV-3 are discussed. PMID:26162304

  12. Ubiquitin-regulated nuclear-cytoplasmic trafficking of the Nipah virus matrix protein is important for viral budding.

    Directory of Open Access Journals (Sweden)

    Yao E Wang

    Full Text Available Paramyxoviruses are known to replicate in the cytoplasm and bud from the plasma membrane. Matrix is the major structural protein in paramyxoviruses that mediates viral assembly and budding. Curiously, the matrix proteins of a few paramyxoviruses have been found in the nucleus, although the biological function associated with this nuclear localization remains obscure. We report here that the nuclear-cytoplasmic trafficking of the Nipah virus matrix (NiV-M protein and associated post-translational modification play a critical role in matrix-mediated virus budding. Nipah virus (NiV is a highly pathogenic emerging paramyxovirus that causes fatal encephalitis in humans, and is classified as a Biosafety Level 4 (BSL4 pathogen. During live NiV infection, NiV-M was first detected in the nucleus at early stages of infection before subsequent localization to the cytoplasm and the plasma membrane. Mutations in the putative bipartite nuclear localization signal (NLS and the leucine-rich nuclear export signal (NES found in NiV-M impaired its nuclear-cytoplasmic trafficking and also abolished NiV-M budding. A highly conserved lysine residue in the NLS served dual functions: its positive charge was important for mediating nuclear import, and it was also a potential site for monoubiquitination which regulates nuclear export of the protein. Concordantly, overexpression of ubiquitin enhanced NiV-M budding whereas depletion of free ubiquitin in the cell (via proteasome inhibitors resulted in nuclear retention of NiV-M and blocked viral budding. Live Nipah virus budding was exquisitely sensitive to proteasome inhibitors: bortezomib, an FDA-approved proteasome inhibitor for treating multiple myeloma, reduced viral titers with an IC(50 of 2.7 nM, which is 100-fold less than the peak plasma concentration that can be achieved in humans. This opens up the possibility of using an "off-the-shelf" therapeutic against acute NiV infection.

  13. Anti-chikungunya activity of luteolin and apigenin rich fraction from Cynodon dactylon

    Institute of Scientific and Technical Information of China (English)

    Krishnan Saravana Murali; Srinivasan Sivasubramanian; Savariar Vincent; Shanmugaraj Bala Murugan; Bupesh Giridaran; Sundaram Dinesh; Palani Gunasekaran; Kaveri Krishnasamy; Ramalingam Sathishkumar

    2015-01-01

    Objective:To obtain luteolin and apigenin rich fraction from the ethanolic extract ofCynodon dactylon (L.) (C. dactylon) Pers and evaluate the fraction’s cytotoxicity and anti-Chikungunya potential using Vero cells.Methods:The ethanolic extract ofC. dactylon was subjected to silica gel column chromatography to obtain anti-chikungunya virus (CHIKV) fraction. Reverse phase-HPLC and GC-MS studies were carried out to identify the major phytochemicals in the fraction using phytochemical standards. Cytotoxicity and the potential of the fraction against CHIKV were evaluatedin vitrousing Vero cells. Reduction in viral replication was assessed by reverse transcriptase-polymerase chain reaction (RT-PCR) after treating the viral infected Vero cells with the fraction.Results:Reverse Phase-HPLC and GC-MS studies confirmed the presence of flavonoids, luteolin and apigenin as major phytochemicals in the anti-CHIKV ethanolic fraction ofC. dactylon. The fraction was found to exhibit potent viral inhibitory activity (about 98%) at the concentration of 50 µg/mL as observed by reduction in cytopathic effect, and the cytotoxic concentration of the fraction was found to be 250 µg/mL. RT-PCR analyses indicated that the reduction in viral mRNA synthesis in fraction treated infected cells was much higher than the viral infected control cells.Conclusions:Luteolin and apigenin rich ethanolic fraction fromC. dactylon can be utilized as a potential therapeutic agent against CHIKV infection as the fraction does not show cytotoxicity while inhibiting the virus.

  14. The importance of alfalfa mosaic virus coat protein dimers in the initiation of replication.

    Science.gov (United States)

    Choi, Jiwon; Kim, Bong-Suk; Zhao, Xiaoxia; Loesch-Fries, Sue

    2003-01-01

    Deletion and substitution mutations affecting the oligomerization of alfalfa mosaic virus (AMV) coat protein (CP) were studied in protoplasts to determine their effect on genome activation, an early step in AMV replication. The CP mutants that formed dimers, CPDeltaC9 and CPC-A(R)F, were highly active in initiating replication with 63-84% of wild-type (wt) CP activity. However, all mutants that did not form dimers, CPDeltaC18, CPDeltaC19, CPC-WFP, and CPC-W, were much less active with 19-33% of wt CP activity. The accumulation and solubility of mutant CPs expressed from a virus-based vector in Nicotiana benthamiana were similar to that of wt CP. Analysis of CP-RNA interactions indicated that CP dimers and CP monomers interacted very differently with AMV RNA 3' ends. These results suggest that CP dimers are more efficient for replication than CP monomers because of differences in RNA binding rather than differences in expression and accumulation of the mutant CPs in infected cells. PMID:12504539

  15. Importance of anticomplement immunofluorescence antibody titration for diagnosing varicella-zoster virus infection in Bell's palsy.

    Science.gov (United States)

    Shigeta, S; Baba, M; Ogata, M; Nozaki, H; Okuaki, A; Nakamura, S

    1986-11-01

    Anticomplement Immunofluorescence was used for antibody titration against varicella-zoster virus (VZV) in 43 patients with peripheral facial palsy. Nine of 31 patients (29%) with Bell's palsy and eight of 12 patients (75%) with Ramsey-Hunt syndrome had anticomplement immunofluorescence antibody titres of greater than or equal to 1/10. On the other hand, none of 14 patients with herpes simplex virus (HSV) infection and 51 healthy adults showed anticomplement immunofluorescence antibody titres of greater than or equal to 1/10. The anticomplement immunofluorescence antibody titre in two patients with Ramsey-Hunt syndrome increased later and decreased sooner than the indirect immunofluorescence antibody titre, becoming undetectable at 66 and 104 days, respectively, after onset of the disease. There was no cross reaction between anti-VZV and anti-HSV antibodies in the patients who showed a positive antibody rise for VZV. As the acute stage of VZV infection is obscure in the patients with peripheral facial palsy without herpes the screening of anticomplement immunofluorescence antibody to VZV at titres greater than or equal to 1/10 may be useful for the diagnosis of VZV infection in patients with peripheral facial palsy.

  16. Zika virus: Indian perspectives.

    Science.gov (United States)

    Mourya, Devendra T; Shil, Pratip; Sapkal, Gajanan N; Yadav, Pragya D

    2016-05-01

    The emergence of Zika virus (ZiV), a mosquito borne Flavivirus like dengue (DEN) and chikungunya (CHIK), in Brazil in 2014 and its spread to various countries have led to a global health emergency. Aedes aegypti is the major vector for ZiV. Fast dissemination of this virus in different geographical areas posses a major threat especially to regions where the population lacks herd immunity against the ZiV and there is abundance of Aedes mosquitoes. In this review, we focus on current global scenario, epidemiology, biology, diagnostic challenges and remedial measures for ZiVconsidering the Indian perspective. PMID:27487998

  17. Zika virus: Indian perspectives

    Directory of Open Access Journals (Sweden)

    Devendra T Mourya

    2016-01-01

    Full Text Available The emergence of Zika virus (ZiV, a mosquito borne Flavivirus like dengue (DEN and chikungunya (CHIK, in Brazil in 2014 and its spread to various countries have led to a global health emergency. Aedes aegypti is the major vector for ZiV. Fast dissemination of this virus in different geographical areas posses a major threat especially to regions where the population lacks herd immunity against the ZiV and there is abundance of Aedes mosquitoes. In this review, we focus on current global scenario, epidemiology, biology, diagnostic challenges and remedial measures for ZiVconsidering the Indian perspective.

