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Sample records for adapted influenza virus

  1. Host adaptation and transmission of influenza A viruses in mammals

    E.J.A. Schrauwen (Eefje); R.A.M. Fouchier (Ron)

    2014-01-01

    textabstractA wide range of influenza A viruses of pigs and birds have infected humans in the last decade, sometimes with severe clinical consequences. Each of these so-called zoonotic infections provides an opportunity for virus adaptation to the new host. Fortunately, most of these human infection

  2. Fitness seascapes and adaptive evolution of the influenza virus

    Lassig, Michael

    2014-03-01

    The seasonal human influenza A virus undergoes rapid genome evolution. This process is triggered by interactions with the host immune system and produces significant year-to-year sequence turnover in the population of circulating viral strains. We develop a dynamical fitness model that predicts the evolution of the viral population from one year to the next. Two factors are shown to determine the fitness of a viral strain: adaptive changes, which are under positive selection, and deleterious mutations, which affect conserved viral functions such as protein stability. Combined with the influenza strain tree, this fitness model maps the adaptive history of influenza A. We discuss the implications of our results for the statistical theory of adaptive evolution in asexual populations. Based on this and related systems, we touch upon the fundamental question of when evolution can be predicted. Joint work with Marta Luksza, Columbia University.

  3. Filamentous influenza viruses

    Dadonaite, Bernadeta; Vijyakrishnan, Swetha; Fodor, Ervin; Bhella, David; Hutchinson, Edward C.

    2016-01-01

    Clinical isolates of influenza virus produce pleomorphic virus particles, including extremely long filamentous virions. In contrast, strains of influenza that have adapted to laboratory growth typically produce only spherical virions. As a result, the filamentous phenotype has been overlooked in most influenza virus research. Recent advances in imaging and improved animal models have highlighted the distinct structure and functional relevance of filamentous virions. In this review we summaris...

  4. Cold-Adapted Pandemic 2009 H1N1 Influenza Virus Live Vaccine Elicits Cross-Reactive Immune Responses against Seasonal and H5 Influenza A Viruses

    Jang, Yo Han; Byun, Young Ho; Lee, Yoon Jae; Lee, Yun Ha; Lee, Kwang-Hee; Seong, Baik Lin

    2012-01-01

    The rapid transmission of the pandemic 2009 H1N1 influenza virus (pH1N1) among humans has raised the concern of a potential emergence of reassortment between pH1N1 and highly pathogenic influenza strains, especially the avian H5N1 influenza virus. Here, we report that the cold-adapted pH1N1 live attenuated vaccine (CApH1N1) elicits cross-reactive immunity to seasonal and H5 influenza A viruses in the mouse model. Immunization with CApH1N1 induced both systemic and mucosal antibodies with broa...

  5. Impact of host cell line adaptation on quasispecies composition and glycosylation of influenza A virus hemagglutinin.

    Jana Verena Roedig

    Full Text Available The genome of influenza A viruses is constantly changing (genetic drift resulting in small, gradual changes in viral proteins. Alterations within antibody recognition sites of the viral membrane glycoproteins hemagglutinin (HA and neuraminidase (NA result in an antigenetic drift, which requires the seasonal update of human influenza virus vaccines. Generally, virus adaptation is necessary to obtain sufficiently high virus yields in cell culture-derived vaccine manufacturing. In this study detailed HA N-glycosylation pattern analysis was combined with in-depth pyrosequencing analysis of the virus genomic RNA. Forward and backward adaptation from Madin-Darby Canine Kidney (MDCK cells to African green monkey kidney (Vero cells was investigated for two closely related influenza A virus PR/8/34 (H1N1 strains: from the National Institute for Biological Standards and Control (NIBSC or the Robert Koch Institute (RKI. Furthermore, stability of HA N-glycosylation patterns over ten consecutive passages and different harvest time points is demonstrated. Adaptation to Vero cells finally allowed efficient influenza A virus replication in Vero cells. In contrast, during back-adaptation the virus replicated well from the very beginning. HA N-glycosylation patterns were cell line dependent and stabilized fast within one (NIBSC-derived virus or two (RKI-derived virus successive passages during adaptation processes. However, during adaptation new virus variants were detected. These variants carried "rescue" mutations on the genomic level within the HA stem region, which result in amino acid substitutions. These substitutions finally allowed sufficient virus replication in the new host system. According to adaptation pressure the composition of the virus populations varied. In Vero cells a selection for "rescue" variants was characteristic. After back-adaptation to MDCK cells some variants persisted at indifferent frequencies, others slowly diminished and even

  6. Environmental connections of novel avian-origin H7N9 influenza virus infection and virus adaptation to the human.

    Li, Jun; Yu, Xinfen; Pu, Xiaoying; Xie, Li; Sun, Yongxiang; Xiao, Haixia; Wang, Fenjuan; Din, Hua; Wu, Ying; Liu, Di; Zhao, Guoqiu; Liu, Jun; Pan, Jingcao

    2013-06-01

    A novel H7N9 influenza A virus has been discovered as the causative identity of the emerging acute respiratory infection cases in Shanghai, China. This virus has also been identified in cases of infection in the neighboring area Hangzhou City in Zhejiang Province. In this study, epidemiologic, clinical, and virological data from three patients in Hangzhou who were confirmed to be infected by the novel H7N9 influenza A virus were collected and analyzed. Human respiratory specimens and chicken feces from a contacted free market were tested for influenza virus by real-time reverse transcription PCR (RT-PCR) and sequencing. The clinical features of the three cases were similar featured with high fever and severe respiratory symptoms; however, only one of the patients died. A certain degree of diversity was observed among the three Hangzhou viruses sequenced from human samples compared with other reported H7N9 influenza A viruses. The sequences of the novel avian-origin H7N9 influenza viruses from Hangzhou City contained important amino acid substitutions related to human adaptation. One of the Hangzhou viruses had gained a novel amino acid substitution (Q226I) in the receptor binding region of hemagglutinin. More importantly, the virus sequenced from the chicken feces had a 627E substitution in the PB2 protein instead of the mammalian-adapted 627K substitution that was found in the PB2 proteins from the Hangzhou viruses from the three patients. Therefore, the newly-emerging H7N9 virus might be under adaptation pressure that will help it "jump" from avian to human hosts. The significance of these substitutions needs further exploration, with both laboratory experiments and extensive field surveillance. PMID:23657795

  7. THE BIOLOGY OF INFLUENZA VIRUSES

    Bouvier, Nicole M.; Palese, Peter

    2008-01-01

    The influenza viruses are characterized by segmented, negative-strand RNA genomes requiring an RNA-dependent RNA polymerase of viral origin for replication. The particular structure of the influenza virus genome and function of its viral proteins enable antigenic drift and antigenic shift. These processes result in viruses able to evade the long-term adaptive immune responses in many hosts.

  8. Equine H7N7 influenza A viruses are highly pathogenic in mice without adaptation: potential use as an animal model.

    Kawaoka, Y.

    1991-01-01

    Equine H7N7 influenza A viruses, representing a broad range of isolates, were lethal in mice without adaptation. After repeated passages, A/Equine/London/1416/73 acquired neurotropism upon intranasal infection. Thus, mice infected with equine influenza A viruses provide a model system for the study of highly virulent mammalian influenza viruses.

  9. Evolution and adaptation of the pandemic A/H1N1 2009 influenza virus

    Ducatez MF

    2011-07-01

    Full Text Available Mariette F Ducatez, Thomas P Fabrizio, Richard J WebbyDepartment of Infectious Diseases, St Jude Children's Research Hospital, Memphis, TN, USAAbstract: The emergence of the 2009 H1N1 pandemic influenza virus [A(H1N1pdm09] has provided the public health community with many challenges, but also the scientific community with an opportunity to monitor closely its evolution through the processes of drift and shift. To date, and despite having circulated in humans for nearly two years, little antigenic variation has been observed in the A(H1N1pdm09 viruses. However, as the A(H1N1pdm09 virus continues to circulate and the immunologic pressure within the human population increases, future antigenic change is almost a certainty. Several coinfections of A(H1N1pdm09 and seasonal A(H1N1 or A(H3N2 viruses have been observed, but no reassortant viruses have been described in humans, suggesting a lack of fitness of reassortant viruses or a lack of opportunities for interaction of different viral lineages. In contrast, multiple reassortment events have been detected in swine populations between A(H1N1 pdm09 and other endemic swine viruses. Somewhat surprisingly, many of the well characterized influenza virus virulence markers appear to have limited impact on the phenotype of the A(H1N1pdm09 viruses when they have been introduced into mutant viruses in laboratory settings. As such, it is unclear what the evolutionary path of the pandemic virus will be, but the monitoring of any changes in the circulating viruses will remain a global public and animal health priority.Keywords: influenza, pandemic, evolution, adaptation

  10. Generation and characterization of a cold-adapted attenuated live H3N2 subtype influenza virus vaccine candidate

    AN Wen-qi; LIU Xiu-fan; WANG Xi-liang; YANG Peng-hui; DUAN Yue-qiang; LUO De-yan; TANG Chong; JIA Wei-hong; XING Li; SHI Xin-fu; ZHANG Yu-jing

    2009-01-01

    Background H3N2 subtype influenza A viruses have been identified in humans worldwide, raising concerns about their pandemic potential and prompting the development of candidate vaccines to protect humans against this subtype of influenza A virus. The aim of this study was to establish a system for rescuing of a cold-adapted high-yielding H3N2 subtype human influenza virus by reverse genetics. Methods In order to generate better and safer vaccine candidate viruses, a cold-adapted high yielding reassortant H3N2 influenza A virus was genetically constructed by reverse genetics and was designated as rgAA-H3N2. The rgAA-H3N2 virus contained HA and NA genes from an epidemic strain A/Wisconsin/67/2005 (H3N2) in a background of internal genes derived from the master donor viruses (MDV), cold-adapted (ca), temperature sensitive (te), live attenuated influenza virus strain A/Ann Arbor/6/60 (MDV-A). Results In this presentation, the virus HA titer of rgAA-H3N2 in the allantoic fluid from infected embryonated eggs was as high as 1:1024. A fluorescent focus assay (FFU) was performed 24-36 hours post-infection using a specific antibody and bright staining was used for determining the virus titer. The allantoic fluid containing the recovered influenza virus was analyzed in a hemagglutination inhibition (HI) test and the specific inhibition was found. Conclusion The results mentioned above demonstrated that cold-adapted, attenuated reassortant H3N2 subtype influenza A virus was successfully generated, which laid a good foundation for the further related research.

  11. Adaptation of high-growth influenza H5N1 vaccine virus in Vero cells: implications for pandemic preparedness.

    Tseng, Yu-Fen; Hu, Alan Yung-Chih; Huang, Mei-Liang; Yeh, Wei-Zhou; Weng, Tsai-Chuan; Chen, Yu-Shuan; Chong, Pele; Lee, Min-Shi

    2011-01-01

    Current egg-based influenza vaccine production technology can't promptly meet the global demand during an influenza pandemic as shown in the 2009 H1N1 pandemic. Moreover, its manufacturing capacity would be vulnerable during pandemics caused by highly pathogenic avian influenza viruses. Therefore, vaccine production using mammalian cell technology is becoming attractive. Current influenza H5N1 vaccine strain (NIBRG-14), a reassortant virus between A/Vietnam/1194/2004 (H5N1) virus and egg-adapted high-growth A/PR/8/1934 virus, could grow efficiently in eggs and MDCK cells but not Vero cells which is the most popular cell line for manufacturing human vaccines. After serial passages and plaque purifications of the NIBRG-14 vaccine virus in Vero cells, one high-growth virus strain (Vero-15) was generated and can grow over 10(8) TCID(50)/ml. In conclusion, one high-growth H5N1 vaccine virus was generated in Vero cells, which can be used to manufacture influenza H5N1 vaccines and prepare reassortant vaccine viruses for other influenza A subtypes. PMID:22022351

  12. Quantifying the fitness advantage of polymerase substitutions in Influenza A/H7N9 viruses during adaptation to humans.

    Judith M Fonville

    Full Text Available Adaptation of zoonotic influenza viruses towards efficient human-to-human transmissibility is a substantial public health concern. The recently emerged A/H7N9 influenza viruses in China provide an opportunity for quantitative studies of host-adaptation, as human-adaptive substitutions in the PB2 gene of the virus have been found in all sequenced human strains, while these substitutions have not been detected in any non-human A/H7N9 sequences. Given the currently available information, this observation suggests that the human-adaptive PB2 substitution might confer a fitness advantage to the virus in these human hosts that allows it to rise to proportions detectable by consensus sequencing over the course of a single human infection. We use a mathematical model of within-host virus evolution to estimate the fitness advantage required for a substitution to reach predominance in a single infection as a function of the duration of infection and the fraction of mutant present in the virus population that initially infects a human. The modeling results provide an estimate of the lower bound for the fitness advantage of this adaptive substitution in the currently sequenced A/H7N9 viruses. This framework can be more generally used to quantitatively estimate fitness advantages of adaptive substitutions based on the within-host prevalence of mutations. Such estimates are critical for models of cross-species transmission and host-adaptation of influenza virus infections.

  13. The Influenza Virus Enigma

    Salomon, Rachelle; Webster, Robert G.

    2009-01-01

    Both seasonal and pandemic influenza continue to challenge both scientists and clinicians. Drug-resistant H1N1 influenza viruses have dominated the 2009 flu season, and the H5N1 avian influenza virus continues to kill both people and poultry in Eurasia. Here, we discuss the pathogenesis and transmissibility of influenza viruses and we emphasize the need to find better predictors of both seasonal and potentially pandemic influenza.

  14. Genetic Adaptation of Influenza A Viruses in Domestic Animals and Their Potential Role in Interspecies Transmission: A Literature Review.

    Munoz, Olga; De Nardi, Marco; van der Meulen, Karen; van Reeth, Kristien; Koopmans, Marion; Harris, Kate; von Dobschuetz, Sophie; Freidl, Gudrun; Meijer, Adam; Breed, Andrew; Hill, Andrew; Kosmider, Rowena; Banks, Jill; Stärk, Katharina D C; Wieland, Barbara; Stevens, Kim; van der Werf, Sylvie; Enouf, Vincent; Dauphin, Gwenaelle; Dundon, William; Cattoli, Giovanni; Capua, Ilaria

    2016-03-01

    In December 2011, the European Food Safety Authority awarded a Grant for the implementation of the FLURISK project. The main objective of FLURISK was the development of an epidemiological and virological evidence-based influenza risk assessment framework (IRAF) to assess influenza A virus strains circulating in the animal population according to their potential to cross the species barrier and cause infections in humans. With the purpose of gathering virological data to include in the IRAF, a literature review was conducted and key findings are presented here. Several adaptive traits have been identified in influenza viruses infecting domestic animals and a significance of these adaptations for the emergence of zoonotic influenza, such as shift in receptor preference and mutations in the replication proteins, has been hypothesized. Nonetheless, and despite several decades of research, a comprehensive understanding of the conditions that facilitate interspecies transmission is still lacking. This has been hampered by the intrinsic difficulties of the subject and the complexity of correlating environmental, viral and host factors. Finding the most suitable and feasible way of investigating these factors in laboratory settings represents another challenge. The majority of the studies identified through this review focus on only a subset of species, subtypes and genes, such as influenza in avian species and avian influenza viruses adapting to humans, especially in the context of highly pathogenic avian influenza H5N1. Further research applying a holistic approach and investigating the broader influenza genetic spectrum is urgently needed in the field of genetic adaptation of influenza A viruses. PMID:25630935

  15. Synergistic Effect of S224P and N383D Substitutions in the PA of H5N1 Avian Influenza Virus Contributes to Mammalian Adaptation

    Song, Jiasheng; Xu, Jing; Shi, Jianzhong; Li, Yanbing; Chen, Hualan

    2015-01-01

    The adaptation of H5N1 avian influenza viruses to human poses a great threat to public health. Previous studies indicate the adaptive mutations in viral polymerase of avian influenza viruses are major contributors in overcoming the host species barrier, with the majority of mammalian adaptive mutations occurring in the PB2 protein. However, the adaptive mutations in the PA protein of the H5N1 avian influenza virus are less defined and poorly understood. In this study, we identified the synergistic effect of the PA/224P + 383D of H5N1 avian influenza viruses and its ability to enhance the pathogenicity and viral replication in a mammalian mouse model. Interestingly, the signature of PA/224P + 383D mainly exists in mammalian isolates of the H5N1 influenza virus and pdmH1N1 influenza virus, providing a potential pathway for the natural adaptation to mammals which imply the effects of natural adaptation to mammals. Notably, the mutation of PA/383D, which is highly conserved in avian influenza viruses, increases the polymerase activity in both avian and human cells, and may have roles in maintaining the avian influenza virus in their avian reservoirs, and jumping species to infect humans. PMID:26000865

  16. Synergistic Effect of S224P and N383D Substitutions in the PA of H5N1 Avian Influenza Virus Contributes to Mammalian Adaptation

    Jiasheng Song; Jing Xu; Jianzhong Shi; Yanbing Li; Hualan Chen

    2015-01-01

    The adaptation of H5N1 avian influenza viruses to human poses a great threat to public health. Previous studies indicate the adaptive mutations in viral polymerase of avian influenza viruses are major contributors in overcoming the host species barrier, with the majority of mammalian adaptive mutations occurring in the PB2 protein. However, the adaptive mutations in the PA protein of the H5N1 avian influenza virus are less defined and poorly understood. In this study, we identified the synerg...

  17. Multifunctional adaptive NS1 mutations are selected upon human influenza virus evolution in the mouse.

    Nicole E Forbes

    Full Text Available The role of the NS1 protein in modulating influenza A virulence and host range was assessed by adapting A/Hong Kong/1/1968 (H3N2 (HK-wt to increased virulence in the mouse. Sequencing the NS genome segment of mouse-adapted variants revealed 11 mutations in the NS1 gene and 4 in the overlapping NEP gene. Using the HK-wt virus and reverse genetics to incorporate mutant NS gene segments, we demonstrated that all NS1 mutations were adaptive and enhanced virus replication (up to 100 fold in mouse cells and/or lungs. All but one NS1 mutant was associated with increased virulence measured by survival and weight loss in the mouse. Ten of twelve NS1 mutants significantly enhanced IFN-β antagonism to reduce the level of IFN β production relative to HK-wt in infected mouse lungs at 1 day post infection, where 9 mutants induced viral yields in the lung that were equivalent to or significantly greater than HK-wt (up to 16 fold increase. Eight of 12 NS1 mutants had reduced or lost the ability to bind the 30 kDa cleavage and polyadenylation specificity factor (CPSF30 thus demonstrating a lack of correlation with reduced IFN β production. Mutant NS1 genes resulted in increased viral mRNA transcription (10 of 12 mutants, and protein production (6 of 12 mutants in mouse cells. Increased transcription activity was demonstrated in the influenza mini-genome assay for 7 of 11 NS1 mutants. Although we have shown gain-of-function properties for all mutant NS genes, the contribution of the NEP mutations to phenotypic changes remains to be assessed. This study demonstrates that NS1 is a multifunctional virulence factor subject to adaptive evolution.

  18. Taming influenza viruses

    Ozawa, Makoto; Kawaoka, Yoshihiro

    2011-01-01

    Plasmid-based reverse genetics systems allow the artificial generation of viruses with cloned cDNA-derived genomes. Since the establishment of such systems for influenza virus, numerous attempts have been made to tame this pathogenic agent. In particular, several types of viruses expressing foreign genes have been generated and used to further our knowledge of influenza virus replication and pathogenicity and to develop novel influenza vaccines. Here, we review these achievements and discuss ...