  18. Zika virus: Indian perspectives

    OpenAIRE

    Mourya, Devendra T.; Pratip Shil; Sapkal, Gajanan N.; Yadav, Pragya D

    2016-01-01

    The emergence of Zika virus (ZiV), a mosquito borne Flavivirus like dengue (DEN) and chikungunya (CHIK), in Brazil in 2014 and its spread to various countries have led to a global health emergency. Aedes aegypti is the major vector for ZiV. Fast dissemination of this virus in different geographical areas posses a major threat especially to regions where the population lacks herd immunity against the ZiV and there is abundance of Aedes mosquitoes. In this review, we focus on current global sce...

  19. Zika virus: Indian perspectives

    Science.gov (United States)

    Mourya, Devendra T.; Shil, Pratip; Sapkal, Gajanan N.; Yadav, Pragya D.

    2016-01-01

    The emergence of Zika virus (ZiV), a mosquito borne Flavivirus like dengue (DEN) and chikungunya (CHIK), in Brazil in 2014 and its spread to various countries have led to a global health emergency. Aedes aegypti is the major vector for ZiV. Fast dissemination of this virus in different geographical areas posses a major threat especially to regions where the population lacks herd immunity against the ZiV and there is abundance of Aedes mosquitoes. In this review, we focus on current global scenario, epidemiology, biology, diagnostic challenges and remedial measures for ZiVconsidering the Indian perspective. PMID:27487998

  20. A model for a chikungunya outbreak in a rural Cambodian setting: implications for disease control in uninfected areas.

    Directory of Open Access Journals (Sweden)

    Marguerite Robinson

    2014-09-01

    Full Text Available Following almost 30 years of relative silence, chikungunya fever reemerged in Kenya in 2004. It subsequently spread to the islands of the Indian Ocean, reaching Southeast Asia in 2006. The virus was first detected in Cambodia in 2011 and a large outbreak occurred in the village of Trapeang Roka Kampong Speu Province in March 2012, in which 44% of the villagers had a recent infection biologically confirmed. The epidemic curve was constructed from the number of biologically-confirmed CHIKV cases per day determined from the date of fever onset, which was self-reported during a data collection campaign conducted in the village after the outbreak. All individuals participating in the campaign had infections confirmed by laboratory analysis, allowing for the identification of asymptomatic cases and those with an unreported date of fever onset. We develop a stochastic model explicitly including such cases, all of whom do not appear on the epidemic curve. We estimate the basic reproduction number of the outbreak to be 6.46 (95% C.I. [6.24, 6.78]. We show that this estimate is particularly sensitive to changes in the biting rate and mosquito longevity. Our model also indicates that the infection was more widespread within the population on the reported epidemic start date. We show that the exclusion of asymptomatic cases and cases with undocumented onset dates can lead to an underestimation of the reproduction number which, in turn, could negatively impact control strategies implemented by public health authorities. We highlight the need for properly documenting newly emerging pathogens in immunologically naive populations and the importance of identifying the route of disease introduction.

  1. Chikungunya risk assessment for europe: recommendations for action

    NARCIS (Netherlands)

    Depoortere, E.; Coulombier, D.; Boutin, J.P.; Brooker, S.; Valk, de H.; Dieckmann, S.; Fontenille, D.; Gould, E.; Nathan, M.; Nilsson, M.; Schaffner, F.; Sonnenburg, von F.; Takken, W.

    2006-01-01

    Since March 2005, 255 000 cases of chikungunya fever are estimated to have occurred on the island of Réunion, a French overseas department in the Indian Ocean [1]. An huge increase in estimated cases occurred at the end of December 2005, culminating in an estimated peak incidence of more than 40 000

  2. [Dengue and chikungunya acquired during travel in the tropics

    NARCIS (Netherlands)

    Aart, C.J. van; Braks, M.A.; Hautvast, J.L.A.; Mast, Q. de; Tostmann, A.

    2015-01-01

    - The global incidence of dengue and chikungunya has greatly increased over recent decades, partly due to the increase of geographic distribution of both vectors.- These infections are endemic to the tropics and subtropics, however autochthonous transmission and outbreaks have been described in non-

  3. Importance of Wetlands Management for West Nile Virus Circulation Risk, Camargue, Southern France

    Directory of Open Access Journals (Sweden)

    Sophie Pradier

    2014-08-01

    Full Text Available To assess environmental and horse-level risk factors associated with West Nile Virus (WNV circulation in Camargue, Southern France, a serosurvey was conducted on non-vaccinated horses (n = 1159 from 134 stables in 2007 and 2008. Fifteen Landsat images were examined to quantify areas with open water and flooded vegetation around sampled horses. Mean percentages of areas of open water and flooded vegetation, as well as variations in these percentages between 3 periods (November to February = NOT, March to July = END and August to October = EPI, were calculated for buffers of 2 km radius around the stables. Results of the final logistic regression showed that the risk of WNV seropositivity in horses decreased with their date of acquisition and age. Results also demonstrated the significant role of environmental variables. Horse serological status was associated with variations of open water areas between the NOT (November to February and END (March to July periods, as well as between END and EPI (August to October. WNV spillover was found more intense in areas where water level decreased strongly from winter to spring and from spring to summer.

  4. Cutaneous manifestations in patients suspected of chikungunya disease

    Directory of Open Access Journals (Sweden)

    Prashant Soma

    2009-01-01

    Full Text Available Context : An epidemic of chikungunya disease occurred in India during late 2005 through 2006 affecting nearly 1,400,000 people. Aim : To study the cutaneous manifestations in suspected cases of chikungunya disease. Settings and Design : Patients who attended our outpatient departments from January 2006 to September 2006 were prospectively included if they had symptoms of chikungunya disease according to the ′case definition′ of the National Institute of Communicable Diseases, Directorate General of Health Services, Government of India. The criteria were an acute illness characterized by the sudden onset of fever and several symptoms such as joint pain, headache, backache, photophobia, and eruption during an epidemic of chikungunya fever in the absence of confirmatory serological tests. Materials and Methods : A total of 115 patients (65 men and 50 women who satisfied the above criteria were enrolled for the study. Results : An erythematous maculopapular rash subsiding without any sequelae in 3-4 days was the most common cutaneous finding in our patients. Genital ulcers distributed predominantly over the scrotum and base of the penile shaft in men and labia majora in women were the second most common manifestation. Other manifestations included tenderness/edema of hands and feet, grouped hyperpigmented macules over the nose and cheeks, fixed drug eruptions, erythema nodosum, erythema multiformae, generalized urticarial eruptions, and flare up of pre-existing psoriasis and lichen planus. Conclusions : To conclude, a plethora of cutaneous manifestations were noted in suspected cases of chikungunya disease. Genital ulcers, to the best of our knowledge, have not been reported during the earlier epidemics but have been reported by others during the present one.

  5. Genome-wide analyses of proliferation-important genes of Iridovirus-tiger frog virus by RNAi.

    Science.gov (United States)

    Xie, Jun-Feng; Lai, Yu-Xiong; Huang, Li-Jie; Huang, Run-Qing; Yang, Shao-Wei; Shi, Yan; Weng, Shao-Ping; Zhang, Yong; He, Jian-Guo

    2014-08-30

    Tiger frog virus (TFV), a species of genus Ranavirus in the family Iridoviridae, is a nuclear cytoplasmic large DNA virus that infects aquatic vertebrates such as tiger frog (Rana tigrina rugulosa) and Chinese soft-shelled turtle (Trionyx sinensis). Based on the available genome sequences of TFV, the well-developed RNA interference (RNAi) technique, and the reliable cell line for infection model, we decided to analyze the functional importance of all predicted genes. Firstly, a relative quantitative cytopathogenic effect (Q-CPE) assay was established to monitor the viral proliferation in fish cells. Then, genome-wide RNAi screens of 95 small interference (si) RNAs against TFV were performed to characterize the functional importance of nearly all (95%) predicted TFV genes by Q-CPE scaling system. We identified 32 (33.7%) genes as essential, 50 (52.6%) genes as semi-essential and 13 (13.7%) genes as nonessential for TFV proliferation. Quantitative RT-PCR and titer assays of selected genes were performed to verify the screen results. Furthermore, the screened essential genes were analyzed for their genome distribution and conservative comparison within Ranavirus. Such a systematic screen for viral functional genes by cell phenotypes should provide further insights into understanding of the information in antiviral targets, and in viral replication and pathogenesis of iridovirus. PMID:24886972

  6. DNA vaccine prime and recombinant FPV vaccine boost: an important candidate immunization strategy to control bluetongue virus type 1.

    Science.gov (United States)

    Li, Junping; Yang, Tao; Xu, Qingyuan; Sun, Encheng; Feng, Yufei; Lv, Shuang; Zhang, Qin; Wang, Haixiu; Wu, Donglai

    2015-10-01

    Bluetongue virus (BTV) is the causative agent of bluetongue (BT), an important sheep disease that caused great economic loss to the sheep industry. There are 26 BTV serotypes based on the outer protein VP2. However, the serotypes BTV-1 and BTV-16 are the two most prevalent serotypes in China. Vaccination is the most effective method of preventing viral infections. Therefore, the need for an effective vaccine against BTV is urgent. In this study, DNA vaccines and recombinant fowlpox virus (rFPV) vaccines expressing VP2 alone or VP2 in combination with VP5 or co-expressing the VP2 and VP5 proteins of BTV-1 were evaluated in both mice and sheep. Several strategies were tested in mice, including DNA vaccine prime and boost, rFPV vaccine prime and boost, and DNA vaccine prime and rFPV vaccine boost. We then determined the best vaccine strategy in sheep. Our results indicated that a strategy combining a DNA vaccine prime (co-expressing VP2 and VP5) followed by an rFPV vaccine boost (co-expressing VP2 and VP5) induced a high titer of neutralizing antibodies in sheep. Therefore, our data suggest that a DNA vaccine consisting of a pCAG-(VP2+VP5) prime and an rFPV-(VP2+VP5) boost is an important candidate for the design of a novel vaccine against BTV-1.

  7. Zika Virus: the Latest Newcomer

    OpenAIRE

    Saiz, Juan-Carlos; Vázquez-Calvo, Ángela; Blázquez, Ana B.; Merino-Ramos, Teresa; Escribano-Romero, Estela; Martín-Acebes, Miguel A.

    2016-01-01

    Since the beginning of this century, humanity has been facing a new emerging, or re-emerging, virus threat almost every year: West Nile, Influenza A, avian flu, dengue, Chikungunya, SARS, MERS, Ebola, and now Zika, the latest newcomer. Zika virus (ZIKV), a flavivirus transmitted by Aedes mosquitoes, was identified in 1947 in a sentinel monkey in Uganda, and later on in humans in Nigeria. The virus was mainly confined to the African continent until it was detected in south-east Asia the 1980’s...

  8. Zika virus: the latest newcomer

    OpenAIRE

    Juan-Carlos eSaiz; Angela eVazquez-Calvo; Ana Belen Blazquez; Teresa eMerino-Ramos; Estela eEscribano-Romero; Martín-Acebes, Miguel A.

    2016-01-01

    Since the beginning of this century, humanity has been facing a new emerging, or re-emerging, virus threat almost every year: West Nile, Influenza A, avian flu, dengue, Chikungunya, SARS, MERS, Ebola, and now Zika, the latest newcomer. Zika virus (ZIKV), a flavivirus transmitted by Aedes mosquitoes, was identified in 1947 in a sentinel monkey in Uganda, and later on in humans in Nigeria. The virus was mainly confined to the African continent until it was detected in south-east Asia the 1980´s...

  9. Residual HIV-1 DNA Flap-independent nuclear import of cPPT/CTS double mutant viruses does not support spreading infection

    Directory of Open Access Journals (Sweden)

    Iglesias Candela

    2011-11-01

    Full Text Available Abstract Background The human immunodeficiency virus type 1 (HIV-1 central DNA Flap is generated during reverse transcription as a result of (+ strand initiation at the central polypurine tract (cPPT and termination after a ca. 100 bp strand displacement at the central termination sequence (CTS. The central DNA Flap is a determinant of HIV-1 nuclear import, however, neither cPPT nor CTS mutations entirely abolish nuclear import and infection. Therefore, to determine whether or not the DNA Flap is essential for HIV-1 nuclear import, we generated double mutant (DM viruses, combining cPPT and CTS mutations to abolish DNA Flap formation. Results The combination of cPPT and CTS mutations reduced the proportion of viruses forming the central DNA Flap at the end of reverse transcription and further decreased virus infectivity in one-cycle titration assays. The most affected DM viruses were unable to establish a spreading infection in the highly permissive MT4 cell line, nor in human primary peripheral blood mononuclear cells (PBMCs, indicating that the DNA Flap is required for virus replication. Surprisingly, we found that DM viruses still maintained residual nuclear import levels, amounting to 5-15% of wild-type virus, as assessed by viral DNA circle quantification. Alu-PCR quantification of integrated viral genome also indicated 5-10% residual integration levels compared to wild-type virus. Conclusion This work establishes that the central DNA Flap is required for HIV-1 spreading infection but points to a residual DNA Flap independent nuclear import, whose functional significance remains unclear since it is not sufficient to support viral replication.

  10. Ocular Pathology: Role of Emerging Viruses in the Asia-Pacific Region-A Review.

    Science.gov (United States)

    Ranjan, Ratnesh; Ranjan, Shikha

    2014-01-01

    The role of viral infections in ocular pathology varies greatly, involving all the components of the eye. Some viruses like herpes simplex, herpes zoster, adenovirus, enterovirus 70, influenza virus, human immunodeficiency virus, and cytomegalovirus are well-known for their role in ocular pathology. In recent years, emerging and resurging viral infections represent an important public health problem. The Asia-Pacific region has witnessed a number of pandemic and epidemic outbreaks caused by these viruses during the last 2 decades. The number of ocular complications being reported in patients of these viral infections has also increased significantly during this period. Ophthalmologists and physicians should be aware of ocular manifestations of newly emerging or resurging viral diseases. We conducted a review of the literature published during the last 20 years with the objectives of finding out outbreaks of emerging and reemerging viruses in the Asia-Pacific region and finding out any ocular involvement in these viral infections. An iterative search of the MEDLINE and the Google databases was made using the search terms emerging virus, ocular manifestations, ocular complications, Chikungunya, Dengue, Japanese encephalitis, West Nile fever, Kyasanur forest disease, Rift valley fever, Hantavirus, Henipavirus, Influenza virus, Enterovirus 71, and Asia-Pacific region, separately and with reported ocular involvement in combination. This review article discusses the epidemiology and the systemic and ocular manifestations of all emerging viral infections with reported ocular involvement in the Asia-Pacific region. PMID:26107917

  11. Effect of Mosquito Repellent on the Transmission Model of Chikungunya Fever

    OpenAIRE

    Surapol Naowarat; Prasit Thongjaem; Tang, I. M.

    2012-01-01

    Problem statement: In 2008 there was a large outbreak of Chikungunya fever in southern Thailand. Chikungunya fever is an emerging disease which tends to affect rubber plantation and fruit orchard workers more than other occupation. This study we considers the efficacy of using mosquito repellent as a way to prevent and control the spread of Chikungunya fever. The mathematical model of the dynamic of this disease is proposed and analyzed. Approach: A standard dynamical modeling method was appl...