  19. Evolution of highly pathogenic avian influenza H5N1 viruses in Egypt indicating progressive adaptation.

    Arafa, A; Suarez, D; Kholosy, S G; Hassan, M K; Nasef, S; Selim, A; Dauphin, G; Kim, M; Yilma, J; Swayne, D; Aly, M M

    2012-10-01

    Highly pathogenic avian influenza (HPAI) virus of the H5N1 subtype was first diagnosed in poultry in Egypt in 2006, and since then the disease became enzootic in poultry throughout the country, affecting the poultry industry and village poultry as well as infecting humans. Vaccination has been used as a part of the control strategy to help to control the disease. Epidemiological data with sequence analysis of H5N1 viruses is important to link the mechanism of virus evolution in Egypt. This study describes the evolutionary pattern of Egyptian H5N1 viruses based on molecular characterization for the isolates collected from commercial poultry farms and village poultry from 2006 to 2011. Genetic analysis of the hemagglutinin (HA) gene was done by sequencing of the full-length H5 gene. The epidemiological pattern of disease outbreaks in Egyptian poultry farms seems to be seasonal with no specific geographic distribution across the country. The molecular epidemiological data revealed that there are two major groups of viruses: the classic group of subclade 2.2.1 and a variant group of 2.2.1.1. The classic group is prevailing mainly in village poultry and had fewer mutations compared to the originally introduced virus in 2006. Since 2009, this group has started to be transmitted back to commercial sectors. The variant group emerged by late 2007, was prevalent mainly in vaccinated commercial poultry, mutated continuously at a higher rate until 2010, and started to decline in 2011. Genetic analysis of the neuraminidase (NA) gene and the other six internal genes indicates a grouping of the Egyptian viruses similar to that obtained using the HA gene, with no obvious reassortments. The results of this study indicate that HPAI-H5N1 viruses are progressively evolving and adapting in Egypt and continue to acquire new mutations every season. PMID:22760662

  20. Swine Influenza/Variant Influenza Viruses

    ... Documents (General) Workers Employed at Commercial Swine Farms Influenza Types Seasonal Avian Swine Variant Pandemic Other Get ... this? Submit Button Past Newsletters Information on Swine Influenza/Variant Influenza Viruses Language: English Español Recommend ...

  1. Pandemic influenza A viruses escape from restriction by human MxA through adaptive mutations in the nucleoprotein.

    Benjamin Mänz

    2013-03-01

    Full Text Available The interferon-induced dynamin-like MxA GTPase restricts the replication of influenza A viruses. We identified adaptive mutations in the nucleoprotein (NP of pandemic strains A/Brevig Mission/1/1918 (1918 and A/Hamburg/4/2009 (pH1N1 that confer MxA resistance. These resistance-associated amino acids in NP differ between the two strains but form a similar discrete surface-exposed cluster in the body domain of NP, indicating that MxA resistance evolved independently. The 1918 cluster was conserved in all descendent strains of seasonal influenza viruses. Introduction of this cluster into the NP of the MxA-sensitive influenza virus A/Thailand/1(KAN-1/04 (H5N1 resulted in a gain of MxA resistance coupled with a decrease in viral replication fitness. Conversely, introduction of MxA-sensitive amino acids into pH1N1 NP enhanced viral growth in Mx-negative cells. We conclude that human MxA represents a barrier against zoonotic introduction of avian influenza viruses and that adaptive mutations in the viral NP should be carefully monitored.

  2. INFLUENZA VIRUS IN POULTRY

    Avian influenza virus (AIV) is normally found in wild birds, particularly in ducks and shorebirds, where it does not cause any perceptible clinical disease. However, poultry, including chickens and turkeys, are not normal hosts for avian influenza, but if the virus is introduced it can result in mi...

  3. Genetic Strategy to Prevent Influenza Virus Infections in Animals

    Chen, Jianzhu; Chen, Steve C.-Y.; Stern, Patrick; Scott, Benjamin B; Lois, Carlos

    2008-01-01

    The natural reservoirs of influenza viruses are aquatic birds. After adaptation, avian viruses can acquire the ability to infect humans and cause severe disease. Because domestic poultry serves as a key link between the natural reservoir of influenza viruses and epidemics and pandemics in human populations, an effective measure to control influenza would be to eliminate or reduce influenza virus infection in domestic poultry. The development and distribution of influenza-resistant poultry rep...

  4. Endocytosis of influenza viruses

    Lakadamyali, Melike; Rust, Michael J.; Zhuang, Xiaowei

    2004-01-01

    Receptor-mediated endocytosis is known to play an important role in the entry of many viruses into host cells. However, the exact internalization mechanism has, until recently, remained poorly understood for many medically important viruses, including influenza. Developments in real-time imaging of single viruses as well as the use of dominant negative mutants to selectively block specific endocytic pathways, have improved our understanding of the influenza infection process.

  5. Changes of morphological, biological and antigenic properties of avian influenza a virus hemagglutinin H2 in the course of adaptation to new host

    The alterations of avian influenza A virus hemagglutinin (HA) H2 as a result of adaptation to mice were first investigated in this study. HA of mouse-adapted (MA) variant was somewhat different from that of the original strain in electrophoretic mobility, antigenic structure and in hemagglutination activity with mouse red blood cells. (author)

  6. Amino acid substitutions occurring during adaptation of an emergent H5N6 avian influenza virus to mammals.

    Peng, Xiuming; Wu, Haibo; Peng, Xiaorong; Wu, Xiaoxin; Cheng, Linfang; Liu, Fumin; Ji, Shujing; Wu, Nanping

    2016-06-01

    Avian influenza viruses (AIVs) are known to cross species barriers, and emergent highly pathogenic H5N6 AIVs pose a serious threat to human health and the poultry industry. Here, we serially passaged an H5N6 virus 10 times in BALB/c mice. The pathogenicity of the wild-type 6D2 (WT-6D2) and mammal-adapted 6D2 strain (MA-6D2) were compared. The viral titer in multiple organs and the death rate for MA-6D2 were significantly higher than for WT-6D2. We provide evidence that the mutations HA A150V, NA R143K and G147E, PB2 E627K, and PA A343T may be important for adaptation of H5N6 AIVs to mammals. PMID:26997612

  7. Adaptation of High-Growth Influenza H5N1 Vaccine Virus in Vero Cells: Implications for Pandemic Preparedness

    Tseng, Yu-Fen; Hu, Alan Yung-Chih; Huang, Mei-Liang; Yeh, Wei-Zhou; Weng, Tsai-Chuan; Chen, Yu-Shuan; Chong, Pele; Lee, Min-Shi

    2011-01-01

    Current egg-based influenza vaccine production technology can't promptly meet the global demand during an influenza pandemic as shown in the 2009 H1N1 pandemic. Moreover, its manufacturing capacity would be vulnerable during pandemics caused by highly pathogenic avian influenza viruses. Therefore, vaccine production using mammalian cell technology is becoming attractive. Current influenza H5N1 vaccine strain (NIBRG-14), a reassortant virus between A/Vietnam/1194/2004 (H5N1) virus and egg-adap...

  8. Avian Influenza A Virus Infections in Humans

    ... Past Newsletters Avian Influenza A Virus Infections in Humans Language: English Español Recommend on Facebook Tweet ... A Viruses Avian Influenza A Virus Infections in Humans Although avian influenza A viruses usually do not ...

  9. Replication and transmission of influenza viruses in Japanese quail

    Quail have emerged as a potential intermediate host in the spread of avian influenza A viruses in poultry in Hong Kong. To better understand this possible role, we tested the replication and transmission in quail of influenza A viruses of all 15 HA subtypes. Quail supported the replication of at least 14 subtypes. Influenza A viruses replicated predominantly in the respiratory tract. Transmission experiments suggested that perpetuation of avian influenza viruses in quail requires adaptation. Swine influenza viruses were isolated from the respiratory tract of quail at low levels. There was no evidence of human influenza A or B virus replication. Interestingly, a human-avian recombinant containing the surface glycoprotein genes of a quail virus and the internal genes of a human virus replicated and transmitted readily in quail; therefore, quail could function as amplifiers of influenza virus reassortants that have the potential to infect humans and/or other mammalian species

  10. Serological evaluation of an influenza A virus cold-adapted reassortant live vaccine, CR-37 (H1N1), in Japanese adult volunteers.

    Yamane, N; Nakamura, Y.; Yuki, M.; Odagiri, T.; Ishida, N

    1984-01-01

    A cold-adapted influenza A virus, CR-37 (H1N1), derived from genetic reassortment between A/Ann Arbor/6/60 (H2N2) cold-adapted variant virus and A/California/10/78 (H1N1) wild-type virus, was tested in Japanese adult volunteer. The CR-37 live virus preparation induced only low-grade clinical reactions in volunteers for the first 3-4 days after inoculation. Two vaccinees who did not show any antibody changes became febrile (over 38.0 degrees C). Skin tests using the vaccine preparation and uni...

  11. Avian influenza viruses in humans.

    Malik Peiris, J S

    2009-01-01

    Past pandemics arose from low pathogenic avian influenza (LPAI) viruses. In more recent times, highly pathogenic avian influenza (HPAI) H5N1, LPAI H9N2 and both HPAI and LPAI H7 viruses have repeatedly caused zoonotic disease in humans. Such infections did not lead to sustained human-to-human transmission. Experimental infection of human volunteers and seroepidemiological studies suggest that avian influenza viruses of other subtypes may also infect humans. Viruses of the H7 subtype appear to...

  12. A live attenuated cold-adapted influenza A H7N3 virus vaccine provides protection against homologous and heterologous H7 viruses in mice and ferrets

    The appearance of human infections caused by avian influenza A H7 subtype viruses underscores their pandemic potential and the need to develop vaccines to protect humans from viruses of this subtype. A live attenuated H7N3 virus vaccine was generated by reverse genetics using the HA and NA genes of a low pathogenicity A/chicken/BC/CN-6/04 (H7N3) virus and the six internal protein genes of the cold-adapted A/Ann Arbor/6/60 ca (H2N2) virus. The reassortant H7N3 BC 04 ca vaccine virus was temperature sensitive and showed attenuation in mice and ferrets. Intranasal immunization with one dose of the vaccine protected mice and ferrets when challenged with homologous and heterologous H7 viruses. The reassortant H7N3 BC 04 ca vaccine virus showed comparable levels of attenuation, immunogenicity and efficacy in mice and ferret models. The safety, immunogenicity, and efficacy of this vaccine in mice and ferrets support the evaluation of this vaccine in clinical trials

  13. PB2-588 V promotes the mammalian adaptation of H10N8, H7N9 and H9N2 avian influenza viruses

    Xiao, Chencheng; Ma, Wenjun; Sun, Na; Huang, Lihong; Li, Yaling; Zeng, Zhaoyong; Wen, Yijun; Zhang, Zaoyue; Li, Huanan; Li, Qian; Yu, Yuandi; Zheng, Yi; Liu, Shukai; Hu, Pingsheng; Zhang, Xu; Ning, Zhangyong; Qi, Wenbao; Liao, Ming

    2016-01-01

    Human infections with avian influenza H7N9 or H10N8 viruses have been reported in China, raising concerns that they might cause human epidemics and pandemics. However, how these viruses adapt to mammalian hosts is unclear. Here we show that besides the commonly recognized viral polymerase subunit PB2 residue 627 K, other residues including 87E, 292 V, 340 K, 588 V, 648 V, and 676 M in PB2 also play critical roles in mammalian adaptation of the H10N8 virus. The avian-origin H10N8, H7N9, and H9N2 viruses harboring PB2-588 V exhibited higher polymerase activity, more efficient replication in mammalian and avian cells, and higher virulence in mice when compared to viruses with PB2-588 A. Analyses of available PB2 sequences showed that the proportion of avian H9N2 or human H7N9 influenza isolates bearing PB2-588 V has increased significantly since 2013. Taken together, our results suggest that the substitution PB2-A588V may be a new strategy for an avian influenza virus to adapt mammalian hosts. PMID:26782141

  14. Nucleocytoplasmic Shuttling of Influenza A Virus Proteins

    Jing Li

    2015-05-01

    Full Text Available Influenza viruses transcribe and replicate their genomes in the nuclei of infected host cells. The viral ribonucleoprotein (vRNP complex of influenza virus is the essential genetic unit of the virus. The viral proteins play important roles in multiple processes, including virus structural maintenance, mediating nucleocytoplasmic shuttling of the vRNP complex, virus particle assembly, and budding. Nucleocytoplasmic shuttling of viral proteins occurs throughout the entire virus life cycle. This review mainly focuses on matrix protein (M1, nucleoprotein (NP, nonstructural protein (NS1, and nuclear export protein (NEP, summarizing the mechanisms of their nucleocytoplasmic shuttling and the regulation of virus replication through their phosphorylation to further understand the regulation of nucleocytoplasmic shuttling in host adaptation of the viruses.

  15. The role of virus-specific human T cells in influenza A virus infection

    Guan, Jing; 管静

    2011-01-01

    Influenza A virus infection is a major cause of human morbidity and mortality. T cell immunity is believed to play critical roles for host defenses against influenza A infection. Once intracellular influenza A infection is established, viral clearance is mainly dependent on virus-specific CD8+ T cells. CD4+ T cells are important for adaptive immunity to natural influenza A infection or vaccination by providing help to B cells for antibody production and also providing help...

  16. Variant (Swine Origin) Influenza Viruses in Humans

    ... Past Newsletters Variant (Swine Origin) Influenza Viruses in Humans Language: English Español Recommend on Facebook Tweet ... Page Background Reporting Additional Information Key Facts about Human Infections with Variant Viruses (Swine Origin Influenza Viruses ...

  17. Intranasal Immunization with Influenza Virus-Like Particles Containing Membrane-Anchored Cholera Toxin B or Ricin Toxin B Enhances Adaptive Immune Responses and Protection against an Antigenically Distinct Virus

    Ji, Xianliang; Ren, Zhiguang; Xu, Na; Meng, Lingnan; Yu, Zhijun; Feng, Na; Sang, Xiaoyu; Li, Shengnan; Li, Yuanguo; Wang, Tiecheng; Zhao, Yongkun; Wang, Hualei; Zheng, Xuexing; Jin, Hongli; Li, Nan; Yang, Songtao; Cao, Jinshan; Liu, Wensen; Gao, Yuwei; Xia, Xianzhu

    2016-01-01

    Vaccination is the most effective means to prevent influenza virus infection, although current approaches are associated with suboptimal efficacy. Here, we generated virus-like particles (VLPs) composed of the hemagglutinin (HA), neuraminidase (NA) and matrix protein (M1) of A/Changchun/01/2009 (H1N1) with or without either membrane-anchored cholera toxin B (CTB) or ricin toxin B (RTB) as molecular adjuvants. The intranasal immunization of mice with VLPs containing membrane-anchored CTB or RTB elicited stronger humoral and cellular immune responses when compared to mice immunized with VLPs alone. Administration of VLPs containing CTB or RTB significantly enhanced virus-specific systemic and mucosal antibody responses, hemagglutination inhibiting antibody titers, virus neutralizing antibody titers, and the frequency of virus-specific IFN-γ and IL-4 secreting splenocytes. VLPs with and without CTB or RTB conferred complete protection against lethal challenge with a mouse-adapted homologous virus. When challenged with an antigenically distinct H1N1 virus, all mice immunized with VLPs containing CTB or RTB survived whereas mice immunized with VLPs alone showed only partial protection (80% survival). Our results suggest that membrane-anchored CTB and RTB possess strong adjuvant properties when incorporated into an intranasally-delivered influenza VLP vaccine. Chimeric influenza VLPs containing CTB or RTB may represent promising vaccine candidates for improved immunological protection against homologous and antigenically distinct influenza viruses. PMID:27110810

  18. Novel hemagglutinin-based influenza virus inhibitors

    Shen, Xintian; Zhang, Xuanxuan; Liu, Shuwen

    2013-01-01

    Influenza virus has caused seasonal epidemics and worldwide pandemics, which caused tremendous loss of human lives and socioeconomics. Nowadays, only two classes of anti-influenza drugs, M2 ion channel inhibitors and neuraminidase inhibitors respectively, are used for prophylaxis and treatment of influenza virus infection. Unfortunately, influenza virus strains resistant to one or all of those drugs emerge frequently. Hemagglutinin (HA), the glycoprotein in influenza virus envelope, plays a c...

  19. Genetic Reassortment Among the Influenza Viruses (Avian Influenza, Human Influenza and Swine Influenza) in Pigs

    Dyah Ayu Hewajuli; Ni Luh Putu Indi Dharmiayanti

    2012-01-01

    Influenza A virus is a hazardous virus and harm to respiratory tract. The virus infect birds, pigs, horses, dogs, mammals and humans. Pigs are important hosts in ecology of the influenza virus because they have two receptors, namely NeuAc 2,3Gal and NeuAc 2,6Gal which make the pigs are sensitive to infection of influenza virus from birds and humans and genetic reassortment can be occurred. Classical swine influenza H1N1 viruses had been circulated in pigs in North America and other countries ...

  20. Avian influenza virus RNA extraction

    The efficient extraction and purification of viral RNA is critical for down-stream molecular applications whether it is the sensitive and specific detection of virus in clinical samples, virus gene cloning and expression, or quantification of avian influenza (AI) virus by molecular methods from expe...

  1. Evidence of expanded host range and mammalian-associated genetic changes in a duck H9N2 influenza virus following adaptation in quail and chickens.

    Md Jaber Hossain

    Full Text Available H9N2 avian influenza viruses continue to circulate worldwide; in Asia, H9N2 viruses have caused disease outbreaks and established lineages in land-based poultry. Some H9N2 strains are considered potentially pandemic because they have infected humans causing mild respiratory disease. In addition, some of these H9N2 strains replicate efficiently in mice without prior adaptation suggesting that H9N2 strains are expanding their host range. In order to understand the molecular basis of the interspecies transmission of H9N2 viruses, we adapted in the laboratory a wildtype duck H9N2 virus, influenza A/duck/Hong Kong/702/79 (WT702 virus, in quail and chickens through serial lung passages. We carried out comparative analysis of the replication and transmission in quail and chickens of WT702 and the viruses obtained after 23 serial passages in quail (QA23 followed by 10 serial passages in chickens (QA23CkA10. Although the WT702 virus can replicate and transmit in quail, it replicates poorly and does not transmit in chickens. In contrast, the QA23CkA10 virus was very efficient at replicating and transmitting in quail and chickens. Nucleotide sequence analysis of the QA23 and QA23CkA10 viruses compared to the WT702 virus indicated several nucleotide substitutions resulting in amino acid changes within the surface and internal proteins. In addition, a 21-amino acid deletion was found in the stalk of the NA protein of the QA23 virus and was maintained without further modification in the QA23CkA10 adapted virus. More importantly, both the QA23 and the QA23CkA10 viruses, unlike the WT702 virus, were able to readily infect mice, produce a large-plaque phenotype, showed faster replication kinetics in tissue culture, and resulted in the quick selection of the K627 amino acid mammalian-associated signature in PB2. These results are in agreement with the notion that adaptation of H9 viruses to land-based birds can lead to strains with expanded host range.

  2. PB2-588 V promotes the mammalian adaptation of H10N8, H7N9 and H9N2 avian influenza viruses

    Chencheng Xiao; Wenjun Ma; Na Sun; Lihong Huang; Yaling Li; Zhaoyong Zeng; Yijun Wen; Zaoyue Zhang; Huanan Li; Qian Li; Yuandi Yu; Yi Zheng; Shukai Liu; Pingsheng Hu; Xu Zhang

    2016-01-01

    Human infections with avian influenza H7N9 or H10N8 viruses have been reported in China, raising concerns that they might cause human epidemics and pandemics. However, how these viruses adapt to mammalian hosts is unclear. Here we show that besides the commonly recognized viral polymerase subunit PB2 residue 627 K, other residues including 87E, 292 V, 340 K, 588 V, 648 V, and 676 M in PB2 also play critical roles in mammalian adaptation of the H10N8 virus. The avian-origin H10N8, H7N9, and H9...