  12. Zika Virus: Diagnostics for an Emerging Pandemic Threat

    Science.gov (United States)

    Waggoner, Jesse J.

    2016-01-01

    Zika virus (ZIKV) is an Aedes mosquito-borne flavivirus that emerged in Brazil in 2015 and then rapidly spread throughout the tropical and subtropical Americas. Based on clinical criteria alone, ZIKV cannot be reliably distinguished from infections with other pathogens that cause an undifferentiated systemic febrile illness, including infections with two common arboviruses, dengue virus and chikungunya virus. This minireview details the methods that are available to diagnose ZIKV infection. PMID:26888897

  13. A single mutation in the E2 glycoprotein important for neurovirulence influences binding of Sindbis virus to neuroblastoma cells

    NARCIS (Netherlands)

    Lee, PY; Knight, R; Smit, JM; Wilschut, J; Griffin, DE

    2002-01-01

    The amino acid at position 55 of the E2 glycoprotein (E2(55)) of Sindbis virus (SV) is a critical determinant of SV neurovirulence in mice. Recombinant virus strain TE (E2(55) = histidine) differs only at this position from virus strain 633 (E2(55) = glutamine), yet TE is considerably more neuroviru

  14. Positive-Strand RNA Viruses Infecting the Red Imported Fire Ant, Solenopsis invicta

    OpenAIRE

    Valles, Steven M.

    2012-01-01

    The imported fire ants, Solenopsis invicta and S. richteri were introduced into the USA between 1918 and 1945. Since that time, they have expanded their USA range to include some 138 million hectares. Their introduction has had significant economic consequences with costs associated with damage and control efforts estimated at 6 billion dollars annually in the USA. The general consensus of entomologists and myrmecologists is that permanent, sustainable control of these ants in the USA will li...

  15. Reduced Risk of Importing Ebola Virus Disease because of Travel Restrictions in 2014: A Retrospective Epidemiological Modeling Study

    Science.gov (United States)

    Otsuki, Shiori

    2016-01-01

    Background An epidemic of Ebola virus disease (EVD) from 2013–16 posed a serious risk of global spread during its early growth phase. A post-epidemic evaluation of the effectiveness of travel restrictions has yet to be conducted. The present study aimed to estimate the effectiveness of travel restrictions in reducing the risk of importation from mid-August to September, 2014, using a simple hazard-based statistical model. Methodology/Principal Findings The hazard rate was modeled as an inverse function of the effective distance, an excellent predictor of disease spread, which was calculated from the airline transportation network. By analyzing datasets of the date of EVD case importation from the 15th of July to the 15th of September 2014, and assuming that the network structure changed from the 8th of August 2014 because of travel restrictions, parameters that characterized the hazard rate were estimated. The absolute risk reduction and relative risk reductions due to travel restrictions were estimated to be less than 1% and about 20%, respectively, for all models tested. Effectiveness estimates among African countries were greater than those for other countries outside Africa. Conclusions The travel restrictions were not effective enough to expect the prevention of global spread of Ebola virus disease. It is more efficient to control the spread of disease locally during an early phase of an epidemic than to attempt to control the epidemic at international borders. Capacity building for local containment and coordinated and expedited international cooperation are essential to reduce the risk of global transmission. PMID:27657544

  16. The Emergence of Zika Virus: A Narrative Review.

    Science.gov (United States)

    Anderson, Kathryn B; Thomas, Stephen J; Endy, Timothy P

    2016-08-01

    Zika virus (ZIKV) is yet another arbovirus that is rapidly emerging on a global scale, on the heels of a chikungunya epidemic in the Americas that began in 2013. A ZIKV epidemic that began in Brazil in 2015 has now spread rapidly to more than 30 countries in the Americas and the Caribbean, infecting more than 2 million inhabitants. This epidemic currently continues unabated. The explosive nature of recent outbreaks and concerning links to Guillain-Barré syndrome and microcephaly are incompletely understood. Also unknown is the relative importance of sexual transmission of ZIKV and asymptomatic ZIKV infections to the overall burden of transmission. The limited understanding of ZIKV presents an enormous challenge for responses to this rapidly emerging threat to human health. This article reviews the existing literature on ZIKV and proposes critical questions for vaccine development and other areas of needed research. PMID:27135717

  17. High Dose Intraveneous Vitamin C and Chikungunya Fever: A Case Report

    Science.gov (United States)

    Gonzalez, Michael J.; Miranda-Massari, Jorge R.; Berdiel, Miguel J.; Duconge, Jorge; Rodríguez-López, Joshua L.; Hunninghake, Ron; Cobas-Rosario, Vicente J.

    2015-01-01

    The Chikungunya (CHIKV) fever is a viral disease produced by a single-stranded RNA Alphavirus from the Togaviridae genus. Its transmission occurs only through mosquito vectors, principally Aedes aegypti. It requires a human-mosquito-human transmission cycle. It is associated with severe arthritis/arthralgias, myalgias, high fever, headache, and maculopapular rash. Joint ache appears to be symmetrical. The virus has an incubation period of 2 to 7 days, where the high fever is typically presented. It is followed by arthralgias and myalgias, and rashes, which last for 3 to 5 days. However, the arthralgias can persist for months after the infection, which can contribute to severe arthritis. As of now, no vaccine exists for the virus and no official treatment has been developed aside from standard procedures of the use of acetaminophen (paracetamol), and non-steroidal anti-inflammatory drugs. This is a case report of a 54-year old Hispanic individual that reported left shoulder pain, left knee pain and fever. The symptoms started on a Saturday in September 2014 in middle of the night. The patient was treated with high doses of intravenous vitamin C over two days. The symptoms resolved after the infusions without any side effects. Based on the positive outcome in this case, we propose that intravenous vitamin C should be studied further as a potential treatment for acute viral infections. PMID:25705076

  18. Chikungunya fever: Atypical and lethal cases in the Western hemisphere

    Science.gov (United States)

    Torres, Jaime R.; Leopoldo Códova G.; Castro, Julio S.; Rodríguez, Libsen; Saravia, Víctor; Arvelaez, Joanne; Ríos-Fabra, Antonio; Longhi, María A.; Marcano, Melania

    2014-01-01

    A large epidemic of Chikungunya fever currently affects the Caribbean, Central and South America. Despite a high number of reported cases, little is known on the occurrence of severe clinical complications. We describe four Venezuelan patients with a severe and/or lethal course who exhibit unusual manifestations of the disease. Case 1 describes a 75 year-old man with rapid onset of septic shock and multi-organ failure. Cases 2 and 3 describe two patients with rapid aggressive clinical course who developed shock, severe purpuric lesions and a distinct area large of necrosis in the nasal region. Case 4 depicts a splenectomized woman with shock, generalized purpuric lesions, bullous dermatosis and acronecrosis of an upper limb. Chikungunya fever in the Western hemisphere may also associate with atypical and severe manifestations. Some patients experience a life-threatening, aggressive clinical course, with rapid deterioration and death due to multisystem failure. PMID:26793440

  19. Epidemiological investigations of chikungunya epidemic at Barsi, Maharashtra state, India.

    Science.gov (United States)

    Padbidri, V S; Gnaneswar, T T

    1979-01-01

    During the summer of 1973, an epidemic of Chikungunya broke out in Barsi, Sholapur district. Epidemiological investigations carried out during the decline phase revealed that all age groups and both sexes were involved with varying morbidity. The absence of previous immunity was demonstrated by a very high morbidity of 37.53 per cent for the whole town. The clinical picture encountered during the epidemic was quite characteristic of chikungunya. Besides gingivitis and epistaxis there were no frank haemorrhagic episodes. Reports about the presence of demonstrable rash varied. Except for one possible case, there was no mortality as a result of the epidemic. Results of the search for the index case are also described.

  20. Molecular determinants of dengue virus 2 envelope protein important for virus entry in FcγRIIA-mediated antibody-dependent enhancement of infection

    International Nuclear Information System (INIS)

    Antibody-dependent enhancement (ADE) of infection may cause severe illness in patients suffering a secondary infection by a heterologous dengue virus (DENV) serotype. During ADE of infection, cross-reactive non- or poorly-neutralizing antibodies form infectious virus-Ab complexes with the newly infecting serotype and enhance virus infection by binding to the Fcγ receptors (FcγR) on FcγR-bearing cells. In this study, we determined that molecular determinants of DENV2 envelope protein critical for virus entry during non-ADE infection are also required for ADE infection mediated by FcγRIIA, and binding of virus-Ab complexes with FcγRIIA alone is not sufficient for ADE of infection. The FcγRIIA mainly plays an auxiliary role in concentrating the virus–Ab complex to the cell surface, and other primary cellular receptors are required for virus entry. Understanding the viral entry pathway in ADE of DENV infection will greatly facilitate rational designs of anti-viral therapeutics against severe dengue disease associated with ADE. - Highlights: • KKK305/307/310 in DENV2 E-DIII is critical for virus attachment in ADE and non-ADE infection. • Binding of DENV2–Ab complex with FcγRII alone is not sufficient for virus entry in ADE infection. • Other primary receptors were required for DENV2 internalization during FcγRII–mediated ADE. • G104 and L135 of DENV2 E are critical for virus-mediated membrane fusion. • DENV2 virus-mediated membrane fusion is required for both ADE and non-ADE infection

  1. Molecular determinants of dengue virus 2 envelope protein important for virus entry in FcγRIIA-mediated antibody-dependent enhancement of infection

    Energy Technology Data Exchange (ETDEWEB)

    Chotiwan, Nunya; Roehrig, John T. [Arboviral Diseases Branch, Division of Vector-Borne Disease, Centers for Disease Control and Prevention, Fort Collins, CO 80521 (United States); Schlesinger, Jacob J. [Department of Medicine, University of Rochester, Rochester, NY 14642 (United States); Blair, Carol D. [Arthropod-borne and Infectious Diseases Laboratory, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80523 (United States); Huang, Claire Y.-H., E-mail: yxh0@cdc.gov [Arboviral Diseases Branch, Division of Vector-Borne Disease, Centers for Disease Control and Prevention, Fort Collins, CO 80521 (United States)

    2014-05-15

    Antibody-dependent enhancement (ADE) of infection may cause severe illness in patients suffering a secondary infection by a heterologous dengue virus (DENV) serotype. During ADE of infection, cross-reactive non- or poorly-neutralizing antibodies form infectious virus-Ab complexes with the newly infecting serotype and enhance virus infection by binding to the Fcγ receptors (FcγR) on FcγR-bearing cells. In this study, we determined that molecular determinants of DENV2 envelope protein critical for virus entry during non-ADE infection are also required for ADE infection mediated by FcγRIIA, and binding of virus-Ab complexes with FcγRIIA alone is not sufficient for ADE of infection. The FcγRIIA mainly plays an auxiliary role in concentrating the virus–Ab complex to the cell surface, and other primary cellular receptors are required for virus entry. Understanding the viral entry pathway in ADE of DENV infection will greatly facilitate rational designs of anti-viral therapeutics against severe dengue disease associated with ADE. - Highlights: • KKK305/307/310 in DENV2 E-DIII is critical for virus attachment in ADE and non-ADE infection. • Binding of DENV2–Ab complex with FcγRII alone is not sufficient for virus entry in ADE infection. • Other primary receptors were required for DENV2 internalization during FcγRII–mediated ADE. • G104 and L135 of DENV2 E are critical for virus-mediated membrane fusion. • DENV2 virus-mediated membrane fusion is required for both ADE and non-ADE infection.

  2. A propósito de un caso de Fiebre de Chikungunya importada de América

    Directory of Open Access Journals (Sweden)

    F.J. Membrillo de Novales

    2015-09-01

    Full Text Available Presentamos el caso de un varón de 41 años que tras viajar como VFR (Visiting Friends and Relatives a Valencia, Venezuela, presentó a su regreso a España un cuadro de fiebre y artromialgias. El paciente cumplía criterios clínicos para el diagnosticado de fiebre de Chikungunya, recientemente introducida en América y donde se desarrolla en la actualidad una epidemia que afecta al país que viajó. El estudio serológico por el laboratorio de referencia confirmó esta sospecha al detectar IgM frente a virus Chikungunya (CHIKV. Al tratarse de una arbovirosis poco conocida en nuestro medio y de interés militar, aprovechamos el caso, primero diagnosticado en nuestro Hospital en el contexto de esta epidemia, para revisar la situación de esta enfermedad y la epidemiología del brote actual.

  3. Feline leukemia virus and other pathogens as important threats to the survival of the critically endangered Iberian lynx (Lynx pardinus.

    Directory of Open Access Journals (Sweden)

    Marina L Meli

    Full Text Available BACKGROUND: The Iberian lynx (Lynx pardinus is considered the most endangered felid species in the world. In order to save this species, the Spanish authorities implemented a captive breeding program recruiting lynxes from the wild. In this context, a retrospective survey on prevalence of selected feline pathogens in free-ranging lynxes was initiated. METHODOLOGY/ PRINCIPAL FINDINGS: We systematically analyzed the prevalence and importance of seven viral, one protozoan (Cytauxzoon felis, and several bacterial (e.g., hemotropic mycoplasma infections in 77 of approximately 200 remaining free-ranging Iberian lynxes of the Doñana and Sierra Morena areas, in Southern Spain, between 2003 and 2007. With the exception of feline immunodeficiency virus (FIV, evidence of infection by all tested feline pathogens was found in Iberian lynxes. Fourteen lynxes were feline leukemia virus (FeLV provirus-positive; eleven of these were antigenemic (FeLV p27 positive. All 14 animals tested negative for other viral infections. During a six-month period in 2007, six of the provirus-positive antigenemic lynxes died. Infection with FeLV but not with other infectious agents was associated with mortality (p<0.001. Sequencing of the FeLV surface glycoprotein gene revealed a common origin for ten of the eleven samples. The ten sequences were closely related to FeLV-A/61E, originally isolated from cats in the USA. Endogenous FeLV sequences were not detected. CONCLUSIONS/SIGNIFICANCE: It was concluded that the FeLV infection most likely originated from domestic cats invading the lynx's habitats. Data available regarding the time frame, co-infections, and outcome of FeLV-infections suggest that, in contrast to the domestic cat, the FeLV strain affecting the lynxes in 2007 is highly virulent to this species. Our data argue strongly for vaccination of lynxes and domestic cats in and around lynx's habitats in order to prevent further spread of the virus as well as reduction the

  4. Interactions of Prototype Foamy Virus Capsids with Host Cell Polo-Like Kinases Are Important for Efficient Viral DNA Integration.