  3. TMPRSS2 Independency for Haemagglutinin Cleavage In Vivo Differentiates Influenza B Virus from Influenza A Virus.

    Sakai, Kouji; Ami, Yasushi; Nakajima, Noriko; Nakajima, Katsuhiro; Kitazawa, Minori; Anraku, Masaki; Takayama, Ikuyo; Sangsriratanakul, Natthanan; Komura, Miyuki; Sato, Yuko; Asanuma, Hideki; Takashita, Emi; Komase, Katsuhiro; Takehara, Kazuaki; Tashiro, Masato; Hasegawa, Hideki; Odagiri, Takato; Takeda, Makoto

    2016-01-01

    Influenza A and B viruses show clear differences in their host specificity and pandemic potential. Recent studies have revealed that the host protease TMPRSS2 plays an essential role for proteolytic activation of H1, H3, and H7 subtype strains of influenza A virus (IAV) in vivo. IAV possessing a monobasic cleavage site in the haemagglutinin (HA) protein replicates poorly in TMPRSS2 knockout mice owing to insufficient HA cleavage. In the present study, human isolates of influenza B virus (IBV) strains and a mouse-adapted IBV strain were analysed. The data showed that IBV successfully underwent HA cleavage in TMPRSS2 knockout mice, and that the mouse-adapted strain was fully pathogenic to these mice. The present data demonstrate a clear difference between IAV and IBV in their molecular mechanisms for spreading in vivo. PMID:27389476

  4. TMPRSS2 Independency for Haemagglutinin Cleavage In Vivo Differentiates Influenza B Virus from Influenza A Virus

    Sakai, Kouji; Ami, Yasushi; Nakajima, Noriko; Nakajima, Katsuhiro; Kitazawa, Minori; Anraku, Masaki; Takayama, Ikuyo; Sangsriratanakul, Natthanan; Komura, Miyuki; Sato, Yuko; Asanuma, Hideki; Takashita, Emi; Komase, Katsuhiro; Takehara, Kazuaki; Tashiro, Masato; Hasegawa, Hideki; Odagiri, Takato; Takeda, Makoto

    2016-01-01

    Influenza A and B viruses show clear differences in their host specificity and pandemic potential. Recent studies have revealed that the host protease TMPRSS2 plays an essential role for proteolytic activation of H1, H3, and H7 subtype strains of influenza A virus (IAV) in vivo. IAV possessing a monobasic cleavage site in the haemagglutinin (HA) protein replicates poorly in TMPRSS2 knockout mice owing to insufficient HA cleavage. In the present study, human isolates of influenza B virus (IBV) strains and a mouse-adapted IBV strain were analysed. The data showed that IBV successfully underwent HA cleavage in TMPRSS2 knockout mice, and that the mouse-adapted strain was fully pathogenic to these mice. The present data demonstrate a clear difference between IAV and IBV in their molecular mechanisms for spreading in vivo. PMID:27389476

  5. Influenza Type A Viruses and Subtypes

    ... Research Making a Candidate Vaccine Virus Related Links Influenza Types Seasonal Avian Swine Variant Pandemic Other Get ... this? Submit What's this? Submit Button Past Newsletters Influenza Type A Viruses Language: English Español Recommend ...

  6. The cold adapted and temperature sensitive influenza A/Ann Arbor/6/60 virus, the master donor virus for live attenuated influenza vaccines, has multiple defects in replication at the restrictive temperature

    We have previously determined that the temperature sensitive (ts) and attenuated (att) phenotypes of the cold adapted influenza A/Ann Arbor/6/60 strain (MDV-A), the master donor virus for the live attenuated influenza A vaccines (FluMist), are specified by the five amino acids in the PB1, PB2 and NP gene segments. To understand how these loci control the ts phenotype of MDV-A, replication of MDV-A at the non-permissive temperature (39 deg. C) was compared with recombinant wild-type A/Ann Arbor/6/60 (rWt). The mRNA and protein synthesis of MDV-A in the infected MDCK cells were not significantly reduced at 39 deg. C during a single-step replication, however, vRNA synthesis was reduced and the nuclear-cytoplasmic export of viral RNP (vRNP) was blocked. In addition, the virions released from MDV-A infected cells at 39 deg. C exhibited irregular morphology and had a greatly reduced amount of the M1 protein incorporated. The reduced M1 protein incorporation and vRNP export blockage correlated well with the virus ts phenotype because these defects could be partially alleviated by removing the three ts loci from the PB1 gene. The virions and vRNPs isolated from the MDV-A infected cells contained a higher level of heat shock protein 70 (Hsp70) than those of rWt, however, whether Hsp70 is involved in thermal inhibition of MDV-A replication remains to be determined. Our studies demonstrate that restrictive replication of MDV-A at the non-permissive temperature occurs in multiple steps of the virus replication cycle

  7. Low-pathogenic avian influenza viruses in wild house mice.

    Susan A Shriner

    Full Text Available BACKGROUND: Avian influenza viruses are known to productively infect a number of mammal species, several of which are commonly found on or near poultry and gamebird farms. While control of rodent species is often used to limit avian influenza virus transmission within and among outbreak sites, few studies have investigated the potential role of these species in outbreak dynamics. METHODOLOGY/PRINCIPAL FINDINGS: We trapped and sampled synanthropic mammals on a gamebird farm in Idaho, USA that had recently experienced a low pathogenic avian influenza outbreak. Six of six house mice (Mus musculus caught on the outbreak farm were presumptively positive for antibodies to type A influenza. Consequently, we experimentally infected groups of naïve wild-caught house mice with five different low pathogenic avian influenza viruses that included three viruses derived from wild birds and two viruses derived from chickens. Virus replication was efficient in house mice inoculated with viruses derived from wild birds and more moderate for chicken-derived viruses. Mean titers (EID(50 equivalents/mL across all lung samples from seven days of sampling (three mice/day ranged from 10(3.89 (H3N6 to 10(5.06 (H4N6 for the wild bird viruses and 10(2.08 (H6N2 to 10(2.85 (H4N8 for the chicken-derived viruses. Interestingly, multiple regression models indicated differential replication between sexes, with significantly (p<0.05 higher concentrations of avian influenza RNA found in females compared with males. CONCLUSIONS/SIGNIFICANCE: Avian influenza viruses replicated efficiently in wild-caught house mice without adaptation, indicating mice may be a risk pathway for movement of avian influenza viruses on poultry and gamebird farms. Differential virus replication between males and females warrants further investigation to determine the generality of this result in avian influenza disease dynamics.

  8. Avian influenza virus in pregnancy.

    Liu, Shelan; Sha, Jianping; Yu, Zhao; Hu, Yan; Chan, Ta-Chien; Wang, Xiaoxiao; Pan, Hao; Cheng, Wei; Mao, Shenghua; Zhang, Run Ju; Chen, Enfu

    2016-07-01

    The unprecedented epizootic of avian influenza viruses, such as H5N1, H5N6, H7N1 and H10N8, has continued to cause disease in humans in recent years. In 2013, another novel influenza A (H7N9) virus emerged in China, and 30% of those patients died. Pregnant women are particularly susceptible to avian influenza and are more likely to develop severe complications and to die, especially when infection occurs in the middle and late trimesters. Viremia is believed to occur infrequently, and thus vertical transmission induced by avian influenza appears to be rare. However, avian influenza increases the risk of adverse pregnancy outcomes, including spontaneous abortion, preterm birth and fatal distress. This review summarises 39 cases of pregnant women and their fetuses from different countries dating back to 1997, including 11, 15 and 13 infections with H7N9, H5N1 and the 2009 pandemic influenza (H1N1), respectively. We analysed the epidemic features, following the geographical, population and pregnancy trimester distributions; underlying diseases; exposure history; medical timelines; human-to-human transmission; pathogenicity and vertical transmission; antivirus treatments; maternal severity and mortality and pregnancy outcome. The common experiences reported in different countries and areas suggest that early identification and treatment are imperative. In the future, vigilant virologic and epidemiologic surveillance systems should be developed to monitor avian influenza viruses during pregnancy. Furthermore, extensive study on the immune mechanisms should be conducted, as this will guide safe, rational immunomodulatory treatment among this high-risk population. Most importantly, we should develop a universal avian influenza virus vaccine to prevent outbreaks of the different subtypes. Copyright © 2016 John Wiley & Sons, Ltd. PMID:27187752

  9. Detection of influenza C virus but not influenza D virus in Scottish respiratory samples

    Smith, Donald B.; Gaunt, Eleanor R.; Digard, Paul; Templeton, Kate; Simmonds, Peter

    2016-01-01

    Highlights • “Influenza D” virus was not detected in Scottish respiratory samples (n = 3000). • Influenza C virus infection was present in 0.2% of respiratory samples. • Six influenza C virus complete genomes were sequenced. • Influenza C isolates comprised multiple, reassortant lineages.

  10. Molecular characterization of Indonesia avian influenza virus

    N.L.P.I. Dharmayanti

    2005-06-01

    Full Text Available Avian influenza outbreaks in poultry have been reported in Java island since August 2003. A total of 14 isolates of avian influenza virus has been isolated from October 2003 to October 2004. The viruses have been identified as HPAI H5N1 subtype. All of them were characterized further at genetic level and also for their pathogenicity. Phylogenetic analysis showed all of the avian influenza virus isolates were closely related to avian influenza virus from China (A/Duck/China/E319-2/03(H5N1. Molecular basis of pathogenicity in HA cleavage site indicated that the isolates of avian influenza virus have multiple basic amino acid (B-X-B-R indicating that all of the isolates representing virulent avian influenza virus (highly pathogenic avian influenza virus.

  11. H5N6 influenza virus infection, the newest influenza

    Beuy Joob

    2015-06-01

    Full Text Available The most recent new emerging infection is the H5N6 influenza virus infection. This infection has just been reported from China in early May 2014. The disease is believed to be a cross species infection. All indexed cases are from China. Of interest, the H5N6 influenza virus is the primary virus for avian. The avian H5N6 influenza virus in avian population is a low virulent strain. However, the clinical manifestation in human seems severe. In this mini-review, the authors summarize and discuss on this new emerging influenza.

  12. Identification of adaptive mutations in the influenza A virus non-structural 1 gene that increase cytoplasmic localization and differentially regulate host gene expression.

    Nicole Forbes

    Full Text Available The NS1 protein of influenza A virus (IAV is a multifunctional virulence factor. We have previously characterized gain-of-function mutations in the NS1 protein arising from the experimental adaptation of the human isolate A/Hong Kong/1/1968(H3N2 (HK to the mouse. The majority of these mouse adapted NS1 mutations were demonstrated to increase virulence, viral fitness, and interferon antagonism, but differ in binding to the post-transcriptional processing factor cleavage and polyadenylation specificity factor 30 (CPSF30. Because nuclear trafficking is a major genetic determinant of influenza virus host adaptation, we assessed subcellular localization and host gene expression of NS1 adaptive mutations. Recombinant HK viruses with adaptive mutations in the NS1 gene were assessed for NS1 protein subcellular localization in mouse and human cells using confocal microscopy and cellular fractionation. In human cells the HK wild-type (HK-wt virus NS1 protein partitioned equivalently between the cytoplasm and nucleus but was defective in cytoplasmic localization in mouse cells. Several adaptive mutations increased the proportion of NS1 in the cytoplasm of mouse cells with the greatest effects for mutations M106I and D125G. The host gene expression profile of the adaptive mutants was determined by microarray analysis of infected mouse cells to show either high or low extents of host-gene regulation (HGR or LGR phenotypes. While host genes were predominantly down regulated for the HGR group of mutants (D2N, V23A, F103L, M106I+L98S, L98S, M106V, and M106V+M124I, the LGR phenotype mutants (D125G, M106I, V180A, V226I, and R227K were characterized by a predominant up regulation of host genes. CPSF30 binding affinity of NS1 mutants did not predict effects on host gene expression. To our knowledge this is the first report of roles of adaptive NS1 mutations that impact intracellular localization and regulation of host gene expression.

  13. Comparison of vaccines for induction of heterosubtypic immunity to influenza A virus: cold-adapted vaccine versus DNA prime-adenovirus boost strategies.

    Lo, Chia-Yun; Wu, Zhengqi; Misplon, Julia A; Price, Graeme E; Pappas, Claudia; Kong, Wing-Pui; Tumpey, Terrence M; Epstein, Suzanne L

    2008-04-16

    Influenza epidemics or pandemics can arise for which strain- or subtype-matched vaccines are unavailable. Heterosubtypic immunity (Het-I) targeting conserved influenza A antigens could reduce morbidity and mortality during preparation of matched vaccines. Various vaccines inducing Het-I in animals have been studied separately using different viruses and conditions, but effectiveness for inducing Het-I has not been directly compared. The present studies compared immunization with cold-adapted (ca) viruses to DNA prime-recombinant adenovirus (rAd) boost vaccination to conserved antigens nucleoprotein (NP), matrix-2 (M2), or A/NP+M2. Both ca and DNA-rAd vaccinations induced antibody and T cell responses, and protected against lethal H1N1 challenge. Only A/NP+M2 DNA-rAd protected against challenge with highly pathogenic A/Vietnam/1203/2004 (H5N1); ca vaccine did not. Existing ca vaccines may provide some Het-I, but experimental vaccination focusing on conserved antigens was more effective in this model for protection against a divergent, highly pathogenic virus. PMID:18378366

  14. Adjuvant effects of invariant NKT cell ligand potentiates the innate and adaptive immunity to an inactivated H1N1 swine influenza virus vaccine in pigs.

    Dwivedi, Varun; Manickam, Cordelia; Dhakal, Santosh; Binjawadagi, Basavaraj; Ouyang, Kang; Hiremath, Jagadish; Khatri, Mahesh; Hague, Jacquelyn Gervay; Lee, Chang Won; Renukaradhya, Gourapura J

    2016-04-15

    Pigs are considered as the source of some of the emerging human flu viruses. Inactivated swine influenza virus (SwIV) vaccine has been in use in the US swine herds, but it failed to control the flu outbreaks. The main reason has been attributed to lack of induction of strong local mucosal immunity in the respiratory tract. Invariant natural killer T (iNKT) cell is a unique T cell subset, and activation of iNKT cell using its ligand α-Galactosylceramide (α-GalCer) has been shown to potentiate the cross-protective immunity to inactivated influenza virus vaccine candidates in mice. Recently, we discovered iNKT cell in pig and demonstrated its activation using α-GalCer. In this study, we evaluated the efficacy of an inactivated H1N1 SwIV coadministered with α-GalCer intranasally against a homologous viral challenge. Our results demonstrated the potent adjuvant effects of α-GalCer in potentiating both innate and adaptive immune responses to SwIV Ags in the lungs of pigs, which resulted in reduction in the lung viral load by 3 logs compared to without adjuvant. Immunologically, in the lungs of pigs vaccinated with α-GalCer an increased virus specific IgA response, IFN-α secretion and NK cell-cytotoxicity was observed. In addition, iNKT cell-stimulation enhanced the secretion of Th1 cytokines (IFN-γ and IL-12) and reduced the production of immunosuppressive cytokines (IL-10 and TGF-β) in the lungs of pigs⋅ In conclusion, we demonstrated for the first time iNKT cell adjuvant effects in pigs to SwIV Ags through augmenting the innate and adaptive immune responses in the respiratory tract. PMID:27016770

  15. Avian influenza A viruses: From zoonosis to pandemic

    M. Richard (Mathilde); M.T. de Graaf (Marieke); S. Herfst (Sander)

    2014-01-01

    textabstractZoonotic influenza A viruses originating from the animal reservoir pose a threat for humans, as they have the ability to trigger pandemics upon adaptation to and invasion of an immunologically naive population. Of particular concern are the H5N1 viruses that continue to circulate in poul

  16. H5N6 influenza virus infection, the newest influenza

    Beuy Joob; Wiwanitkit Viroj

    2015-01-01

    The most recent new emerging infection is the H5N6 influenza virus infection. This infection has just been reported from China in early May 2014. The disease is believed to be a cross species infection. All indexed cases are from China. Of interest, the H5N6 influenza virus is the primary virus for avian. The avian H5N6 influenza virus in avian population is a low virulent strain. However, the clinical manifestation in human seems severe. In this mini-review, the authors summarize and discuss...

  17. The Carbomer-Lecithin Adjuvant Adjuplex Has Potent Immunoactivating Properties and Elicits Protective Adaptive Immunity against Influenza Virus Challenge in Mice

    Wegmann, Frank; Moghaddam, Amin E.; Schiffner, Torben; Gartlan, Kate H.; Powell, Timothy J.; Russell, Rebecca A.; Baart, Matthijs; Carrow, Emily W.

    2015-01-01

    The continued discovery and development of adjuvants for vaccine formulation are important to safely increase potency and/or reduce the antigen doses of existing vaccines and tailor the adaptive immune response to newly developed vaccines. Adjuplex is a novel adjuvant platform based on a purified lecithin and carbomer homopolymer. Here, we analyzed the adjuvant activity of Adjuplex in mice for the soluble hemagglutinin (HA) glycoprotein of influenza A virus. The titration of Adjuplex revealed an optimal dose of 1% for immunogenicity, eliciting high titers of HA-specific IgG but inducing no significant weight loss. At this dose, Adjuplex completely protected mice from an otherwise lethal influenza virus challenge and was at least as effective as the adjuvants monophosphoryl lipid A (MPL) and alum in preventing disease. Adjuplex elicited balanced Th1-/Th2-type immune responses with accompanying cytokines and triggered antigen-specific CD8+ T-cell proliferation. The use of the peritoneal inflammation model revealed that Adjuplex recruited dendritic cells (DCs), monocytes, and neutrophils in the context of innate cytokine and chemokine secretion. Adjuplex neither triggered classical maturation of DCs nor activated a pathogen recognition receptor (PRR)-expressing NF-κB reporter cell line, suggesting a mechanism of action different from that reported for classical pathogen-associated molecular pattern (PAMP)-activated innate immunity. Taken together, these data reveal Adjuplex to be a potent and well-tolerated adjuvant with application for subunit vaccines. PMID:26135973

  18. Role of receptor binding specificity in influenza A virus transmission and pathogenesis

    De Graaf, M.; Fouchier, R. A. M.

    2014-01-01

    The recent emergence of a novel avian A/H7N9 influenza virus in poultry and humans in China, as well as laboratory studies on adaptation and transmission of avian A/H5N1 influenza viruses, has shed new light on influenza virus adaptation to mammals. One of the biological traits required for animal influenza viruses to cross the species barrier that received considerable attention in animal model studies, in vitro assays, and structural analyses is receptor binding specificity. Sialylated glyc...

  19. Evolution and ecology of influenza A viruses.

    Webster, R G; Bean, W J; Gorman, O T; Chambers, T M; Kawaoka, Y.

    1992-01-01

    In this review we examine the hypothesis that aquatic birds are the primordial source of all influenza viruses in other species and study the ecological features that permit the perpetuation of influenza viruses in aquatic avian species. Phylogenetic analysis of the nucleotide sequence of influenza A virus RNA segments coding for the spike proteins (HA, NA, and M2) and the internal proteins (PB2, PB1, PA, NP, M, and NS) from a wide range of hosts, geographical regions, and influenza A virus s...

  20. Molecular characterization of Indonesia avian influenza virus

    N.L.P.I Dharmayanti; R Damayanti; R Indriani; A Wiyono; R.M.A Adjid

    2005-01-01

    Avian influenza outbreaks in poultry have been reported in Java island since August 2003. A total of 14 isolates of avian influenza virus has been isolated from October 2003 to October 2004. The viruses have been identified as HPAI H5N1 subtype. All of them were characterized further at genetic level and also for their pathogenicity. Phylogenetic analysis showed all of the avian influenza virus isolates were closely related to avian influenza virus from China (A/Duck/China/E319-2/03(H5N1). Mo...

  1. Molecular patterns of avian influenza A viruses

    KOU Zheng; LEI FuMin; WANG ShengYue; ZHOU YanHong; LI TianXian

    2008-01-01

    Avian influenza A viruses could get across the species barrier and be fatal to humans. Highly patho-genic avian influenza H5N1 virus was an example. The mechanism of interspecies transmission is not clear as yet. In this research, the protein sequences of 237 influenza A viruses with different subtypes were transformed into pseudo-signals. The energy features were extracted by the method of wavelet packet decomposition and used for virus classification by the method of hierarchical clustering. The clustering results showed that five patterns existed in avian influenza A viruses, which associated with the phenotype of interspecies transmission, and that avian viruses with patterns C and E could across species barrier and those with patterns A, B and D might not have the abilities. The results could be used to construct an early warning system to predict the transmissibility of avian influenza A viruses to humans.

  2. The influence of the multi-basic cleavage site of the H5 hemagglutinin on the attenuation, immunogenicity and efficacy of a live attenuated influenza A h5N1 cold-adapted vaccine virus

    A recombinant live attenuated influenza virus (LAIV) deltaH5N1 vaccine with a modified hemagglutinin (HA) and intact neuraminidase genes from A/Vietnam/1203/04 (H5N1) and the six remaining genome segments from A/Ann Arbor/6/60 (H2N2) cold-adapted (AA ca) virus was attenuated in chickens, mice and fe...

  3. Identification of Newly Emerging Influenza Viruses by Surface-Enhanced Raman Spectroscopy.

    Lim, Jae-young; Nam, Jung-soo; Yang, Se-eun; Shin, Hyunku; Jang, Yoon-ha; Bae, Gyu-Un; Kang, Taewook; Lim, Kwang-il; Choi, Yeonho

    2015-12-01

    In this work, we demonstrate in situ virus identification based on surface-enhanced Raman scattering (SERS). We hypothesized that newly emerging influenza viruses possess surface proteins and lipids that can generate distinctive Raman signals. To test this hypothesis, SERS signals were measured from the surface of a noninfluenza virus, two different influenza viruses, and a genetically shuffled influenza virus. To ensure the safety for experimenters we constructed nonreplicating pseudotyped viruses that display main influenza virus surface components. Pseudotype with influenza virus components produced enhanced Raman peaks, on gold nanoparticles, that are easily distinguishable from those of pseudotype with a noninfluenza virus component, vesicular stomatitis virus G protein (VSVG). Furthermore, virus with the surface components of a newly emerging influenza strain, A/California/04/2009 (H1N1), generated Raman peaks different from those of viruses with components of the conventional laboratory-adapted influenza strain, A/WSN/33 (H1N1). Interestingly, the virus simultaneously displaying surface components of both influenza strains, a model mutant with genome reassortment, also produced a Raman signal pattern that is clearly distinguishable from those of each strain. This work highlights that SERS can provide a powerful label-free strategy to quickly identify newly emerging and potentially fatal influenza viruses. PMID:26528878

  4. Migratory birds and influenza virus

    Hubálek, Zdeněk

    Brno : ÚBO AV ČR, 2006 - (Procházka, P.; Sedláček, J.). s. 22-24 ISBN 80-903329-5-1. [Workshop of the Southeastern European Bird Migration Network (SEEN) /8./. 02.02.2006-05.02.2006, Praha] Institutional research plan: CEZ:AV0Z60930519 Keywords : migratory birds * influenza virus Subject RIV: EG - Zoology

  5. Characterization and evaluation of monoclonal antibodies developed for typing influenza A and influenza B viruses.

    Walls, H H; Harmon, M W; Slagle, J J; Stocksdale, C; Kendal, A P

    1986-01-01

    Monoclonal antibodies that are broadly reactive with influenza A or influenza B viruses were produced as stable reagents for typing influenza viruses. Monoclonal antibodies to influenza A were specific for either matrix protein or nucleoprotein. The antibodies to influenza B were specific for nucleoprotein or hemagglutinin protein. In an enzyme immunoassay procedure, influenza A antibodies detected H1N1, H2N2, and H3N2 influenza A virus strains collected between 1934 and 1984. Each of the inf...

  6. Immunity to seasonal and pandemic influenza A viruses

    Valkenburg, Sophie A.; Rutigliano, John A.; Ellebedy, Ali H.; Doherty, Peter C.; THOMAS, PAUL G.; Kedzierska, Katherine

    2011-01-01

    The introduction of a new influenza strain into human circulation leads to rapid global spread. This review summarizes innate and adaptive immunity to influenza viruses, with an emphasis on T-cell responses that provide cross-protection between distinct subtypes and strains. We discuss antigenic variation within T-cell immunogenic peptides and our understanding of pre-existing immunity towards the pandemic A(H1N1) 2009 strain.

  7. Immunology of avian influenza virus: a review.

    Suarez, D L; Schultz-Cherry, S

    2000-01-01

    Avian influenza virus can cause serious disease in a wide variety of birds and mammals, but its natural host range is in wild ducks, gulls, and shorebirds. Infections in poultry can be inapparent or cause respiratory disease, decreases in production, or a rapidly fatal systemic disease known as highly pathogenic avian influenza (HPAI). For the protection of poultry, neutralizing antibody to the hemagglutinin and neuraminidase proteins provide the primary protection against disease. A variety of vaccines elicit neutralizing antibody, including killed whole virus vaccines and fowl-pox recombinant vaccines. Antigenic drift of influenza viruses appears to be less important in causing vaccine failures in poultry as compared to humans. The cytotoxic T lymphocyte response can reduce viral shedding in mildly pathogenic avian influenza viruses, but provides questionable protection against HPAI. Influenza viruses can directly affect the immune response of infected birds, and the role of the Mx gene, interferons, and other cytokines in protection from disease remains unknown. PMID:10717293

  8. Emerging influenza virus: A global threat

    M Khanna; P Kumar; K Choudhary; B Kumar; V K Vijayan

    2008-11-01

    Since 1918, influenza virus has been one of the major causes of morbidity and mortality, especially among young children. Though the commonly circulating strain of the virus is not virulent enough to cause mortality, the ability of the virus genome to mutate at a very high rate may lead to the emergence of a highly virulent strain that may become the cause of the next pandemic. Apart from the influenza virus strain circulating in humans (H1N1 and H3N2), the avian influenza H5N1 H7 and H9 virus strains have also been reported to have caused human infections, H5N1 H7 and H9 have shown their ability to cross the species barrier from birds to humans and further replicate in humans. This review addresses the biological and epidemiological aspects of influenza virus and efforts to have a control on the virus globally.

  9. Cellular Proteins in Influenza Virus Particles

    Shaw, Megan L.; Stone, Kathryn L.; Colangelo, Christopher M.; Gulcicek, Erol E.; Peter Palese

    2008-01-01

    Virions are thought to contain all the essential proteins that govern virus egress from the host cell and initiation of replication in the target cell. It has been known for some time that influenza virions contain nine viral proteins; however, analyses of other enveloped viruses have revealed that proteins from the host cell can also be detected in virions. To address whether the same is true for influenza virus, we used two complementary mass spectrometry approaches to perform a comprehensi...

  10. Improving the representativeness of influenza viruses shared within the WHO Global Influenza Surveillance and Response System

    Pereyaslov, Dmitriy; Zemtsova, Galina; Gruessner, Christine; Daniels, Rodney S.; McCauley, John W.; Brown, Caroline S

    2016-01-01

    Background Sharing influenza viruses within the WHO Global Influenza Surveillance and Response System is crucial for monitoring evolution of influenza viruses. Objectives Analysis of timeliness and geographic representativeness of viruses shared by National Influenza Centres (NICs) in the WHO European Region with the London WHO Collaborating Centre for Reference and Research on Influenza for the Northern Hemisphere's 2010–2011 and 2011–2012 influenza seasons. Materials and methods Data from N...

  11. Cellular proteins in influenza virus particles.

    Megan L Shaw

    2008-06-01

    Full Text Available Virions are thought to contain all the essential proteins that govern virus egress from the host cell and initiation of replication in the target cell. It has been known for some time that influenza virions contain nine viral proteins; however, analyses of other enveloped viruses have revealed that proteins from the host cell can also be detected in virions. To address whether the same is true for influenza virus, we used two complementary mass spectrometry approaches to perform a comprehensive proteomic analysis of purified influenza virus particles. In addition to the aforementioned nine virus-encoded proteins, we detected the presence of 36 host-encoded proteins. These include both cytoplasmic and membrane-bound proteins that can be grouped into several functional categories, such as cytoskeletal proteins, annexins, glycolytic enzymes, and tetraspanins. Interestingly, a significant number of these have also been reported to be present in virions of other virus families. Protease treatment of virions combined with immunoblot analysis was used to verify the presence of the cellular protein and also to determine whether it is located in the core of the influenza virus particle. Immunogold labeling confirmed the presence of membrane-bound host proteins on the influenza virus envelope. The identification of cellular constituents of influenza virions has important implications for understanding the interactions of influenza virus with its host and brings us a step closer to defining the cellular requirements for influenza virus replication. While not all of the host proteins are necessarily incorporated specifically, those that are and are found to have an essential role represent novel targets for antiviral drugs and for attenuation of viruses for vaccine purposes.

  12. Biopolymer encapsulated live influenza virus as a universal CD8+ T cell vaccine against influenza virus

    Boesteanu, Alina C.; Babu, Nadarajan S.; Wheatley, Margaret; Papazoglou, Elisabeth S.; Katsikis, Peter D.

    2010-01-01

    Current influenza virus vaccines primarily elicit antibodies and can be rendered ineffective by antigenic drift and shift. Vaccines that elicit CD8+ T cell responses targeting less variable proteins may function as universal vaccines that have broad reactivity against different influenza virus strains. To generate such a universal vaccine, we encapsulated live influenza virus in a biopolymer and delivered it to mice subcutaneously. This vaccine was safe, induced potent CD8+ T cell immunity an...

  13. Genetic characterization of an adapted pandemic 2009 H1N1 influenza virus that reveals improved replication rates in human lung epithelial cells.

    Wörmann, Xenia; Lesch, Markus; Welke, Robert-William; Okonechnikov, Konstantin; Abdurishid, Mirshat; Sieben, Christian; Geissner, Andreas; Brinkmann, Volker; Kastner, Markus; Karner, Andreas; Zhu, Rong; Hinterdorfer, Peter; Anish, Chakkumkal; Seeberger, Peter H; Herrmann, Andreas; Meyer, Thomas F; Karlas, Alexander

    2016-05-01

    The 2009 influenza pandemic originated from a swine-origin H1N1 virus, which, although less pathogenic than anticipated, may acquire additional virulence-associated mutations in the future. To estimate the potential risk, we sequentially passaged the isolate A/Hamburg/04/2009 in A549 human lung epithelial cells. After passage 6, we observed a 100-fold increased replication rate. High-throughput sequencing of viral gene segments identified five dominant mutations, whose contribution to the enhanced growth was analyzed by reverse genetics. The increased replication rate was pinpointed to two mutations within the hemagglutinin (HA) gene segment (HA1 D130E, HA2 I91L), near the receptor binding site and the stem domain. The adapted virus also replicated more efficiently in mice in vivo. Enhanced replication rate correlated with increased fusion pH of the HA protein and a decrease in receptor affinity. Our data might be relevant for surveillance of pre-pandemic strains and development of high titer cell culture strains for vaccine production. PMID:26914510

  14. Epidemic Status of Swine Influenza Virus in China

    Kong, Weili; Ye, Jiahui; Guan, Shangsong; Liu, Jinhua; Pu, Juan

    2013-01-01

    As one of the most significant swine diseases, in recent years, swine influenza (SI) has had an immense impact on public health and has raised extensive public concerns in China. Swine are predisposed to both avian and human influenza virus infections, between that and/or swine influenza viruses, genetic reassortment could occur. This analysis aims at introducing the history of swine influenza virus, the serological epidemiology of swine influenza virus infection, the clinical details of swin...

  15. A brief introduction to avian influenza virus

    Avian influenza virus (AIV) causes a disease of high economic importance for poultry production worldwide. The earliest recorded cases of probable high pathogenicity AIV in poultry were reported in Italy in the 1870’s and avian influenza been recognized in domestic poultry through the modern era of ...

  16. Characterization of an H10N8 influenza virus isolated from Dongting lake wetland

    Chen Jianjun

    2011-01-01

    Full Text Available Abstract Background Wild birds, especially those in wetlands and aquatic environments, are considered to be natural reservoirs of avian influenza viruses. It is accepted that water is an important component in the transmission cycle of avian influenza virus. Monitoring the water at aggregation and breeding sites of migratory waterfowl, mainly wetland, is very important for early detection of avian influenza virus. The epidemiology investigation of avian influenza virus was performed in Dongting lake wetland which is an international important wetland. Results An H10N8 influenza virus was isolated from Dongting Lake wetland in 2007. Phylogenetic analysis indicated that the virus was generated by multiple gene segment reassortment. The isolate was lowly pathogenic for chickens. However, it replicated efficiently in the mouse lung without prior adaptation, and the virulence to mice increased rapidly during adaptation in mouse lung. Sequence analysis of the genome of viruses from different passages showed that multiple amino acid changes were involved in the adaptation of the isolates to mice. Conclusions The water might be an important component in the transmission cycle of avian influenza virus, and other subtypes of avian influenza viruses (other than H5, H7 and H9 might evolve to pose a potential threat to mammals and even humans.

  17. Biochemical Impact of the Host Adaptation-associated PB2 E627K Mutation on the Temperature-dependent RNA Synthesis Kinetics of Influenza A Virus Polymerase Complex*

    Aggarwal, Shilpa; Dewhurst, Stephen; Takimoto, Toru; Kim, Baek

    2011-01-01

    Most avian influenza A viruses, which preferentially replicate at the high temperatures found in the digestive tract of birds, have a glutamic acid at residue 627 of the viral RNA polymerase PB2 subunit (Glu-627), whereas the human viruses, which optimally replicate at the low temperatures observed in the human respiratory tract, have a lysine (Lys-627). The mechanism of action for this mutation is still not understood, although interaction with host factors has been proposed to play a major ...

  18. H5N1 influenza viruses: outbreaks and biological properties

    Neumann, Gabriele; Chen, Hualan; Gao, George F.; Shu, Yuelong; Kawaoka, Yoshihiro

    2009-01-01

    All known subtypes of influenza A viruses are maintained in wild waterfowl, the natural reservoir of these viruses. Influenza A viruses are isolated from a variety of animal species with varying morbidity and mortality rates. More importantly, influenza A viruses cause respiratory disease in humans with potentially fatal outcome. Local or global outbreaks in humans are typically characterized by excess hospitalizations and deaths. In 1997, highly pathogenic avian influenza viruses of the H5N1...

  19. Avian Influenza Virus: The Threat of A Pandemic

    Shih-Cheng Chang; Yi-Ying Cheng; Shin-Ru Shih

    2006-01-01

    The 1918 influenza A virus pandemic caused a death toll of 40~50 million. Currently,because of the widespread dissemination of the avian influenza virus (H5N1), there is a highrisk of another pandemic. Avian species are the natural hosts for numerous subtypes ofinfluenza A viruses; however, the highly pathogenic avian influenza virus (HPAI) is not onlyextremely lethal to domestic avian species but also can infect humans and cause death. Thisreview discusses why the avian influenza virus is co...

  20. Avian Influenza A H7N9 Virus Induces Severe Pneumonia in Mice without Prior Adaptation and Responds to a Combination of Zanamivir and COX-2 Inhibitor

    Li, Can; Li, Chuangen; Anna J X Zhang; To, Kelvin K. W.; Andrew C Y Lee; Zhu, Houshun; Wu, Hazel W. L.; Chan, Jasper F. W.; Chen, Honglin; Hung, Ivan F. N.; Li, Lanjuan; Yuen, Kwok-Yung

    2014-01-01

    Background Human infection caused by the avian influenza A H7N9 virus has a case-fatality rate of over 30%. Systematic study of the pathogenesis of avian H7N9 isolate and effective therapeutic strategies are needed. Methods BALB/c mice were inoculated intranasally with an H7N9 virus isolated from a chicken in a wet market epidemiologically linked to a fatal human case, (A/chicken/Zhejiang/DTID-ZJU01/2013 [CK1]), and with an H7N9 virus isolated from a human (A/Anhui/01/2013 [AH1]). The pulmona...

  1. Recent zoonoses caused by influenza A viruses.

    Alexander, D J; Brown, I H

    2000-04-01

    Influenza is a highly contagious, acute illness which has afflicted humans and animals since ancient times. Influenza viruses are part of the Orthomyxoviridae family and are grouped into types A, B and C according to antigenic characteristics of the core proteins. Influenza A viruses infect a large variety of animal species, including humans, pigs, horses, sea mammals and birds, occasionally producing devastating pandemics in humans, such as in 1918, when over twenty million deaths occurred world-wide. The two surface glycoproteins of the virus, haemagglutinin (HA) and neuraminidase (NA), are the most important antigens for inducing protective immunity in the host and therefore show the greatest variation. For influenza A viruses, fifteen antigenically distinct HA subtypes and nine NA subtypes are recognised at present; a virus possesses one HA and one NA subtype, apparently in any combination. Although viruses of relatively few subtype combinations have been isolated from mammalian species, all subtypes, in most combinations, have been isolated from birds. In the 20th Century, the sudden emergence of antigenically different strains in humans, termed antigenic shift, has occurred on four occasions, as follows, in 1918 (H1N1), 1957 (H2N2), 1968 (H3N2) and 1977 (H1N1), each resulting in a pandemic. Frequent epidemics have occurred between the pandemics as a result of gradual antigenic change in the prevalent virus, termed antigenic drift. Currently, epidemics occur throughout the world in the human population due to infection with influenza A viruses of subtypes H1N1 and H3N2 or with influenza B virus. The impact of these epidemics is most effectively measured by monitoring excess mortality due to pneumonia and influenza. Phylogenetic studies suggest that aquatic birds could be the source of all influenza A viruses in other species. Human pandemic strains are thought to have emerged through one of the following three mechanisms: genetic reassortment (occurring as a

  2. Avian Influenza A (H7N9) Virus

    ... Research Making a Candidate Vaccine Virus Related Links Influenza Types Seasonal Avian Swine Variant Pandemic Other Get ... Submit What's this? Submit Button Past Newsletters Avian Influenza A (H7N9) Virus Language: English Español Recommend ...

  3. Transmission of Avian Influenza A Viruses Between Animals and People

    ... Newsletters Transmission of Avian Influenza A Viruses Between Animals and People Language: English Español Recommend on ... Compartir Influenza A viruses have infected many different animals, including ducks, chickens, pigs, whales, horses, and seals. ...

  4. M2e-displaying virus-like particles with associated RNA promote T helper 1 type adaptive immunity against influenza A.

    Lorena Itatí Ibañez

    Full Text Available The ectodomain of influenza A matrix protein 2 (M2e is a candidate for a universal influenza A vaccine. We used recombinant Hepatitis B core antigen to produce virus-like particles presenting M2e (M2e-VLPs. We produced the VLPs with and without entrapped nucleic acids and compared their immunogenicity and protective efficacy. Immunization of BALB/c mice with M2e-VLPs containing nucleic acids induced a stronger, Th1-biased antibody response compared to particles lacking nucleic acids. The former also induced a stronger M2e-specific CD4(+ T cell response, as determined by ELISPOT. Mice vaccinated with alum-adjuvanted M2e-VLPs containing the nucleic acid-binding domain were better protected against influenza A virus challenge than mice vaccinated with similar particles lacking this domain, as deduced from the loss in body weight following challenge with X47 (H3N2 or PR/8 virus. Challenge of mice that had been immunized with M2e-VLPs with or without nucleic acids displayed significantly lower mortality, morbidity and lung virus titers than control-immunized groups. We conclude that nucleic acids present in M2e-VLPs correlate with improved immune protection.

  5. Avian influenza A viruses: from zoonosis to pandemic

    Richard, Mathilde; de Graaf, Miranda; Herfst, Sander

    2014-01-01

    Zoonotic influenza A viruses originating from the animal reservoir pose a threat for humans, as they have the ability to trigger pandemics upon adaptation to and invasion of an immunologically naive population. Of particular concern are the H5N1 viruses that continue to circulate in poultry in numerous countries in Europe, Asia and Africa, and the recently emerged H7N9 viruses in China, due to their relatively high number of human fatalities and pandemic potential. To start a pandemic, zoonot...

  6. The pathogenesis of H3N8 canine influenza virus in chickens and turkeys

    Canine influenza virus (CIV) of the H3N8 subtype has emerged in dog populations throughout the U.S. where it has become endemic in kennels and animal shelters in some regions of the U.S. CIV is believed to be an equine influenza that was transmitted to and adapted to dogs. It has not previously bee...