    Science.gov (United States)

    Zurnic, Irena; Hütter, Sylvia; Rzeha, Ute; Stanke, Nicole; Reh, Juliane; Müllers, Erik; Hamann, Martin V; Kern, Tobias; Gerresheim, Gesche K; Lindel, Fabian; Serrao, Erik; Lesbats, Paul; Engelman, Alan N; Cherepanov, Peter; Lindemann, Dirk

    2016-08-01

    Unlike for other retroviruses, only a few host cell factors that aid the replication of foamy viruses (FVs) via interaction with viral structural components are known. Using a yeast-two-hybrid (Y2H) screen with prototype FV (PFV) Gag protein as bait we identified human polo-like kinase 2 (hPLK2), a member of cell cycle regulatory kinases, as a new interactor of PFV capsids. Further Y2H studies confirmed interaction of PFV Gag with several PLKs of both human and rat origin. A consensus Ser-Thr/Ser-Pro (S-T/S-P) motif in Gag, which is conserved among primate FVs and phosphorylated in PFV virions, was essential for recognition by PLKs. In the case of rat PLK2, functional kinase and polo-box domains were required for interaction with PFV Gag. Fluorescently-tagged PFV Gag, through its chromatin tethering function, selectively relocalized ectopically expressed eGFP-tagged PLK proteins to mitotic chromosomes in a Gag STP motif-dependent manner, confirming a specific and dominant nature of the Gag-PLK interaction in mammalian cells. The functional relevance of the Gag-PLK interaction was examined in the context of replication-competent FVs and single-round PFV vectors. Although STP motif mutated viruses displayed wild type (wt) particle release, RNA packaging and intra-particle reverse transcription, their replication capacity was decreased 3-fold in single-cycle infections, and up to 20-fold in spreading infections over an extended time period. Strikingly similar defects were observed when cells infected with single-round wt Gag PFV vectors were treated with a pan PLK inhibitor. Analysis of entry kinetics of the mutant viruses indicated a post-fusion defect resulting in delayed and reduced integration, which was accompanied with an enhanced preference to integrate into heterochromatin. We conclude that interaction between PFV Gag and cellular PLK proteins is important for early replication steps of PFV within host cells. PMID:27579920

  5. Interactions of Prototype Foamy Virus Capsids with Host Cell Polo-Like Kinases Are Important for Efficient Viral DNA Integration

    Science.gov (United States)

    Zurnic, Irena; Hütter, Sylvia; Rzeha, Ute; Stanke, Nicole; Reh, Juliane; Müllers, Erik; Hamann, Martin V.; Kern, Tobias; Gerresheim, Gesche K.; Serrao, Erik; Lesbats, Paul; Engelman, Alan N.; Cherepanov, Peter; Lindemann, Dirk

    2016-01-01

    Unlike for other retroviruses, only a few host cell factors that aid the replication of foamy viruses (FVs) via interaction with viral structural components are known. Using a yeast-two-hybrid (Y2H) screen with prototype FV (PFV) Gag protein as bait we identified human polo-like kinase 2 (hPLK2), a member of cell cycle regulatory kinases, as a new interactor of PFV capsids. Further Y2H studies confirmed interaction of PFV Gag with several PLKs of both human and rat origin. A consensus Ser-Thr/Ser-Pro (S-T/S-P) motif in Gag, which is conserved among primate FVs and phosphorylated in PFV virions, was essential for recognition by PLKs. In the case of rat PLK2, functional kinase and polo-box domains were required for interaction with PFV Gag. Fluorescently-tagged PFV Gag, through its chromatin tethering function, selectively relocalized ectopically expressed eGFP-tagged PLK proteins to mitotic chromosomes in a Gag STP motif-dependent manner, confirming a specific and dominant nature of the Gag-PLK interaction in mammalian cells. The functional relevance of the Gag-PLK interaction was examined in the context of replication-competent FVs and single-round PFV vectors. Although STP motif mutated viruses displayed wild type (wt) particle release, RNA packaging and intra-particle reverse transcription, their replication capacity was decreased 3-fold in single-cycle infections, and up to 20-fold in spreading infections over an extended time period. Strikingly similar defects were observed when cells infected with single-round wt Gag PFV vectors were treated with a pan PLK inhibitor. Analysis of entry kinetics of the mutant viruses indicated a post-fusion defect resulting in delayed and reduced integration, which was accompanied with an enhanced preference to integrate into heterochromatin. We conclude that interaction between PFV Gag and cellular PLK proteins is important for early replication steps of PFV within host cells. PMID:27579920

  6. Virus-encoded miR-155 ortholog is an important potential regulator but not essential for the development of lymphomas induced by very virulent Marek's disease virus.

    Science.gov (United States)

    Yu, Zu-Hua; Teng, Man; Sun, Ai-Jun; Yu, Le-Le; Hu, Bo; Qu, Liang-Hu; Ding, Ke; Cheng, Xiang-Chao; Liu, Ju-Xiong; Cui, Zhi-Zhong; Zhang, Gai-Ping; Luo, Jun

    2014-01-01

    The microRNA (miRNA) mdv1-miR-M4, a functional miR-155 ortholog encoded by oncogenic Marek's disease virus (MDV), has previously been suggested to be involved in MDV pathogenesis. Using the technique of bacterial artificial chromosome mutagenesis, we have presently evaluated the potential role of mdv1-miR-M4 in the oncogenesis of the very virulent (vv) MDV strain GX0101. Unexpectedly, deletions of the Meq-cluster or mdv1-miR-M4 alone from the viral genome strongly decreased rather than abolished its oncogenicity. Compared to GX0101, mortalities of mutants GXΔmiR-M4 and GXΔMeq-miRs were reduced from 100% to 18% and 4%, coupled with the gross tumor incidence reduction from 28% to 22% and 8%, respectively. Our data suggests that the mdv1-miR-M4 is possibly an important regulator in the development of Marek's disease (MD) lymphomas but is not essential for the oncogenicity of vvMDV. In addition, some of the other Meq-clustered miRNAs may also play potentially critical roles in vvMDV induction of lymphomas. PMID:24314636

  7. An Epstein-Barr virus encoded inhibitor of Colony Stimulating Factor-1 signaling is an important determinant for acute and persistent EBV infection.

    Directory of Open Access Journals (Sweden)

    Makoto Ohashi

    2012-12-01

    Full Text Available Acute Epstein-Barr virus (EBV infection is the most common cause of Infectious Mononucleosis. Nearly all adult humans harbor life-long, persistent EBV infection which can lead to development of cancers including Hodgkin Lymphoma, Burkitt Lymphoma, nasopharyngeal carcinoma, gastric carcinoma, and lymphomas in immunosuppressed patients. BARF1 is an EBV replication-associated, secreted protein that blocks Colony Stimulating Factor 1 (CSF-1 signaling, an innate immunity pathway not targeted by any other virus species. To evaluate effects of BARF1 in acute and persistent infection, we mutated the BARF1 homologue in the EBV-related herpesvirus, or lymphocryptovirus (LCV, naturally infecting rhesus macaques to create a recombinant rhLCV incapable of blocking CSF-1 (ΔrhBARF1. Rhesus macaques orally challenged with ΔrhBARF1 had decreased viral load indicating that CSF-1 is important for acute virus infection. Surprisingly, ΔrhBARF1 was also associated with dramatically lower virus setpoints during persistent infection. Normal acute viral load and normal viral setpoints during persistent rhLCV infection could be restored by Simian/Human Immunodeficiency Virus-induced immunosuppression prior to oral inoculation with ΔrhBARF1 or infection of immunocompetent animals with a recombinant rhLCV where the rhBARF1 was repaired. These results indicate that BARF1 blockade of CSF-1 signaling is an important immune evasion strategy for efficient acute EBV infection and a significant determinant for virus setpoint during persistent EBV infection.

  8. Chikungunya: acute fever, rash and debilitating arthralgias in a returning traveler from Haiti.

    Science.gov (United States)

    Anderson, Kathryn B; Pureza, Vincent; Walker, Patricia F

    2014-01-01

    The following case report details a case of chikungunya fever in a returning traveler from Haiti. The report highlights the clinical presentation and natural history of the disease, and emphasizes that chikungunya has become established in the western hemisphere, with a resultant need for heightened provider awareness.

  9. Complete Genome Sequence of an Ebola Virus Isolate Imported from Sierra Leone to Germany Determined by Circle Sequencing

    Science.gov (United States)

    Mengel, Jan Philipp; Lissin, Artur; Biedenkopf, Nadine; Schultze, Tilman; Mannala, Gopala Krishna; Schudt, Gordian; Kann, Gerrit; Wolf, Timo; Eickmann, Markus; Becker, Stephan

    2016-01-01

    We report here a complete genome sequence of Ebola virus Makona from a nonfatal patient sample that originated in Sierra Leone during the last Ebola virus outbreak in West Africa (species Zaire ebolavirus) using a highly accurate circle sequencing (Cir-seq) method.