  7. Guinea pig model for evaluating the potential public health risk of swine and avian influenza viruses.

    Yipeng Sun

    Full Text Available BACKGROUND: The influenza viruses circulating in animals sporadically transmit to humans and pose pandemic threats. Animal models to evaluate the potential public health risk potential of these viruses are needed. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the guinea pig as a mammalian model for the study of the replication and transmission characteristics of selected swine H1N1, H1N2, H3N2 and avian H9N2 influenza viruses, compared to those of pandemic (H1N1 2009 and seasonal human H1N1, H3N2 influenza viruses. The swine and avian influenza viruses investigated were restricted to the respiratory system of guinea pigs and shed at high titers in nasal tracts without prior adaptation, similar to human strains. None of the swine and avian influenza viruses showed transmissibility among guinea pigs; in contrast, pandemic (H1N1 2009 virus transmitted from infected guinea pigs to all animals and seasonal human influenza viruses could also horizontally transmit in guinea pigs. The analysis of the receptor distribution in the guinea pig respiratory tissues by lectin histochemistry indicated that both SAα2,3-Gal and SAα2,6-Gal receptors widely presented in the nasal tract and the trachea, while SAα2,3-Gal receptor was the main receptor in the lung. CONCLUSIONS/SIGNIFICANCE: We propose that the guinea pig could serve as a useful mammalian model to evaluate the potential public health threat of swine and avian influenza viruses.

  8. Is low pathogenic avian influenza virus virulent for wild waterbirds?

    Kuiken, T

    2013-01-01

    Although low pathogenic avian influenza virus (LPAIV) is traditionally considered to have adapted to its wild waterbird host to become avirulent, recent studies have suggested that LPAIV infection might after all have clinical effects. Therefore, I reviewed the literature on LPAIV infections in wild waterbirds. The virulence of LPAIV was assessed in 17 studies on experimental infections and nine studies on natural infections. Reported evidence for virulence were reductions in return rate, fee...

  9. Influenza

    Ferroni, Eliana; Jefferson, Tom

    2011-01-01

    Influenza viruses are constantly altering their antigenic structure, and every year the WHO recommends which strains of influenza should be included in vaccines. During the autumn–winter months, influenza circulates more frequently (influenza seasons), causing a greater proportion of influenza-like illness and sometimes serious seasonal epidemics.The incidence of symptoms depends on the underlying immunity of the population.

  10. Influenza

    Jefferson, Tom

    2009-01-01

    Influenza viruses are constantly altering their antigenic structure, and every year the WHO recommends which strains of influenza should be included in vaccines. During the autumn-winter months, influenza circulates more frequently (influenza seasons), causing a greater proportion of influenza-like illness, and sometimes serious seasonal epidemics.The incidence of infection depends on the underlying immunity of the population.

  11. Nasal commensal Staphylococcus epidermidis counteracts influenza virus

    Chen, Hui-Wen; Liu, Pei-Feng; Liu, Yu-Tsueng; Kuo, Sherwin; Zhang, Xing-Quan; Schooley, Robert T.; Rohde, Holger; Gallo, Richard L.; Huang, Chun-Ming

    2016-01-01

    Several microbes, including Staphylococcus epidermidis (S. epidermidis), a Gram-positive bacterium, live inside the human nasal cavity as commensals. The role of these nasal commensals in host innate immunity is largely unknown, although bacterial interference in the nasal microbiome may promote ecological competition between commensal bacteria and pathogenic species. We demonstrate here that S. epidermidis culture supernatants significantly suppressed the infectivity of various influenza viruses. Using high-performance liquid chromatography together with mass spectrometry, we identified a giant extracellular matrix-binding protein (Embp) as the major component involved in the anti-influenza effect of S. epidermidis. This anti-influenza activity was abrogated when Embp was mutated, confirming that Embp is essential for S. epidermidis activity against viral infection. We also showed that both S. epidermidis bacterial particles and Embp can directly bind to influenza virus. Furthermore, the injection of a recombinant Embp fragment containing a fibronectin-binding domain into embryonated eggs increased the survival rate of virus-infected chicken embryos. For an in vivo challenge study, prior Embp intranasal inoculation in chickens suppressed the viral titres and induced the expression of antiviral cytokines in the nasal tissues. These results suggest that S. epidermidis in the nasal cavity may serve as a defence mechanism against influenza virus infection. PMID:27306590

  12. Composting for Avian Influenza Virus Elimination

    Elving, Josefine; Emmoth, Eva; Albihn, Ann; Vinnerås, Björn; Ottoson, Jakob

    2012-01-01

    Effective sanitization is important in viral epizootic outbreaks to avoid further spread of the pathogen. This study examined thermal inactivation as a sanitizing treatment for manure inoculated with highly pathogenic avian influenza virus H7N1 and bacteriophages MS2 and ϕ6. Rapid inactivation of highly pathogenic avian influenza virus H7N1 was achieved at both mesophilic (35°C) and thermophilic (45 and 55°C) temperatures. Similar inactivation rates were observed for bacteriophage ϕ6, while b...

  13. Effect of receptor binding domain mutations on receptor binding and transmissibility of avian influenza H5N1 viruses

    Maines, Taronna R; Chen, Li-Mei; Van Hoeven, Neal; Tumpey, Terrence M; Blixt, Ola; Belser, Jessica A; Gustin, Kortney M; Pearce, Melissa B; Pappas, Claudia; Stevens, James; Cox, Nancy J; Paulson, James C; Raman, Rahul; Sasisekharan, Ram; Katz, Jacqueline M; Donis, Ruben O

    2011-01-01

    Although H5N1 influenza viruses have been responsible for hundreds of human infections, these avian influenza viruses have not fully adapted to the human host. The lack of sustained transmission in humans may be due, in part, to their avian-like receptor preference. Here, we have introduced...

  14. Avian influenza viruses - new causative a gents of human infections

    Hrnjaković-Cvjetković Ivana; Cvjetković Dejan; Jerant-Patić Vera; Milošević Vesna; Tadić-Radovanov Jelena; Kovačević Gordana

    2006-01-01

    Introduction. Influenza A viruses can infect humans, some mammals and especially birds. Subtypes of human influenza A viruses: ACH1N1), ACH2N2) and A(H3N2) have caused pandemics. Avian influenza viruses vary owing to their 15 hemagglutinins (H) and 9 neuraminidases (N). Human cases of avian influenza A In the Netherlands in 2003, there were 83 human cases of influenza A (H7N7). In 1997, 18 cases of H5N1 influenza A, of whom 6 died, were found among residents of Hong Kong. In 2004, 34 human ca...

  15. Radioimmunoassay of influenza A virus haemagglutinin. II

    Individual rabbits differed greatly in their antibody response to the ''strain-specific'' and ''cross-reactive'' antigenic determinants on the hemagglutinin (HA) subunit of influenza virus recombinant MRC11 (H3N2) and influenza virus Dunedin (H3N2), after immunization with whole virus or bromelain-released hemagglutinin (B-HA). Consequently, diverse cross-reactions between these viruses and A/Hong Kong/68 virus were found in the hemagglutination inhibition (HI) test as well as in homologous radioimmunoassay (125I-B-HA from MRC11: anti MRC11 serum, and 125I-B-HA from Dunedin: anti Dunedin serum) when sera from different animals were employed. Radioimmunoassay (RIA), over and above to the HI test, was also able to differentiate clearly the respective HAs with antisera reacting to the same HI titre with both corresponding influenza virus strains. Thus it appeared that antigenic differences could be identified with higher sensitivity by homologous RIA than by the HI test and that multiple antigenic determinants were reactive on the 125I-B-HA in the RIA procedure employed. MRC11 and A/HK/68 viruses were also compared by heterologous RIA (125I-B-HA from MRC11: anti A/HK/68 serum). It was found that preferentially antigenic determinants with a high degree of cross-reactivity could be studied in the heterologous system. (author)

  16. THE MOLECULAR BIOLOGY OF AVIAN INFLUENZA VIRUS IN SHORT

    Avian influenza virus (AIV) is an important pathogen of poultry as it can cause severe economic losses through disease, including respiratory signs and mortality, and effects on trade. Avian influenza virus is classified as type A influenza, which is a member of the orthomyxoviridae family. Charact...

  17. Symptoms of influenza virus infection in hospitalized patients

    van den Dool, C; Hak, E; Wallinga, J; van Loon, A M; Lammers, J W J; Bonten, M J M

    2008-01-01

    BACKGROUND: During influenza outbreaks, fever and cough are the most accurate symptoms in predicting influenza virus infection in the community. OBJECTIVE: To determine the usefulness of fever, cough, and other symptoms for diagnosing influenza virus infection in hospitalized patients. DESIGN: Prosp

  18. Interaction of nanodiamonds materials with influenza viruses

    The perspectives of the application of modern materials contained nanodiamonds (ND) are considered in this study. The interaction between detonation paniculate ND, soot and influenza A and B viruses, fragments of cDNA were analyzed at the normal conditions. It was shown that these sorbents can interact with the following viruses: reference epidemic strains of influenza A(H1N1), A(H1N1)v, A(H3N2) and B viruses circulated in the word in 2000-2010. The allantoises, concentrated viruses, cDNA can be absorbed by ND sorbents and getting removed from water solutions within 20 min. ND sorbents can be used for the preparation of antivirus filters for water solution and for future diagnostic systems in virology.

  19. Radioimmunoassay of influenza A virus haemagglutinin. I

    Haemagglutinin released from influenza A virus recombinant MRC11 [antigenically identical to the strain A/Port Chalmers/1/73 (H3N2)] by bromelain treatment and purified by rate zonal centrifugation (further on B-HA) was examined for possible contamination by neuraminidase. Specific enzymatic activities of the MRC11 virus and the B-HA respectively showed that B-HA contained less than 0.1% of enzymatically active neuraminidase originally present in the virus. Gel double diffusion tests, specificities of rabbit antisera induced by B-HA as well as radioimmunoprecipitation experiments demonstrated that B-HA was devoid of any antigenically active neuraminidase. Precipitation of 125I-labelled B-HA with antisera to influenza virus recombinants with N2 neuraminidase was evidently caused by antibodies to host antigenic determinant(s) present in these sera. As for purity and radioimmunoprecipitation properties, B-HA is quite suitable for radioimmunoassay experiments. (author)

  20. Protective effects of phillyrin against influenza A virus in vivo.

    Qu, Xin-Yan; Li, Qing-Jun; Zhang, Hui-Min; Zhang, Xiao-Juan; Shi, Peng-Hui; Zhang, Xiu-Juan; Yang, Jing; Zhou, Zhe; Wang, Sheng-Qi

    2016-07-01

    Influenza A virus infection represents a great threat to public health. However, owing to side effects and the emergence of resistant virus strains, the use of currently available anti-influenza drugs may be limited. In order to identify novel anti-influenza drugs, we investigated the antiviral effects of phillyrin against influenza A virus infection in vivo. The mean survival time, lung index, viral titers, influenza hemagglutinin (HA) protein and serum cytokines levels, and histopathological changes in lung tissue were examined. Administration of phillyrin at a dose of 20 mg/kg/day for 3 days significantly prolonged the mean survival time, reduced the lung index, decreased the virus titers and interleukin-6 levels, reduced the expression of HA, and attenuated lung tissue damage in mice infected with influenza A virus. Taken together, these data showed that phillyrin had potential protective effects against infection caused by influenza A virus. PMID:27323762

  1. Avian Influenza: Mixed Infections and Missing Viruses

    Wentworth, David E.; Dugan, Vivien G.; Xudong Lin; Seth Schobel; Magdalena Plancarte; Kelly, Terra R.; Lindsay, LeAnn L.; Boyce, Walter M.

    2013-01-01

    A high prevalence and diversity of avian influenza (AI) viruses were detected in a population of wild mallards sampled during summer 2011 in California, providing an opportunity to compare results obtained before and after virus culture. We tested cloacal swab samples prior to culture by matrix real-time PCR, and by amplifying and sequencing a 640bp portion of the hemagglutinin (HA) gene. Each sample was also inoculated into embryonated chicken eggs, and full genome sequences were determined ...

  2. Emergence of European Avian Influenza Virus-Like H1N1 Swine Influenza A Viruses in China▿

    Liu, Jinhua; Bi, Yuhai; Qin, Kun; Fu, Guanghua; Yang, Jun; Peng, Jinshan; Ma, Guangpeng; Liu, Qinfang; Pu, Juan; Tian, Fulin

    2009-01-01

    During swine influenza surveillance from 2007 to 2008, 10 H1N1 viruses were isolated and analyzed for their antigenic and phylogenetic properties. Our study revealed the emergence of avian-origin European H1N1 swine influenza virus in China, which highlights the necessity of swine influenza surveillance for potential pandemic preparedness.

  3. Spatiotemporal Analysis of the Genetic Diversity of Seal Influenza A(H10N7) Virus, Northwestern Europe

    Bodewes, Rogier; Zohari, Siamak; Krog, Jesper Schak;

    2016-01-01

    birds to seals, amino acid changes in HA may occur rapidly and are important for virus adaptation to its new mammalian host. Influenza A viruses are major pathogens for humans, domestic animals, and wildlife. In addition to the continuous circulation of influenza A viruses among various host species...... to various avian influenza A(H10N7) viruses. The collection of samples from infected seals during the course of the outbreak provided a unique opportunity to follow the adaptation of the avian virus to its new seal host. Sequence data for samples collected from 41 different seals from four different...... found in H10 viruses isolated from Eurasian birds. Also, sequence variation in the HA gene was greater at the beginning than at the end of the epidemic, when a number of the mutations observed earlier had been fixed. These results imply that when an avian influenza virus jumps the species barrier from...

  4. Animal Models for Influenza Viruses: Implications for Universal Vaccine Development

    Irina Margine; Florian Krammer

    2014-01-01

    Influenza virus infections are a significant cause of morbidity and mortality in the human population. Depending on the virulence of the influenza virus strain, as well as the immunological status of the infected individual, the severity of the respiratory disease may range from sub-clinical or mild symptoms to severe pneumonia that can sometimes lead to death. Vaccines remain the primary public health measure in reducing the influenza burden. Though the first influenza vaccine preparation wa...

  5. Current Approaches for Diagnosis of Influenza Virus Infections in Humans

    Vemula, Sai Vikram; Zhao, Jiangqin; Liu, Jikun; Wang, Xue; Biswas, Santanu; Hewlett, Indira

    2016-01-01

    Despite significant advancement in vaccine and virus research, influenza continues to be a major public health concern. Each year in the United States of America, influenza viruses are responsible for seasonal epidemics resulting in over 200,000 hospitalizations and 30,000–50,000 deaths. Accurate and early diagnosis of influenza viral infections are critical for rapid initiation of antiviral therapy to reduce influenza related morbidity and mortality both during seasonal epidemics and pandemi...

  6. Influenza virus types and subtypes among pediatric patients having influenza like illness in summer season

    Bishwanath Acharya; Bishnu Prasad Upadhyay; Shailaja Adhikari; Ajit Rayamajhi; Kanchan Thapa

    2016-01-01

    Background: Acute respiratory infections (ARIs) represent one of the major causes of childhood mortality and morbidity in Nepal. The Influenza virus is one of the common causes of viral ARIs and bacterial infection secondary to influenza contributes to majority of childhood death worldwide. However, the diagnosis of influenza virus infection is not routinely suggested in Nepal even for children clinically presenting with influenza like illness (ILI). Methods: With an aim to describe the statu...

  7. Localization of influenza virus proteins to nuclear dot 10 structures in influenza virus-infected cells

    We studied influenza virus M1 protein by generating HeLa and MDCK cell lines that express M1 genetically fused to green fluorescent protein (GFP). GFP-M1 was incorporated into virions produced by influenza virus infected MDCK cells expressing the fusion protein indicating that the fusion protein is at least partially functional. Following infection of either HeLa or MDCK cells with influenza A virus (but not influenza B virus), GFP-M1 redistributes from its cytosolic/nuclear location and accumulates in nuclear dots. Immunofluorescence revealed that the nuclear dots represent nuclear dot 10 (ND10) structures. The colocalization of authentic M1, as well as NS1 and NS2 protein, with ND10 was confirmed by immunofluorescence following in situ isolation of ND10. These findings demonstrate a previously unappreciated involvement of influenza virus with ND10, a structure involved in cellular responses to immune cytokines as well as the replication of a rapidly increasing list of viruses

  8. The pathogenesis of H3N8 canine influenza virus in chickens, turkeys and ducks

    Canine influenza virus (CIV) of the H3N8 subtype has emerged in dog populations throughout the U.S. where is has become endemic in kennels and animal shelters in some regions. It has not previously been determined whether the canine adapted virus can be transmitted to domestic poultry, which are su...

  9. El virus influenza y la gripe aviar

    Libia Herrero-Uribe

    2008-03-01

    Full Text Available En este artículo se presenta una revisión del virus influenza,su biología,sus mecanismos de variación antigénica,las pandemias que ha producido y la prevención mediante las vacunas y medicamentos antivirales.Se analizan las razones por las cuales aparece el virus H5N1 que produce la fiebre aviar en humanos,la patogénesis de este virus y las estrategias para su prevención.Se informa sobre el plan de preparación para la pandemia en los niveles nacional e internacional.

  10. Highly Pathogenic Avian Influenza Virus Infection in Feral Raccoons, Japan

    Horimoto, Taisuke; Maeda, Ken; Murakami, Shin; Kiso, Maki; Iwatsuki-Horimoto, Kiyoko; SASHIKA, Mariko; Ito, Toshihiro; Suzuki, Kazuo; Yokoyama, Mayumi; Kawaoka, Yoshihiro

    2011-01-01

    Although raccoons (Procyon lotor) are susceptible to influenza viruses, highly pathogenic avian influenza virus (H5N1) infection in these animals has not been reported. We performed a serosurvey of apparently healthy feral raccoons in Japan and found specific antibodies to subtype H5N1 viruses. Feral raccoons may pose a risk to farms and public health.

  11. Global migration of influenza A viruses in swine

    The emergence of the 2009 A/H1N1 pandemic virus underscores the importance of understanding how influenza A viruses evolve in swine on a global scale. To reveal the frequency, patterns and drivers of the spread of swine influenza virus globally, we conducted the largest phylogenetic analysis of swin...

  12. Improved and simplified recombineering approach for influenza virus reverse genetics

    Liu, Qinfang; Wang, Shuai; Ma, Guangpeng; Pu, Juan; Forbes, Nicole E.; Brown, Earl G.; Liu, Jin-Hua

    2009-01-01

    Typical reverse genetics systems for generating influenza viruses require the insertion of each genome segments by DNA ligation into vectors for genome synthesis and expression. Herein is described the construction and use of a novel pair of plasmid vectors for cloning all eight genome segments of influenza A virus by homologous recombination for influenza virus reverse genetics. Plasmids, pLLBA and pLLBG, were constructed to possess opposing RNA polymerase I and RNA polymerase II transcripti...

  13. Animal Models for Influenza Virus Pathogenesis and Transmission

    Lowen, Anice C.; Bouvier, Nicole M.

    2010-01-01

    Influenza virus infection of humans results in a respiratory disease that ranges in severity from sub-clinical infection to primary viral pneumonia that can result in death. The clinical effects of infection vary with the exposure history, age and immune status of the host, and also the virulence of the influenza strain. In humans, the virus is transmitted through either aerosol or contact-based transfer of infectious respiratory secretions. As is evidenced by most zoonotic influenza virus in...