  10. The high susceptibility of turkeys to influenza viruses of different origins implies their importance as potential intermediate hosts.

    Science.gov (United States)

    Pillai, S P S; Pantin-Jackwood, M; Yassine, H M; Saif, Y M; Lee, C W

    2010-03-01

    Several previous reports and our studies show that waterfowl-origin influenza viruses can be more easily transmitted to domestic turkeys than chickens. Similarly, studies indicate turkeys to be better hosts for low pathogenic avian influenza viruses isolated from commercial poultry operations and live bird markets in comparison to chickens. Low 50% infectious-dose titers of wild bird as well as poultry-adapted viruses for turkeys further suggest that turkeys can be easily infected following a low-dose exposure. Also, interspecies transmission of swine influenza viruses to turkeys occurs frequently. These findings suggest the role of turkeys as suitable intermediate hosts that can be easily infected with influenza viruses of different origins and that turkeys can act as source of infection for other land-based poultry or even mammals. PMID:20521688

  11. Reconstruction of 60 Years of Chikungunya Epidemiology in the Philippines Demonstrates Episodic and Focal Transmission.

    Science.gov (United States)

    Salje, Henrik; Cauchemez, Simon; Alera, Maria Theresa; Rodriguez-Barraquer, Isabel; Thaisomboonsuk, Butsaya; Srikiatkhachorn, Anon; Lago, Catherine B; Villa, Daisy; Klungthong, Chonticha; Tac-An, Ilya A; Fernandez, Stefan; Velasco, John Mark; Roque, Vito G; Nisalak, Ananda; Macareo, Louis R; Levy, Jens W; Cummings, Derek; Yoon, In-Kyu

    2016-02-15

    Proper understanding of the long-term epidemiology of chikungunya has been hampered by poor surveillance. Outbreak years are unpredictable and cases often misdiagnosed. Here we analyzed age-specific data from 2 serological studies (from 1973 and 2012) in Cebu, Philippines, to reconstruct both the annual probability of infection and population-level immunity over a 60-year period (1952-2012). We also explored whether seroconversions during 2012-2013 were spatially clustered. Our models identified 4 discrete outbreaks separated by an average delay of 17 years. On average, 23% (95% confidence interval [CI], 16%-37%) of the susceptible population was infected per outbreak, with >50% of the entire population remaining susceptible at any point. Participants who seroconverted during 2012-2013 were clustered at distances of 350 000 infections were missed by surveillance systems. Serological studies could supplement surveillance to provide important insights on pathogen circulation.

  12. Hemolymph cells apoptosis in imported shrimp Litopenaeus vannamei from Hawaii to Iran, exposed to white spot virus

    Institute of Scientific and Technical Information of China (English)

    Zeliha Selamoglu Talas; Mehmet Fuat Gulhan

    2014-01-01

    Objective: To show hemolymph apoptosis in imported shrimp Litopenaeus vannamei from Hawaii to Iran. Methods: One hundred and eighty shrimps [(7.98±0.54) g] which were collected from a research shrimp farm located in Heleh site in north of Bushehr Province were distributed equally to 6 glass aquariums (50 cmí50 cmí60 cm) as group A in triplicate (imported batch in 2011, without crossing with other generations) with well clean aerated sea water (100 L per aquarium), salinity of 40 ‰ and temperature of 29 °C. Shrimps of group B (produced by crossing the adults of imported batches in 2009 up to 2011) were distributed also among 6 aquariums with the same conditions. Both shrimp groups were injected with concentration of LD50=1í105.4 white spot virus.Results:exposure and reached 100% after 36 h but no mortality was occurred up to 15 d in shrimps of group B. The slide evaluation of hemolymph of group B showed an increasing trend of apoptosis occurrence in all three types of hemolymph cells, hyalinocytes, semi-granulocytes and granulocytes from 24 h to 72 h in contrary to group A that not any apoptosis was observed during the course of the study (15 d). The results showed that in group A, the mortality began approximately 24 h after Conclusions: It is concluded that crossing among the specific pathogen free generations could induce the increasing immunity level through apoptosis to protect them against white spot disease.

  13. High temporal and spatial diversity in marine RNA viruses implies that they have an important role in mortality and structuring plankton communities

    Directory of Open Access Journals (Sweden)

    Julia Anne Gustavsen

    2014-12-01

    Full Text Available Viruses in the order Picornavirales infect eukaryotes, and are widely distributed in coastal waters. Amplicon deep-sequencing of the RNA dependent RNA polymerase (RdRp revealed diverse and highly uneven communities of picorna-like viruses in the coastal waters of British Columbia (B.C., Canada. Almost 300 000 pyrosequence reads revealed 145 operational taxonomic units (OTUs based on 95% sequence similarity at the amino-acid level. Each sample had between 24 and 71 OTUs and there was little overlap among samples. Phylogenetic analysis revealed that some clades of OTUs were only found at one site; whereas, other groups included OTUs from all sites. Since most of these OTUs are likely from viruses that infect eukaryotic phytoplankton, and viral isolates infecting phytoplankton are strain-specific; each OTU probably arose from the lysis of a specific phytoplankton taxon. Moreover, the patchiness in OTU distribution, and the high turnover of viruses in the mixed layer, implies continuous infection and lysis by RNA viruses of a diverse array of eukaryotic phytoplankton taxa. Hence, these viruses are likely important elements structuring the phytoplankton community, and play a significant role in nutrient cycling and energy transfer.

  14. Projected Zika Virus Importation and Subsequent Ongoing Transmission after Travel to the 2016 Olympic and Paralympic Games - Country-Specific Assessment, July 2016.

    Science.gov (United States)

    Grills, Ardath; Morrison, Stephanie; Nelson, Bradley; Miniota, Jennifer; Watts, Alexander; Cetron, Martin S

    2016-01-01

    Zika virus belongs to the genus Flavivirus of the family Flaviviridae; it is transmitted to humans primarily through the bite of an infected Aedes species mosquito (e.g., Ae. aegypti and Ae. albopictus) (1). Zika virus has been identified as a cause of congenital microcephaly and other serious brain defects (2). As of June 30, 2016, CDC had issued travel notices for 49 countries and U.S. territories across much of the Western hemisphere (3), including Brazil, where the 2016 Olympic and Paralympic Games (Games of the XXXI Olympiad, also known as Rio 2016; Games) will be hosted in Rio de Janeiro in August and September 2016. During the Games, mosquito-borne Zika virus transmission is expected to be low because August and September are winter months in Brazil, when cooler and drier weather typically reduces mosquito populations (4). CDC conducted a risk assessment to predict those countries susceptible to ongoing Zika virus transmission resulting from introduction by a single traveler to the Games. Whereas all countries are at risk for travel-associated importation of Zika virus, CDC estimated that 19 countries currently not reporting Zika outbreaks have the environmental conditions and population susceptibility to sustain mosquito-borne transmission of Zika virus if a case were imported from infection at the Games. For 15 of these 19 countries, travel to Rio de Janeiro during the Games is not estimated to increase substantially the level of risk above that incurred by the usual aviation travel baseline for these countries. The remaining four countries, Chad, Djibouti, Eritrea, and Yemen, are unique in that they do not have a substantial number of travelers to any country with local Zika virus transmission, except for anticipated travel to the Games. These four countries will be represented by a projected, combined total of 19 athletes (plus a projected delegation of about 60 persons), a tiny fraction of the 350,000-500,000 visitors expected at the Games.* Overall

  15. Importância, problemas e perspectivas do melhoramento visando resistência a viroses em plantas Importance, problems and perspectives of plant breeding concerning resistance to viruses

    Directory of Open Access Journals (Sweden)

    Rosa Lia Barbieri

    1995-01-01

    Full Text Available As viroses são um sério problema para a agricultura, podendo se tomar um fator limitante para o desenvolvimento de determinadas espécies. Medidas de controle, como a eliminação dos vetores, o uso de material sadio, a rotação de culturas e a erradicação de plantas infectadas são apenas soluções temporárias. A mais eficiente estratégia de controle envolve o uso de cultivares melhoradas para resistência ao vírus ou a seu vetor. A reduzida disponibilidade de fontes de resistência pode ser aumentada através da tecnologia do DNA recombinante, que traz novas perspectivas para o melhoramento de plantas resistentes a viroses.Virus diseases are a serious problem to agricuiture, can be a limitant factor to normal development of some crops. Control measures, like vectors elimination, healthy material use, culture rotation and infected plants eradication, are only transient solutions. The more efficient approach for control involves plant breeding resistant to virus or its vector. Reduced availability of resistance source can be increased through recombinant DNA technology, which brings new breeding perspectives to virus resistant crops.

  16. Evaluation of multiple antigenic peptides based on the Chikungunya E2 protein for improved serological diagnosis of infection.

    Science.gov (United States)

    Bhatnagar, Santwana; Kumar, Pradeep; Mohan, Teena; Verma, Priyanka; Parida, M M; Hoti, S L; Rao, D N

    2015-03-01

    In recent years, Chikungunya virus (CHIKV) reemerged and numerous outbreaks were reported all over the world. After screening CHIKV-positive sera, we had already reported many dominant epitopes within the envelope E2 protein of CHIKV. In the present study, we aimed at developing a highly sensitive immunodiagnostic assay for CHIKV based on a multiple antigenic peptide (MAP) approach using selective epitopes of the E2 protein. MAPs in four different E2 peptide combinations were screened with CHIKV-positive sera. The MAPs reacted with all CHIKV-positive sera and no reactivity was seen with healthy or dengue-positive sera. Our results indicate that MAP 1 seems to be an alternate antigen to full-length protein E2 for immunodiagnosis of CHIKV infections with high sensitivity and specificity. PMID:25412351

  17. Extended Preclinical Safety, Efficacy and Stability Testing of a Live-attenuated Chikungunya Vaccine Candidate.

    Directory of Open Access Journals (Sweden)

    Kenneth S Plante

    Full Text Available We recently described a new, live-attenuated vaccine candidate for chikungunya (CHIK fever, CHIKV/IRES. This vaccine was shown to be well attenuated, immunogenic and efficacious in protecting against CHIK virus (CHIKV challenge of mice and nonhuman primates. To further evaluate its preclinical safety, we compared CHIKV/IRES distribution and viral loads in interferon-α/β receptor-incompetent A129 mice to another CHIK vaccine candidate, 181/clone25, which proved highly immunogenic but mildly reactive in human Phase I/II clinical trials. Compared to wild-type CHIK virus, (wt-CHIKV, both vaccines generated lower viral loads in a wide variety of tissues and organs, including the brain and leg muscle, but CHIKV/IRES exhibited marked restrictions in dissemination and viral loads compared to 181/clone25, and was never found outside the blood, spleen and muscle. Unlike wt-CHIKV, which caused disrupted splenic architecture and hepatic lesions, histopathological lesions were not observed in animals infected with either vaccine strain. To examine the stability of attenuation, both vaccines were passaged 5 times intracranially in infant A129 mice, then assessed for changes in virulence by comparing parental and passaged viruses for footpad swelling, weight stability and survival after subcutaneous infection. Whereas strain 181/clone25 p5 underwent a significant increase in virulence as measured by weight loss (from 30% and mortality (from 0 to 100%, CHIKV/IRES underwent no detectible change in any measure of virulence (no significant weight loss and no mortality. These data indicate greater nonclinical safety of the CHIKV/IRES vaccine candidate compared to 181/clone25, further supporting its eligibility for human testing.

  18. Mutagenesis analysis of the murine leukemia virus matrix protein: identification of regions important for membrane localization and intracellular transport.

    Science.gov (United States)

    Soneoka, Y; Kingsman, S M; Kingsman, A J

    1997-07-01

    We have created two sets of substitution mutations in the Moloney murine leukemia virus (Mo-MuLV) matrix protein in order to identify domains involved in association with the plasma membrane and in incorporation of the viral envelope glycoproteins into virus particles. The first set of mutations was targeted at putative membrane-associating regions similar to those of the human immunodeficiency virus type 1 matrix protein, which include a polybasic region at the N terminus of the Mo-MuLV matrix protein and two regions predicted to form beta strands. The second set of mutations was created within hydrophobic residues to test for the production of virus particles lacking envelope proteins, with the speculation of an involvement of the membrane-spanning region of the envelope protein in incorporation into virus particles. We have found that mutation of the N-terminal polybasic region redirected virus assembly to the cytoplasm, and we show that tryptophan residues may also play a significant role in the intracellular transport of the matrix protein. In total, 21 mutants of the Mo-MuLV matrix protein were produced, but we did not observe any mutant virus particles lacking the envelope glycoproteins, suggesting that a direct interaction between the Mo-MuLV matrix protein and envelope proteins either may not exist or may occur through multiple redundant interactions. PMID:9188629

  19. Mutagenesis analysis of the murine leukemia virus matrix protein: identification of regions important for membrane localization and intracellular transport.

    OpenAIRE

    Soneoka, Y; Kingsman, S M; Kingsman, A J

    1997-01-01

    We have created two sets of substitution mutations in the Moloney murine leukemia virus (Mo-MuLV) matrix protein in order to identify domains involved in association with the plasma membrane and in incorporation of the viral envelope glycoproteins into virus particles. The first set of mutations was targeted at putative membrane-associating regions similar to those of the human immunodeficiency virus type 1 matrix protein, which include a polybasic region at the N terminus of the Mo-MuLV matr...

  20. Projected Zika Virus Importation and Subsequent Ongoing Transmission after Travel to the 2016 Olympic and Paralympic Games - Country-Specific Assessment, July 2016.

    Science.gov (United States)

    Grills, Ardath; Morrison, Stephanie; Nelson, Bradley; Miniota, Jennifer; Watts, Alexander; Cetron, Martin S

    2016-07-22

    Zika virus belongs to the genus Flavivirus of the family Flaviviridae; it is transmitted to humans primarily through the bite of an infected Aedes species mosquito (e.g., Ae. aegypti and Ae. albopictus) (1). Zika virus has been identified as a cause of congenital microcephaly and other serious brain defects (2). As of June 30, 2016, CDC had issued travel notices for 49 countries and U.S. territories across much of the Western hemisphere (3), including Brazil, where the 2016 Olympic and Paralympic Games (Games of the XXXI Olympiad, also known as Rio 2016; Games) will be hosted in Rio de Janeiro in August and September 2016. During the Games, mosquito-borne Zika virus transmission is expected to be low because August and September are winter months in Brazil, when cooler and drier weather typically reduces mosquito populations (4). CDC conducted a risk assessment to predict those countries susceptible to ongoing Zika virus transmission resulting from introduction by a single traveler to the Games. Whereas all countries are at risk for travel-associated importation of Zika virus, CDC estimated that 19 countries currently not reporting Zika outbreaks have the environmental conditions and population susceptibility to sustain mosquito-borne transmission of Zika virus if a case were imported from infection at the Games. For 15 of these 19 countries, travel to Rio de Janeiro during the Games is not estimated to increase substantially the level of risk above that incurred by the usual aviation travel baseline for these countries. The remaining four countries, Chad, Djibouti, Eritrea, and Yemen, are unique in that they do not have a substantial number of travelers to any country with local Zika virus transmission, except for anticipated travel to the Games. These four countries will be represented by a projected, combined total of 19 athletes (plus a projected delegation of about 60 persons), a tiny fraction of the 350,000-500,000 visitors expected at the Games.* Overall