  14. Avian influenza viruses - new causative a gents of human infections

    Hrnjaković-Cvjetković Ivana

    2006-01-01

    Full Text Available Introduction. Influenza A viruses can infect humans, some mammals and especially birds. Subtypes of human influenza A viruses: ACH1N1, ACH2N2 and A(H3N2 have caused pandemics. Avian influenza viruses vary owing to their 15 hemagglutinins (H and 9 neuraminidases (N. Human cases of avian influenza A In the Netherlands in 2003, there were 83 human cases of influenza A (H7N7. In 1997, 18 cases of H5N1 influenza A, of whom 6 died, were found among residents of Hong Kong. In 2004, 34 human cases (23 deaths were reported in Viet Nam and Thailand. H5N1 virus-infected patients presented with fever and respiratory symptoms. Complications included respiratory distress syndrome, renal failure, liver dysfunction and hematologic disorders. Since 1999, 7 cases of human influenza H9N2 infection have been identified in China and Hong Kong. The importance of human infection with avian influenza viruses. H5N1 virus can directly infect humans. Genetic reassortment of human and avian influenza viruses may occur in humans co infected with current human A(HIN1 or A(H3N2 subtypes and avian influenza viruses. The result would be a new influenza virus with pandemic potential. All genes of H5Nl viruses isolated from humans are of avian origin. Prevention and control. The reassortant virus containing H and N from avian and the remaining proteins from human influenza viruses will probably be used as a vaccine strain. The most important control measures are rapid destruction of all infected or exposed birds and rigorous disinfection of farms. Individuals exposed to suspected animals should receive prophylactic treatment with antivirals and annual vaccination. .

  15. Pathogenicity of highly pathogenic avian influenza virus in mammals

    de Wit, Emmie; Kawaoka, Yoshihiro; de Jong, Menno; Fouchier, Ron

    2008-01-01

    textabstractIn recent years, there has been an increase in outbreaks of highly pathogenic avian influenza (HPAI) in poultry. Occasionally, these outbreaks have resulted in transmission of influenza viruses to humans and other mammals, with symptoms ranging from conjunctivitis to pneumonia and death. Here, the current knowledge of the determinants of pathogenicity of HPAI viruses in mammals is summarized. It is becoming apparent that common mechanisms exist across influenza A virus strains and...

  16. The Regulation of Autophagy by Influenza A Virus

    Rong Zhang

    2014-01-01

    Full Text Available Influenza A virus is a dreadful pathogen of animals and humans, causing widespread infection and severe morbidity and mortality. It is essential to characterize the influenza A virus-host interaction and develop efficient counter measures against the viral infection. Autophagy is known as a catabolic process for the recycling of the cytoplasmic macromolecules. Recently, it has been shown that autophagy is a critical mechanism underlying the interaction between influenza A virus and its host. Autophagy can be induced by the infection with influenza A virus, which is considered as a necessary process for the viral proliferation, including the accumulation of viral elements during the replication of influenza A virus. On the other hand, influenza A virus can inhibit the autophagic formation via interaction with the autophagy-related genes (Atg and signaling pathways. In addition, autophagy is involved in the influenza virus-regulated cell deaths, leading to significant changes in host apoptosis. Interestingly, the high pathogenic strains of influenza A virus, such as H5N1, stimulate autophagic cell death and appear to interplay with the autophagy in distinct ways as compared with low pathogenic strains. This review discusses the regulation of autophagy, an influenza A virus driven process.

  17. Virulence of Avian Influenza A Viruses for Squirrel Monkeys

    Murphy, Brian R.; Hinshaw, Virginia S.; Sly, D. Lewis; London, William T.; Hosier, Nanette T.; Wood, Frank T.; Webster, Robert G.; Chanock, Robert M.

    1982-01-01

    Ten serologically distinct avian influenza A viruses were administered to squirrel monkeys and hamsters to compare their replication and virulence with those of human influenza A virus, A/Udorn/307/72 (H3N2). In squirrel monkeys, the 10 avian influenza A viruses exhibited a spectrum of replication and virulence. The levels of virus replication and clinical response were closely correlated. Two viruses, A/Mallard/NY/6874/78 (H3N2) and A/Pintail/Alb/121/79 (H7N8), resembled the human virus in t...

  18. The global antigenic diversity of swine influenza A viruses

    Lewis, Nicola S; Russell, Colin A; Langat, Pinky;

    2016-01-01

    Swine influenza presents a substantial disease burden for pig populations worldwide and poses a potential pandemic threat to humans. There is considerable diversity in both H1 and H3 influenza viruses circulating in swine due to the frequent introductions of viruses from humans and birds coupled...... with geographic segregation of global swine populations. Much of this diversity is characterized genetically but the antigenic diversity of these viruses is poorly understood. Critically, the antigenic diversity shapes the risk profile of swine influenza viruses in terms of their epizootic and pandemic...... potential. Here, using the most comprehensive set of swine influenza virus antigenic data compiled to date, we quantify the antigenic diversity of swine influenza viruses on a multi-continental scale. The substantial antigenic diversity of recently circulating viruses in different parts of the world adds...

  19. Influenza virus vaccine for neglected hosts: horses and dogs

    2016-01-01

    This study provides information regarding vaccine research and the epidemiology of influenza virus in neglected hosts (horses and dogs). Equine influenza virus (EIV) causes a highly contagious disease in horses and other equids, and outbreaks have occurred worldwide. EIV has resulted in costly damage to the horse industry and has the ability of cross the host species barrier from horses to dogs. Canine influenza is a virus of equine or avian origin and infects companion animals that live in close contact with humans; this results in possible exposure to the seasonal epizootic influenza virus. There have been case reports of genetic reassortment between human and canine influenza viruses, which results in high virulence and the ability of transmission to ferrets. This emphasizes the need for vaccine research on neglected hosts to update knowledge on current strains and to advance technology for controlling influenza outbreaks for public health. PMID:27489801

  20. Inhibition of influenza virus infection and hemagglutinin cleavage by the protease inhibitor HAI-2

    Highlights: • Biochemical and cell biological analysis of HAI-2 as an inhibitor of influenza HA cleavage activation. • Biochemical and cell biological analysis of HAI-2 as an inhibitor of influenza virus infection. • Comparative analysis of HAI-2 for vesicular stomatitis virus and human parainfluenza virus type-1. • Analysis of the activity of HAI-2 in a mouse model of influenza. - Abstract: Influenza virus remains a significant concern to public health, with the continued potential for a high fatality pandemic. Vaccination and antiviral therapeutics are effective measures to circumvent influenza virus infection, however, multiple strains have emerged that are resistant to the antiviral therapeutics currently on the market. With this considered, investigation of alternative antiviral therapeutics is being conducted. One such approach is to inhibit cleavage activation of the influenza virus hemagglutinin (HA), which is an essential step in the viral replication cycle that permits viral-endosome fusion. Therefore, targeting trypsin-like, host proteases responsible for HA cleavage in vivo may prove to be an effective therapeutic. Hepatocyte growth factor activator inhibitor 2 (HAI-2) is naturally expressed in the respiratory tract and is a potent inhibitor of trypsin-like serine proteases, some of which have been determined to cleave HA. In this study, we demonstrate that HAI-2 is an effective inhibitor of cleavage of HA from the human-adapted H1 and H3 subtypes. HAI-2 inhibited influenza virus H1N1 infection in cell culture, and HAI-2 administration showed protection in a mouse model of influenza. HAI-2 has the potential to be an effective, alternative antiviral therapeutic for influenza

  1. Inhibition of influenza virus infection and hemagglutinin cleavage by the protease inhibitor HAI-2

    Hamilton, Brian S.; Chung, Changik; Cyphers, Soreen Y.; Rinaldi, Vera D.; Marcano, Valerie C.; Whittaker, Gary R., E-mail: grw7@cornell.edu

    2014-07-25

    Highlights: • Biochemical and cell biological analysis of HAI-2 as an inhibitor of influenza HA cleavage activation. • Biochemical and cell biological analysis of HAI-2 as an inhibitor of influenza virus infection. • Comparative analysis of HAI-2 for vesicular stomatitis virus and human parainfluenza virus type-1. • Analysis of the activity of HAI-2 in a mouse model of influenza. - Abstract: Influenza virus remains a significant concern to public health, with the continued potential for a high fatality pandemic. Vaccination and antiviral therapeutics are effective measures to circumvent influenza virus infection, however, multiple strains have emerged that are resistant to the antiviral therapeutics currently on the market. With this considered, investigation of alternative antiviral therapeutics is being conducted. One such approach is to inhibit cleavage activation of the influenza virus hemagglutinin (HA), which is an essential step in the viral replication cycle that permits viral-endosome fusion. Therefore, targeting trypsin-like, host proteases responsible for HA cleavage in vivo may prove to be an effective therapeutic. Hepatocyte growth factor activator inhibitor 2 (HAI-2) is naturally expressed in the respiratory tract and is a potent inhibitor of trypsin-like serine proteases, some of which have been determined to cleave HA. In this study, we demonstrate that HAI-2 is an effective inhibitor of cleavage of HA from the human-adapted H1 and H3 subtypes. HAI-2 inhibited influenza virus H1N1 infection in cell culture, and HAI-2 administration showed protection in a mouse model of influenza. HAI-2 has the potential to be an effective, alternative antiviral therapeutic for influenza.

  2. The capillary electrophoresis of the influenza viruses

    Horká, Marie; Kubesová, Anna; Kubíček, O.; Kubíčková, Z.; Rosenbergová, K.; Šlais, Karel

    Tallinn: Tallinn University of Technology, 2009 - (Borissova, M.; Vaher, M.). s. 93 ISBN 978-9985-59-930-3. [Nordic Separation Science Society (NoSSS) International Conference /5./. 26.08.2009-29.08.2009, Tallinn] R&D Projects: GA AV ČR IAAX00310701 Institutional research plan: CEZ:AV0Z40310501 Keywords : capillary isoelectric focusing * capillary electrophoresis * influenza swine and equine viruses Subject RIV: CB - Analytical Chemistry, Separation

  3. Molecular diagnostics of Avian influenza virus

    Petrović Tamaš; Lazić Sava; Kapetanov Miloš; Velhner Maja

    2006-01-01

    The success of supervizing an infectious disease depends on the ability for speedy detection and characterization of the cause and the forming of a corresponding system for examining the success of control implemented in order to prevent a recurrence of the disease. Since influenza viruses continue to circle, causing significant morbidity and mortality both among the human population and among animals all over the world, it is essential to secure the timely identification and monitoring of th...

  4. Aerosolized avian influenza virus by laboratory manipulations

    Li Zhiping; Li Jinsong; Zhang Yandong; Li Lin; Ma Limin; Li Dan; Gao Feng; Xia Zhiping

    2012-01-01

    Abstract Background Avian H5N1 influenza viruses present a challenge in the laboratory environment, as they are difficult to collect from the air due to their small size and relatively low concentration. In an effort to generate effective methods of H5N1 air removal and ensure the safety of laboratory personnel, this study was designed to investigate the characteristics of aerosolized H5N1 produced by laboratory manipulations during research studies. Results Normal laboratory procedures used ...

  5. Transmission dynamics of Avian Influenza A virus

    Lu, Lu

    2015-01-01

    Influenza A virus (AIV) has an extremely high rate of mutation. Frequent exchanges of gene segments between different AIV (reassortment) have been responsible for major pandemics in recent human history. The presence of a wild bird reservoir maintains the threat of incursion of AIV into domestic birds, humans and other animals. In this thesis, I addressed unanswered questions of how diverse AIV subtypes (classified according to antigenicity of the two surface proteins, haema...

  6. Aerosolized avian influenza virus by laboratory manipulations

    Li Zhiping

    2012-08-01

    Full Text Available Abstract Background Avian H5N1 influenza viruses present a challenge in the laboratory environment, as they are difficult to collect from the air due to their small size and relatively low concentration. In an effort to generate effective methods of H5N1 air removal and ensure the safety of laboratory personnel, this study was designed to investigate the characteristics of aerosolized H5N1 produced by laboratory manipulations during research studies. Results Normal laboratory procedures used to process the influenza virus were carried out independently and the amount of virus polluting the on-site atmosphere was measured. In particular, zootomy, grinding, centrifugation, pipetting, magnetic stirring, egg inoculation, and experimental zoogenetic infection were performed. In addition, common accidents associated with each process were simulated, including breaking glass containers, syringe injection of influenza virus solution, and rupturing of centrifuge tubes. A micro-cluster sampling ambient air pollution collection device was used to collect air samples. The collected viruses were tested for activity by measuring their ability to induce hemagglutination with chicken red blood cells and to propagate in chicken embryos after direct inoculation, the latter being detected by reverse-transcription PCR and HA test. The results showed that the air samples from the normal centrifugal group and the negative-control group were negative, while all other groups were positive for H5N1. Conclusions Our findings suggest that there are numerous sources of aerosols in laboratory operations involving H5N1. Thus, laboratory personnel should be aware of the exposure risk that accompanies routine procedures involved in H5N1 processing and take proactive measures to prevent accidental infection and decrease the risk of virus aerosol leakage beyond the laboratory.

  7. Structure of NS1A effector domain from the influenza A/Udorn/72 virus

    The structure of the effector domain of the influenza protein NS1, a validated antiviral drug target, has been solved in two space groups. The nonstructural protein NS1A from influenza virus is a multifunctional virulence factor and a potent inhibitor of host immunity. It has two functional domains: an N-terminal 73-amino-acid RNA-binding domain and a C-terminal effector domain. Here, the crystallographic structure of the NS1A effector domain of influenza A/Udorn/72 virus is presented. Structure comparison with the NS1 effector domain from mouse-adapted influenza A/Puerto Rico/8/34 (PR8) virus strain reveals a similar monomer conformation but a different dimer interface. Further analysis and evaluation shows that the dimer interface observed in the structure of the PR8 NS1 effector domain is likely to be a crystallographic packing effect. A hypothetical model of the intact NS1 dimer is presented

  8. Structure of NS1A effector domain from the influenza A/Udorn/72 virus

    Xia, Shuangluo; Monzingo, Arthur F.; Robertus, Jon D., E-mail: jrobertus@mail.utexas.edu [Institute for Cellular and Molecular Biology, Department of Chemistry and Biochemistry, University of Texas, 1 University Station A5300, Austin, TX 78712 (United States)

    2009-01-01

    The structure of the effector domain of the influenza protein NS1, a validated antiviral drug target, has been solved in two space groups. The nonstructural protein NS1A from influenza virus is a multifunctional virulence factor and a potent inhibitor of host immunity. It has two functional domains: an N-terminal 73-amino-acid RNA-binding domain and a C-terminal effector domain. Here, the crystallographic structure of the NS1A effector domain of influenza A/Udorn/72 virus is presented. Structure comparison with the NS1 effector domain from mouse-adapted influenza A/Puerto Rico/8/34 (PR8) virus strain reveals a similar monomer conformation but a different dimer interface. Further analysis and evaluation shows that the dimer interface observed in the structure of the PR8 NS1 effector domain is likely to be a crystallographic packing effect. A hypothetical model of the intact NS1 dimer is presented.

  9. Influenza virus infection, ozone exposure, and fibrogenesis.

    Jakab, G J; Bassett, D J

    1990-05-01

    Oxidant exposure following chemically induced lung injury exacerbates the tendency to develop pulmonary fibrosis. Influenza virus pneumonitis causes severe acute lung damage that, upon resolution, is followed by a persistent alveolitis and parenchymal changes characterized by patchy interstitial pneumonia and collagen deposition in the affected areas. To determine whether oxidant exposure exacerbates the virus-induced alveolitis and residual lung damage, mice were infected by aerosol inhalation with influenza A virus and continuously exposed to 0.5 ppm ozone or ambient air. Noninfected control mice were exposed to either ambient air or ozone. On various days during the first month after infection, groups of mice were sacrificed and their lungs assessed for acute injury (lung lavage albumin, total and differential cell counts, wet/dry ratios, and morphometry). At 30, 60, 90, and 120 days after infection, groups of mice were sacrificed for total and differential lavage cell counts, lung hydroxyproline content, and morphometric analysis. Ozone exposure did not alter the proliferation of virus in the lungs as quantitated by infectious virus titers of lung homogenates at 1, 4, 7, 10, and 15 days after virus infection but mitigated the virus-induced acute lung injury by approximately 50%. After Day 30 a shift in the character of the pulmonary lesions was observed in that continuous exposure to ozone potentiated the postinfluenzal alveolitis and structural changes in the lung parenchyma. Additional studies suggest that the mechanism for the enhanced postinfluenzal lung damage may be related to the oxidant impairing the repair process of the acute influenzal lung damage. These data demonstrate that ozone exposure mitigates acute virus-induced lung injury and potentiates residual lung damage. PMID:2339849

  10. Characterization of influenza virus among influenza like illness cases in Mumbai, India.

    Roy, Soumen; Dahake, Ritwik; Patil, Deepak; Tawde, Shweta; Mukherjee, Sandeepan; Athlekar, Shrikant; Chowdhary, Abhay; Deshmukh, Ranjana

    2014-01-01

    The present study was carried out to monitor influenza viruses by identifying the virus and studying the seasonal variation during 2007-2009 in Mumbai. A total of 193 clinical respiratory samples (nasal and throat swab) were collected from patients having influenza like illness in Mumbai region. One-step real-time reverse-transcriptase PCR (rRTPCR) was used to detect Influenza type A (H1 and H3) and Influenza type B virus. Isolation of the virus was carried out using in vitro system which was further confirmed and typed by hemagglutination assay and hemagglutination inhibition assay. Out of 193 samples 24 (12.4 3%) samples tested positive for influenza virus, of which 13 (6.73 %) were influenza type A virus and 10 (5.18 %) were influenza type B virus, while 1 sample (0.51 %) was positive for both. By culture methods, 3 (1.55 %) viral isolates were obtained. All the three isolates were found to be Influenza type B/Malaysia (Victoria lineage) by Hemagglutination Inhibition Assay. The data generated from the present study reveals that both Influenza type A and B are prevalent in Mumbai with considerable activity. The peak activity was observed during monsoon season. PMID:25674606

  11. New world bats harbor diverse influenza A viruses.

    Suxiang Tong

    Full Text Available Aquatic birds harbor diverse influenza A viruses and are a major viral reservoir in nature. The recent discovery of influenza viruses of a new H17N10 subtype in Central American fruit bats suggests that other New World species may similarly carry divergent influenza viruses. Using consensus degenerate RT-PCR, we identified a novel influenza A virus, designated as H18N11, in a flat-faced fruit bat (Artibeus planirostris from Peru. Serologic studies with the recombinant H18 protein indicated that several Peruvian bat species were infected by this virus. Phylogenetic analyses demonstrate that, in some gene segments, New World bats harbor more influenza virus genetic diversity than all other mammalian and avian species combined, indicative of a long-standing host-virus association. Structural and functional analyses of the hemagglutinin and neuraminidase indicate that sialic acid is not a ligand for virus attachment nor a substrate for release, suggesting a unique mode of influenza A virus attachment and activation of membrane fusion for entry into host cells. Taken together, these findings indicate that bats constitute a potentially important and likely ancient reservoir for a diverse pool of influenza viruses.

  12. Immunomodulatory Activity of Red Ginseng against Influenza A Virus Infection

    Jong Seok Lee; Hye Suk Hwang; Eun-Ju Ko; Yu-Na Lee; Young-Man Kwon; Min-Chul Kim; Sang-Moo Kang

    2014-01-01

    Ginseng herbal medicine has been known to have beneficial effects on improving human health. We investigated whether red ginseng extract (RGE) has preventive effects on influenza A virus infection in vivo and in vitro. RGE was found to improve survival of human lung epithelial cells upon influenza virus infection. Also, RGE treatment reduced the expression of pro-inflammatory genes (IL-6, IL-8) probably in part through interference with the formation of reactive oxygen species by influenza A...

  13. Neuraminidase inhibitors for influenza B virus infection: efficacy and resistance

    Burnham, Andrew J.; Baranovich, Tatiana; Govorkova, Elena A.

    2013-01-01

    Many aspects of the biology and epidemiology of influenza B viruses are far less studied than for influenza A viruses, and one of these aspects is effectiveness and resistance to the clinically available antiviral drugs, the neuraminidase (NA) inhibitors (NAIs). Acute respiratory infections are one of the leading causes of death in children and adults, and influenza is among the few respiratory infections that can be prevented and treated by vaccination and antiviral treatment. Recent data ha...

  14. Characterization of two influenza A viruses from a pilot whale.

    Hinshaw, V S; Bean, W J; Geraci, J.; Fiorelli, P; Early, G.; Webster, R G

    1986-01-01

    Influenza A viruses of the H13N2 and H13N9 subtypes were isolated from the lung and hilar node of a pilot whale. Serological, molecular, and biological analyses indicate that the whale isolates are closely related to the H13 influenza viruses from gulls.

  15. Avian Influenza Viruses in Water Birds, Africa 1

    Gaidet, Nicolas; Dodman, Tim; Caron, Alexandre; Balança, Gilles; Desvaux, Stephanie; Goutard, Flavie; Cattoli, Giovanni; Lamarque, François; Hagemeijer, Ward; Monicat, François

    2007-01-01

    We report the first large-scale surveillance of avian influenza viruses in water birds conducted in Africa. This study shows evidence of avian influenza viruses in wild birds, both Eurasian and Afro-tropical species, in several major wetlands of Africa.

  16. radioprotective and interferonogenic characteristics of influenza virus vaccine

    Different methods of prophylactic treatment with influenza virus vaccina increase survival of irradiated mice and hamsters by 25-55% as compared to unprotected ones. Higher radioresistance occurs in the same time intervals as a rise of interferon in the blood after immunization with influenza virus vaccine. 7 refs.; 2 figs.; 2 tabs

  17. Immunomodulatory Activity of Red Ginseng against Influenza A Virus Infection

    Jong Seok Lee

    2014-01-01

    Full Text Available Ginseng herbal medicine has been known to have beneficial effects on improving human health. We investigated whether red ginseng extract (RGE has preventive effects on influenza A virus infection in vivo and in vitro. RGE was found to improve survival of human lung epithelial cells upon influenza virus infection. Also, RGE treatment reduced the expression of pro-inflammatory genes (IL-6, IL-8 probably in part through interference with the formation of reactive oxygen species by influenza A virus infection. Long-term oral administration of mice with RGE showed multiple immunomodulatory effects such as stimulating antiviral cytokine IFN-γ production after influenza A virus infection. In addition, RGE administration in mice inhibited the infiltration of inflammatory cells into the bronchial lumens. Therefore, RGE might have the potential beneficial effects on preventing influenza A virus infections via its multiple immunomodulatory functions.

  18. Virulence of Avian Influenza A Viruses for Squirrel Monkeys

    Murphy, Brian R.; Hinshaw, Virginia S.; Sly, D. Lewis; London, William T.; Hosier, Nanette T.; Wood, Frank T.; Webster, Robert G.; Chanock, Robert M.

    1982-01-01

    Ten serologically distinct avian influenza A viruses were administered to squirrel monkeys and hamsters to compare their replication and virulence with those of human influenza A virus, A/Udorn/307/72 (H3N2). In squirrel monkeys, the 10 avian influenza A viruses exhibited a spectrum of replication and virulence. The levels of virus replication and clinical response were closely correlated. Two viruses, A/Mallard/NY/6874/78 (H3N2) and A/Pintail/Alb/121/79 (H7N8), resembled the human virus in their level and duration of replication and in their virulence. At the other end of the spectrum, five avian viruses were restricted by 100- to 10,000-fold in replication in the upper and lower respiratory tract and were clearly attenuated compared with the human influenza virus. In hamsters, the 10 viruses exhibited a spectrum of replication in the nasal turbinates, ranging from viruses that replicated as efficiently as the human virus to those that were 8,000- fold restricted. Since several avian viruses were closely related serologically to human influenza viruses, studies were done to confirm the avian nature of these isolates. Each of the avian viruses plaqued efficiently at 42°C, a restrictive temperature for replication of human influenza A viruses. Avian strains that had replicated either very efficiently or very poorly in squirrel monkeys still grew to high titer in the intestinal tracts of ducks, a tropism characteristic of avian, but not mammalian, influenza viruses. These observations indicate that some avian influenza A viruses grow well and cause disease in a primate host, whereas other avian viruses are very restricted in this host. These findings also provide a basis for determining the gene or genes involved in the restriction of replication that is observed with the attenuated avian viruses. Application of such information may allow the preparation of reassortant viruses derived from a virulent human influenza virus and an attenuated avian virus for possible

  19. Novel reassortant swine influenza viruses are circulating in Danish pigs

    Breum, Solvej Østergaard; Hjulsager, Charlotte Kristiane; Trebbien, Ramona;

    The Danish surveillance program for influenza A virus in pigs has revealed that two novel reassortant swine influenza viruses may now be circulating in the Danish swine population, since they each have been detected in at least two submissions from different herds in 2011 as well as in 2012. One of...... the reassortant viruses comprised a HA gene similar to H1 of H1N1 avian-like swine influenza virus (SIV) and a NA gene most closely related to N2 gene of human H3N2 influenza virus that circulated in humans in the mid 1990s. The internal genes of this reassortant virus with the subtype H1avN2hu all...... pandemic H1N1pdm09 influenza virus lineage. Swine influenza virus with a similar subtype to H1pdm09N2sw has previously been found in pigs in Italy and Germany. Detailed analyses of viral genes will further elucidate the relationship between these new swine influenza viruses found in the different countries...

  20. The challenges of avian influenza virus: mechanism, epidemiology and control

    George F. GAO; Pang-Chui SHAW

    2009-01-01

    @@ Early 2009, eight human infection cases of H5N1 highly pathogenic avian influenza (HPAI) virus, with 5 death cases, were reported in China. This again made the world alert on a possible pandemic worldwide, probably caused by avian-origin influenza virus. Again H5N1 is in the spotlight of the world, not only for the scientists but also for the ordinary people. How much do we know about this virus? Where will this virus go and where did it come? Can we avoid a possible pandemic of influenza? Will the human beings conquer this devastating agent? Obviously we can list more questions than we know the answers.

  1. Current Approaches for Diagnosis of Influenza Virus Infections in Humans

    Vemula, Sai Vikram; Zhao, Jiangqin; Liu, Jikun; Wang, Xue; Biswas, Santanu; Hewlett, Indira

    2016-01-01

    Despite significant advancement in vaccine and virus research, influenza continues to be a major public health concern. Each year in the United States of America, influenza viruses are responsible for seasonal epidemics resulting in over 200,000 hospitalizations and 30,000–50,000 deaths. Accurate and early diagnosis of influenza viral infections are critical for rapid initiation of antiviral therapy to reduce influenza related morbidity and mortality both during seasonal epidemics and pandemics. Several different approaches are currently available for diagnosis of influenza infections in humans. These include viral isolation in cell culture, immunofluorescence assays, nucleic acid amplification tests, immunochromatography-based rapid diagnostic tests, etc. Newer diagnostic approaches are being developed to overcome the limitations associated with some of the conventional detection methods. This review discusses diagnostic approaches currently available for detection of influenza viruses in humans. PMID:27077877

  2. Influenza B Virus: Some Features of Clinical Findings and Etiotropic Treatment

    O. V. Maltsev; I. S. Grishin; E. V. Peredelsky; N. I. Lvov; K. V. Zhdanov

    2013-01-01

    Since January 1997 till March 2009 492 patients with a confirmed diagnosis of influenza A virus and influenza B virus underwent work-up in Military Medical Academy. It is established that the clinical findings of influenza B virus are accurately different from the clinical findings of influenza A virus. Influenza B virus is characterized by more prolonged fever, lower incidence and duration of some respiratory syndromes and fewer sequelae. The influence of etiotropic drugs and early interfero...

  3. Influenza Virus Resistance to Antiviral Agents: A Plea for Rational Use

    Poland, Gregory A.; Jacobson, Robert M.; Ovsyannikova, Inna G.

    2009-01-01

    Although influenza vaccine can prevent influenza virus infection, the only therapeutic options to treat influenza virus infection are antiviral agents. At the current time, nearly all influenza A/H3N2 viruses and a percentage of influenza A/H1N1 viruses are adamantane resistant, which leaves only neuraminidase inhibitors available for treatment of infection with these viruses. In December 2008, the Centers for Disease Control and Prevention released new data demonstrating that a high percenta...

  4. Avian influenza in shorebirds: experimental infection of ruddy turnstones (Arenaria interpres) with avian influenza virus

    Hall, Jeffrey S.; Krauss, Scott; Franson, J. Christian; TeSlaa, Joshua L.; Nashold, Sean W.; Stallknecht, David E.; Webby, Richard J.; Webster, Robert G.

    2013-01-01

    Background: Low pathogenic avian influenza viruses (LPAIV) have been reported in shorebirds, especially at Delaware Bay, USA, during spring migration. However, data on patterns of virus excretion, minimal infectious doses, and clinical outcome are lacking. The ruddy turnstone (Arenaria interpres) is the shorebird species with the highest prevalence of influenza virus at Delaware Bay. Objectives: The primary objective of this study was to experimentally assess the patterns of influenza virus excretion, minimal infectious doses, and clinical outcome in ruddy turnstones. Methods: We experimentally challenged ruddy turnstones using a common LPAIV shorebird isolate, an LPAIV waterfowl isolate, or a highly pathogenic H5N1 avian influenza virus. Cloacal and oral swabs and sera were analyzed from each bird. Results: Most ruddy turnstones had pre-existing antibodies to avian influenza virus, and many were infected at the time of capture. The infectious doses for each challenge virus were similar (103·6–104·16 EID50), regardless of exposure history. All infected birds excreted similar amounts of virus and showed no clinical signs of disease or mortality. Influenza A-specific antibodies remained detectable for at least 2 months after inoculation. Conclusions: These results provide a reference for interpretation of surveillance data, modeling, and predicting the risks of avian influenza transmission and movement in these important hosts.

  5. Avian influenza virus risk assessment in falconry

    Lüschow Dörte; Lierz Peter; Jansen Andreas; Harder Timm; Hafez Hafez; Kohls Andrea; Schweiger Brunhilde; Lierz Michael

    2011-01-01

    Abstract Background There is a continuing threat of human infections with avian influenza viruses (AIV). In this regard falconers might be a potential risk group because they have close contact to their hunting birds (raptors such as falcons and hawks) as well as their avian prey such as gulls and ducks. Both (hunting birds and prey birds) seem to be highly susceptible to some AIV strains, especially H5N1. We therefore conducted a field study to investigate AIV infections in falconers, their ...

  6. The variable codons of H5N1 avian influenza A virus haemagglutinin genes

    Mark; J.GIBBS; Robert; W.MURPHY

    2008-01-01

    We investigated the selection pressures on the haemagglutinin genes of H5N1 avian influenza viruses using fixed effects likelihood models. We found evidence of positive selection in the sequences from isolates from 1997 to 2007, except viruses from 2000. The haemagglutinin sequences of viruses from southeast Asia, Hong Kong and mainland China were the most polymorphic and had similar nonsyn-onymous profiles. Some sites were positively selected in viruses from most regions and a few of these sites displayed different amino acid patterns. Selection appeared to produce different outcomes in vi-ruses from Europe, Africa and Russia and from different host types. One position was found to be positively selected for human isolates only. Although the functions of some positively selected posi-tions are unknown, our analysis provided evidence of different temporal, spatial and host adaptations for H5N1 avian influenza viruses.

  7. Avian influenza virus and free-ranging wild birds

    Dierauf, Leslie A.; Karesh, W.B.; Ip, Hon S.; Gilardi, K.V.; Fischer, John R.

    2006-01-01

    Recent media and news reports and other information implicate wild birds in the spread of highly pathogenic avian influenza in Asia and Eastern Europe. Although there is little information concerning highly pathogenic avian influenza viruses in wild birds, scientists have amassed a large amount of data on low-pathogenicity avian influenza viruses during decades of research with wild birds. This knowledge can provide sound guidance to veterinarians, public health professionals, the general public, government agencies, and other entities with concerns about avian influenza.

  8. Antigenic characterization of influenza viruses produced using synthetic DNA and novel backbones.

    Suphaphiphat, Pirada; Whittaker, Lynne; De Souza, Ivna; Daniels, Rodney S; Dormitzer, Philip R; McCauley, John W; Settembre, Ethan C

    2016-07-12

    The global system for manufacturing seasonal influenza vaccines has been developed to respond to the natural evolution of influenza viruses, but the problem of antigenic mismatch continues to be a challenge in certain years. In some years, mismatches arise naturally due to the antigenic drift of circulating viruses after vaccine strain selection has already been made. In other years, antigenic differences between the vaccine virus and circulating viruses are introduced as part of the current system, which relies on the use of egg-adapted isolates as a starting material for candidate vaccine viruses (CVVs). Improving the current process for making vaccine viruses can provide great value. We have previously established a synthetic approach for rapidly generating influenza viruses in a vaccine-approved Madin Darby canine kidney (MDCK) cell line using novel, high-growth backbones that increase virus rescue efficiency and antigen yield. This technology also has the potential to produce viruses that maintain antigenic similarity to the intended reference viruses, depending on the hemagglutinin (HA) and neuraminidase (NA) sequences used for gene synthesis. To demonstrate this utility, we generated a panel of synthetic viruses using HA and NA sequences from recent isolates and showed by hemagglutination inhibition (HI) tests that all synthetic viruses were antigenically-like their conventional egg- or cell-propagated reference strains and there was no impact of the novel backbones on antigenicity. This synthetic approach can be used for the efficient production of CVVs that may be more representative of circulating viruses and may be used for both egg- and cell-based vaccine manufacturing platforms. When combined with mammalian cell culture technology for antigen production, synthetic viruses generated using HA and NA sequences from a non-egg-adapted prototype can help to reduce the potential impact of antigenic differences between vaccine virus and circulating viruses on

  9. The global antigenic diversity of swine influenza A viruses

    Lewis, Nicola S.; Russell, Colin A.; Langat, Pinky; Tavis K Anderson; Berger, Kathryn; Bielejec, Filip; Burke, David F.; Dudas, Gytis; Fonville, Judith M; Fouchier, Ron AM; Kellam, Paul; Koel, Bjorn F; Lemey, Philippe; Nguyen, Tung; Nuansrichy, Bundit

    2016-01-01

    Swine influenza presents a substantial disease burden for pig populations worldwide and poses a potential pandemic threat to humans. There is considerable diversity in both H1 and H3 influenza viruses circulating in swine due to the frequent introductions of viruses from humans and birds coupled with geographic segregation of global swine populations. Much of this diversity is characterized genetically but the antigenic diversity of these viruses is poorly understood. Critically, the antigeni...

  10. Rapid preparation of mutated influenza hemagglutinins for influenza virus pandemic prevention

    Nishioka, Ryosuke; Satomura, Atsushi; Yamada, Junki; Kuroda, Kouichi; Ueda, Mitsuyoshi

    2016-01-01

    Influenza viruses have periodically caused pandemic due to frequent mutation of viral proteins. Influenza viruses have two major membrane glycoproteins: hemagglutinin (HA) and neuraminidase (NA). Hemagglutinin plays a crucial role in viral entry, while NA is involved in the process of a viral escape. In terms of developing antiviral drugs, HA is a more important target than NA in the prevention of pandemic, since HA is likely to change the host specificity of a virus by acquiring mutations, t...

  11. Molecular diagnostics of Avian influenza virus

    Petrović Tamaš

    2006-01-01

    Full Text Available The success of supervizing an infectious disease depends on the ability for speedy detection and characterization of the cause and the forming of a corresponding system for examining the success of control implemented in order to prevent a recurrence of the disease. Since influenza viruses continue to circle, causing significant morbidity and mortality both among the human population and among animals all over the world, it is essential to secure the timely identification and monitoring of the strains that are in circulation. The speedy detection and characterization of new highly-virulent varieties is one of the priorities of the World Health Organization monitoring network. The implementation of molecular methods has an increasingly significant role in diagnostics and the monitoring of the influenza virus. Among a large number of molecular methods, the one particularly in use is the reverse transcription-polimerase chain reaction (PT-PCR. Technological progress in the area of the conducting of molecular methods has enabled that we can prove, in one day, using the RT-PCR method even very small quantities of the infective agent in a sample. In an obtained PCR product, we can relatively easily establish the nucleotide sequence, a detailed analysis and molecular epidemiology of the circulating strains. The molecular diagnostics procedure (RT-PCR is based on the correct choice or designing of primers depending on the desired knowledge. In order to obtain a specific diagnosis of influenza A, B or C, primers are used which multiply internal genes, such as the nucleoprotein (NP or matrix gene (M, because these are genes that are highly conserved among the virus types. In the event that we are interested in the subtype of influenza A, after obtaining a positive reaction, primers for genes of surface antigens are selected, such as hemagglutinin. Following the correct detection of the H subtype, it is possible to establish the virus virulence through the

  12. The high susceptibility of turkeys to influenza viruses of different origins implies their importance as potential intermediate hosts.

    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

  13. Monitoring Avian Influenza A(H7N9) Virus through National Influenza-like Illness Surveillance, China

    Xu, Cuiling; Havers, Fiona; Wang, Lijie; Tao CHEN; Shi, Jinghong; Wang, Dayan; YANG Jing; Lei YANG; Widdowson, Marc-Alain; Shu, Yuelong

    2013-01-01

    In China during March 4–April 28, 2013, avian influenza A(H7N9) virus testing was performed on 20,739 specimens from patients with influenza-like illness in 10 provinces with confirmed human cases: 6 (0.03%) were positive, and increased numbers of unsubtypeable influenza-positive specimens were not seen. Careful monitoring and rapid characterization of influenza A(H7N9) and other influenza viruses remain critical.

  14. Relationship of influenza virus infection to associated infections in children who present with influenza-like symptoms

    Norowitz, Yitzchok M.; Kohlhoff, Stephan; Smith-Norowitz, Tamar A

    2016-01-01

    Background Influenza virus is a major health care burden and is associated with significant morbidity and mortality. Data on morbidity and complications (pneumonia, otitis media) related to influenza virus infection in primary care settings are limited with reports mainly obtained from hospital settings. We assessed the prevalence of complications from viral/bacterial infections in influenza- positive compared with influenza- negative children presenting with influenza-like illness (ILI) in a...

  15. Platelet activation and aggregation promote lung inflammation and influenza virus pathogenesis.

    Le, Vuong Ba; Schneider, Jochen; Boergeling, Yvonne; Berri, Fatma; Ducatez, Mariette; GUERIN, Jean-Luc; Adrian, Iris; Errazuriz-Cerda, Elisabeth; frasquilho, sonia; Antunes, Laurent; Lina, Bruno; Bordet, Jean-Claude; Jandrot-Perrus, Martine; Ludwig, Stephan; Riteau, Beatrice

    2015-01-01

    RATIONALE: The hallmark of severe influenza virus infection is excessive inflammation of the lungs. Platelets are activated during influenza, but their role in influenza virus pathogenesis and inflammatory responses is unknown. OBJECTIVES: To determine the role of platelets during influenza A virus infections and propose new therapeutics against influenza. METHODS: We used targeted gene deletion approaches and pharmacologic interventions to investigate the role of platelets during influenza v...

  16. Avian Influenza: Mixed Infections and Missing Viruses

    David E. Wentworth

    2013-08-01

    Full Text Available A high prevalence and diversity of avian influenza (AI viruses were detected in a population of wild mallards sampled during summer 2011 in California, providing an opportunity to compare results obtained before and after virus culture. We tested cloacal swab samples prior to culture by matrix real-time PCR, and by amplifying and sequencing a 640bp portion of the hemagglutinin (HA gene. Each sample was also inoculated into embryonated chicken eggs, and full genome sequences were determined for cultured viruses. While low matrix Ct values were a good predictor of virus isolation from eggs, samples with high or undetectable Ct values also yielded isolates. Furthermore, a single passage in eggs altered the occurrence and detection of viral strains, and mixed infections (different HA subtypes were detected less frequently after culture. There is no gold standard or perfect reference comparison for surveillance of unknown viruses, and true negatives are difficult to distinguish from false negatives. This study showed that sequencing samples prior to culture increases the detection of mixed infections and enhances the identification of viral strains and sequences that may have changed or even disappeared during culture.

  17. Cocirculation of avian H9N2 and contemporary "human" H3N2 influenza A viruses in pigs in southeastern China: Potential for genetic reassortment?

    Peiris, J. S. M.; Guan, Y.; Markwell, D; Ghose, P.; Webster, R G; Shortridge, K. F.

    2001-01-01

    Pigs are permissive to both human and avian influenza viruses and have been proposed to be an intermediate host for the genesis of pandemic influenza viruses through reassortment or adaptation of avian viruses. Prospective virological surveillance carried out between March 1998 and June 2000 in Hong Kong, Special Administrative Region, People's Republic of China, on pigs imported from southeastern China, provides the first evidence of interspecies transmission of avian H9N2 viruses to pigs an...

  18. Dogs are highly susceptible to H5N1 avian influenza virus

    Chen, Ying; Zhong, Gongxun; Wang, Guojun; Deng, Guohua; Li, Yanbing; Shi, Jianzhong; Zhang, Zhuo; Guan, Yuntao; Jiang, Yongping; Bu, Zhigao; Kawaoka, Yoshihiro; Chen, Hualan

    2010-01-01

    Replication of avian influenza viruses (AIVs) in dogs may facilitate their adaptation in humans; however, the data to date on H5N1 influenza virus infection in dogs are conflicting. To elucidate the susceptibility of dogs to this pathogen, we infected two groups of 6 beagles with 106 50% egg-infectious dose of H5N1 AIV A/bar-headed goose/Qinghai/3/05 (BHG/QH/3/05) intranasally (i.n.) and intratracheally (i.t.), respectively. The dogs showed disease symptoms, including anorexic, fever, conjunc...

  19. A competitive-inhibiton radioimmunoassay for influenza virus envelope antigens

    A double-antibody competitive-inhibition radioimmunoassay for influenza virus envelope antigens is described. A viral antigen preparation from influenza A virus recombinant MRC11 [antigenically identical to A/Port Chalmers/1/73 (H3N2)] consisting of haemagglutinin and neuraminidase was labelled with radioiodine. Rabbit antisera were allowed to react with the labelled antigen and the resultant antigen-antibody complexes were precipitated with the appropriate antiglobulin. The competitive-inhibition radioimmunoassay very sensitively elucidated differences even among closely related influenza virus strains. Attempts have been made to eliminate neuraminidase from radioimmunoprecipitation to obtain a competitive-inhibition radioimmunoassay system for haemagglutinin alone. (author)

  20. Quantification of Influenza Virus RNA in Aerosols in Patient Rooms

    Leung, Nancy H. L.; Zhou, Jie; Daniel K W Chu; Yu, Han; William G. Lindsley; Beezhold, Donald H.; Yen, Hui-Ling; Li, Yuguo; Seto, Wing-Hong; Peiris, Joseph S. M.; Cowling, Benjamin J

    2016-01-01

    Background The potential for human influenza viruses to spread through fine particle aerosols remains controversial. The objective of our study was to determine whether influenza viruses could be detected in fine particles in hospital rooms. Methods and Findings We sampled the air in 2-bed patient isolation rooms for four hours, placing cyclone samplers at heights of 1.5m and 1.0m. We collected ten air samples each in the presence of at least one patient with confirmed influenza A virus infec...

  1. A Review of Evidence that Equine Influenza Viruses Are Zoonotic.

    Xie, Tai; Anderson, Benjamin D; Daramragchaa, Ulziimaa; Chuluunbaatar, Maitsetset; Gray, Gregory C

    2016-01-01

    Among scientists, there exist mixed opinions whether equine influenza viruses infect man. In this report, we summarize a 2016 systematic and comprehensive review of the English, Chinese, and Mongolian scientific literature regarding evidence for equine influenza virus infections in man. Searches of PubMed, Web of Knowledge, ProQuest, CNKI, Chongqing VIP Database, Wanfang Data and MongolMed yielded 2831 articles, of which 16 met the inclusion criteria for this review. Considering these 16 publications, there was considerable experimental and observational evidence that at least H3N8 equine influenza viruses have occasionally infected man. In this review we summarize the most salient scientific reports. PMID:27420100

  2. Preserved antiviral adaptive immunity following polyclonal antibody immunotherapy for severe murine influenza infection

    Stevens, Natalie E.; Hatjopolous, Antoinette; Fraser, Cara K.; Alsharifi, Mohammed; Diener, Kerrilyn R.; Hayball, John D.

    2016-01-01

    Passive immunotherapy may have particular benefits for the treatment of severe influenza infection in at-risk populations, however little is known of the impact of passive immunotherapy on the formation of memory responses to the virus. Ideally, passive immunotherapy should attenuate the severity of infection while still allowing the formation of adaptive responses to confer protection from future exposure. In this study, we sought to determine if administration of influenza-specific ovine polyclonal antibodies could inhibit adaptive immune responses in a murine model of lethal influenza infection. Ovine polyclonal antibodies generated against recombinant PR8 (H1N1) hemagglutinin exhibited potent prophylactic capacity and reduced lethality in an established influenza infection, particularly when administered intranasally. Surviving mice were also protected against reinfection and generated normal antibody and cytotoxic T lymphocyte responses to the virus. The longevity of ovine polyclonal antibodies was explored with a half-life of over two weeks following a single antibody administration. These findings support the development of an ovine passive polyclonal antibody therapy for treatment of severe influenza infection which does not affect the formation of subsequent acquired immunity to the virus. PMID:27380890

  3. Preserved antiviral adaptive immunity following polyclonal antibody immunotherapy for severe murine influenza infection.

    Stevens, Natalie E; Hatjopolous, Antoinette; Fraser, Cara K; Alsharifi, Mohammed; Diener, Kerrilyn R; Hayball, John D

    2016-01-01

    Passive immunotherapy may have particular benefits for the treatment of severe influenza infection in at-risk populations, however little is known of the impact of passive immunotherapy on the formation of memory responses to the virus. Ideally, passive immunotherapy should attenuate the severity of infection while still allowing the formation of adaptive responses to confer protection from future exposure. In this study, we sought to determine if administration of influenza-specific ovine polyclonal antibodies could inhibit adaptive immune responses in a murine model of lethal influenza infection. Ovine polyclonal antibodies generated against recombinant PR8 (H1N1) hemagglutinin exhibited potent prophylactic capacity and reduced lethality in an established influenza infection, particularly when administered intranasally. Surviving mice were also protected against reinfection and generated normal antibody and cytotoxic T lymphocyte responses to the virus. The longevity of ovine polyclonal antibodies was explored with a half-life of over two weeks following a single antibody administration. These findings support the development of an ovine passive polyclonal antibody therapy for treatment of severe influenza infection which does not affect the formation of subsequent acquired immunity to the virus. PMID:27380890

  4. Animal Models for Influenza Virus Pathogenesis and Transmission

    Anice C. Lowen

    2010-07-01

    Full Text Available Influenza virus infection of humans results in a respiratory disease that ranges in severity from sub-clinical infection to primary viral pneumonia that can result in death. The clinical effects of infection vary with the exposure history, age and immune status of the host, and also the virulence of the influenza strain. In humans, the virus is transmitted through either aerosol or contact-based transfer of infectious respiratory secretions. As is evidenced by most zoonotic influenza virus infections, not all strains that can infect humans are able to transmit from person-to-person. Animal models of influenza are essential to research efforts aimed at understanding the viral and host factors that contribute to the disease and transmission outcomes of influenza virus infection in humans. These models furthermore allow the pre-clinical testing of antiviral drugs and vaccines aimed at reducing morbidity and mortality in the population through amelioration of the virulence or transmissibility of influenza viruses. Mice, ferrets, guinea pigs, cotton rats, hamsters and macaques have all been used to study influenza viruses and therapeutics targeting them. Each model presents unique advantages and disadvantages, which will be discussed herein.

  5. El virus influenza y la gripe aviar Influenza virus and avian flu

    Libia Herrero-Uribe

    2008-03-01

    Full Text Available En este artículo se presenta una revisión del virus influenza,su biología,sus mecanismos de variación antigénica,las pandemias que ha producido y la prevención mediante las vacunas y medicamentos antivirales.Se analizan las razones por las cuales aparece el virus H5N1 que produce la fiebre aviar en humanos,la patogénesis de este virus y las estrategias para su prevención.Se informa sobre el plan de preparación para la pandemia en los niveles nacional e internacional.This article presents a review of Influenza virus,its biology,its mechanism of antigenic variation and its prevention by vaccination and the use of antivirals.The pandemics produced by this virus through history are presented.The appearance of the avian flu virus H5N1 is analyzed and its pathogenesis and strategies of prevention are discussed.National and international information about pandemic preparedness is presented.

  6. Influenza A Virus Entry Inhibitors Targeting the Hemagglutinin

    Shuwen Liu; Jie Yang; Xintian Shen; Minmin Li

    2013-01-01

    Influenza A virus (IAV) has caused seasonal influenza epidemics and influenza pandemics, which resulted in serious threat to public health and socioeconomic impacts. Until now, only 5 drugs belong to two categories are used for prophylaxis and treatment of IAV infection. Hemagglutinin (HA), the envelope glycoprotein of IAV, plays a critical role in viral binding, fusion and entry. Therefore, HA is an attractive target for developing anti‑IAV drugs to block the entry step of IAV infection. Her...

  7. Pathobiology of avian influenza virus infections in wild birds

    Individual avian Influenza (AI) viruses vary in their ability to produce infection, disease and death in different bird species. Based on the pathobiological features in chickens, AI viruses (AIV) are categorized as low pathogenicity (LPAI) or high pathogenicity (HPAI) viruses, and can be of any of...

  8. Influenza-associated encephalopathy: no evidence for neuroinvasion by influenza virus nor for reactivation of human herpesvirus 6 or 7.

    van Zeijl, J.H.; Bakkers, J.; Wilbrink, B.; Melchers, W.J.; Mullaart, R.A.; Galama, J.M.

    2005-01-01

    During 2 consecutive influenza seasons we investigated the presence of influenza virus, human herpesvirus (HHV) type 6, and HHV-7 in cerebrospinal fluid samples from 9 white children suffering from influenza-associated encephalopathy. We conclude that it is unlikely that neuroinvasion by influenza v

  9. Practical aspects of vaccination of poultry against avian influenza virus

    Although little has changed in vaccine technology for avian influenza virus (AIV) in the past 20 years, the approach to vaccination of poultry (chickens, turkeys and ducks) for avian influenza has evolved as highly pathogenic (HP) AIV has become endemic in several regions of the world. Vaccination f...

  10. Influenza A virus pathogenesis and vaccination in swine

    Swine influenza is an acute respiratory disease of pigs that is characterized by fever followed by lethargy, anorexia, and serous nasal discharge. The disease progresses rapidly and may be complicated when associated with other respiratory pathogens. Influenza A virus (IAV) is one of the most preval...

  11. The quest of influenza A viruses for new hosts.

    Liu, M; Guan, Y; Peiris, M; He, S; Webby, R J; Perez, D; Webster, R G

    2003-01-01

    There is increasing evidence that stable lineages of influenza viruses are being established in chickens. H9N2 viruses are established in chickens in Eurasia, and there are increasing reports of H3N2, H6N1, and H6N2 influenza viruses in chickens both in Asia and North America. Surveillance in a live poultry market in Nanchang, South Central China, reveals that influenza viruses were isolated form 1% of fecal samples taken from healthy poultry over the course of 16 months. The highest isolation rates were from chickens (1.3%) and ducks (1.2%), followed by quail (0.8%), then pigeon (0.5%). H3N6, H9N2, H2N9, and H4N6 viruses were isolated from multiple samples, while single isolates of H1N1, H3N2, and H3N3 viruses were made. Representatives of each virus subtype were experimentally inoculated into both quail and chickens. All the viruses replicated in the trachea of quail, but efficient replication in chickens was confined to 25% of the tested isolates. In quail, these viruses were shed primarily by the aerosol route, raising the possibility that quail may be the "route modulator" that changes the route of transmission of influenza viruses from fecal-oral to aerosol transmission. Thus, quail may play an important role in the natural history of influenza viruses. The pros and cons of the use of inactivated and recombinant fowl pox-influenza vaccines to control the spread of avian influenza are also evaluated. PMID:14575076

  12. Cross-Species Infectivity of H3N8 Influenza Virus in an Experimental Infection in Swine

    Solórzano, Alicia; Foni, Emanuela; Córdoba, Lorena; Baratelli, Massimiliano; Razzuoli, Elisabetta; Bilato, Dania; Martín del Burgo, María Ángeles; Perlin, David S.; Martínez, Jorge; Martínez-Orellana, Pamela; Fraile, Lorenzo; Chiapponi, Chiara; Amadori, Massimo; del Real, Gustavo; Montoya, María

    2015-01-01

    Avian influenza A viruses have gained increasing attention due to their ability to cross the species barrier and cause severe disease in humans and other mammal species as pigs. H3 and particularly H3N8 viruses, are highly adaptive since they are found in multiple avian and mammal hosts. H3N8 viruses have not been isolated yet from humans; however, a recent report showed that equine influenza A viruses (IAVs) can be isolated from pigs, although an established infection has not been observed t...

  13. Prevention and Treatment of Avian Influenza A Viruses in People

    ... this? Submit What's this? Submit Button Past Newsletters Prevention and Treatment of Avian Influenza A Viruses in ... Recommend on Facebook Tweet Share Compartir The Best Prevention is to Avoid Sources of Exposure Currently, the ...

  14. Isolation of influenza viruses in MDCK 33016PF cells and clearance of contaminating respiratory viruses.

    Roth, Bernhard; Mohr, Hannah; Enders, Martin; Garten, Wolfgang; Gregersen, Jens-Peter

    2012-01-11

    This paper summarizes results obtained by multiplex PCR screening of human clinical samples for respiratory viruses and corresponding data obtained after passaging of virus-positive samples in MDCK 33016PF cells. Using the ResPlexII v2.0 (Qiagen) multiplex PCR, 393 positive results were obtained in 468 clinical samples collected during an influenza season in Germany. The overall distribution of positive results was influenza A 42.0%, influenza B 38.7%, adenovirus 1.5%, bocavirus 0.5%, coronavirus 3.3%, enterovirus 5.6%, metapneumovirus 1.0%, parainfluenza virus 0.8%, rhinovirus 4.1%, and respiratory syncytial virus (RSV) 2.5%. Double infections of influenza virus together with another virus were found for adenovirus B and E, bocavirus, coronavirus, enterovirus and for rhinovirus. These other viruses were rapidly lost upon passages in MDCK 33016PF cells and under conditions as applied to influenza virus passaging. Clinical samples, in which no influenza virus but other viruses were found, were also subject to passages in MDCK 33016PF cells. Using lower inoculum dilutions than those normally applied for preparations containing influenza virus (total dilution of the original sample of ∼10(4)), the positive results for the different viruses turned negative already after 2 or 3 passages in MDCK 33016PF cells. These results demonstrate that, under practical conditions as applied to grow influenza viruses, contaminating viruses can be effectively removed by passages in MDCK cells. In combination with their superior isolation efficiency, MDCK cells appear highly suitable to be used as an alternative to embryonated eggs to isolate and propagate influenza vaccine candidate viruses. PMID:22119922

  15. Multi-spectral fluorescent reporter influenza viruses (Color-flu) as powerful tools for in vivo studies.

    Fukuyama, Satoshi; Katsura, Hiroaki; Zhao, Dongming; Ozawa, Makoto; Ando, Tomomi; Shoemaker, Jason E; Ishikawa, Izumi; Yamada, Shinya; Neumann, Gabriele; Watanabe, Shinji; Kitano, Hiroaki; Kawaoka, Yoshihiro

    2015-01-01

    Seasonal influenza A viruses cause annual epidemics of respiratory disease; highly pathogenic avian H5N1 and the recently emerged H7N9 viruses cause severe infections in humans, often with fatal outcomes. Although numerous studies have addressed the pathogenicity of influenza viruses, influenza pathogenesis remains incompletely understood. Here we generate influenza viruses expressing fluorescent proteins of different colours ('Color-flu' viruses) to facilitate the study of viral infection in in vivo models. On adaptation to mice, stable expression of the fluorescent proteins in infected animals allows their detection by different types of microscopy and by flow cytometry. We use this system to analyse the progression of viral spread in mouse lungs, for live imaging of virus-infected cells, and for differential gene expression studies in virus antigen-positive and virus antigen-negative live cells in the lungs of Color-flu-infected mice. Collectively, Color-flu viruses are powerful tools to analyse virus infections at the cellular level in vivo to better understand influenza pathogenesis. PMID:25807527

  16. The Irrationality of GOF Avian Influenza Virus Research

    Wain-Hobson, Simon

    2014-01-01

    The last two and a half years have witnessed a curious debate in virology characterized by a remarkable lack of discussion. It goes by the misleading epithet “gain of function” (GOF) influenza virus research, or simply GOF. As will be seen, there is nothing good to be gained. The controversial experiments confer aerosol transmission on avian influenza virus strains that can infect humans, but which are not naturally transmitted between humans. Some of the newer strains are clearly highly path...

  17. Ecology, Evolution and Pathogenesis of Avian Influenza Viruses

    Munster, Vincent

    2006-01-01

    textabstractInfluenza A virus behoort tot de familie van Orthomyxoviridae. Infl uenza A virussen zijn onregelmatig gevormde virussen van ongeveer 120 nm groot. Het genoom van influenza A virussen is gesegmenteerd en bestaat uit negatief-strengs RNA. De acht gensegmenten coderen voor 11 verschillende eiwitten. Infl uenza A virussen worden onderverdeeld op basis van de oppervlakte eiwitten; hemagglutinine (HA, een eiwit dat zorg draagt voor de binding van het virus aan en binnendringen van de g...

  18. Detecting emerging transmissibility of avian influenza virus in human households

    van Boven, M.; Koopmans, M.; Du Ry van Beest Holle, M.; Meijer, Adam; Klinkenberg, D.; Donnelly, C. A.; Heesterbeek, J A P

    2007-01-01

    Accumulating infections of highly pathogenic H5N1 avian influenza in humans underlines the need to track the ability of these viruses to spread among humans. A human-transmissible avian influenza virus is expected to cause clusters of infections in humans living in close contact. Therefore, epidemiological analysis of infection clusters in human households is of key importance. Infection clusters may arise from transmission events from (i) the animal reservoir, (ii) humans who were infected b...

  19. Pandemic swine influenza virus (H1N1): A threatening evolution.

    Khanna, Madhu; Kumar, Binod; Gupta, Neha; Kumar, Prashant; Gupta, Ankit; Vijayan, V K; Kaur, Harpreet

    2009-12-01

    "Survival of the fittest" is an old axiom laid down by the great evolutionist Charles Darwin and microorganisms seem to have exploited this statement to a great extent. The ability of viruses to adapt themselves to the changing environment has made it possible to inhabit itself in this vast world for the past millions of years. Experts are well versed with the fact that influenza viruses have the capability to trade genetic components from one to the other within animal and human population. In mid April 2009, the Centers for Disease Control and Prevention and the World Health Organization had recognized a dramatic increase in number of influenza cases. These current 2009 infections were found to be caused by a new strain of influenza type A H1N1 virus which is a re-assortment of several strains of influenza viruses commonly infecting human, avian, and swine population. This evolution is quite dependent on swine population which acts as a main reservoir for the reassortment event in virus. With the current rate of progress and the efforts of heath authorities worldwide, we have still not lost the race against fighting this virus. This article gives an insight to the probable source of origin and the evolutionary progress it has gone through that makes it a potential threat in the future, the current scenario and the possible measures that may be explored to further strengthen the war against pandemic. PMID:23100799

  20. Single mutation at the amino acid position 627 of PB2 that leads to increased virulence of an H5N1 avian influenza virus during adaptation in mice can be compensated by multiple mutations at other sites of PB2.

    Li, Junwei; Ishaq, Musarat; Prudence, Mabiala; Xi, Xiao; Hu, Tao; Liu, Qingzhen; Guo, Deyin

    2009-09-01

    To understand the adaptation of H5N1 influenza viruses to mammals, a non-pathogenic influenza H5N1 virus (HN021) in mice was passaged for 15 times in mammalian host. Animal experimental results indicated that the mouse-adapted (MA) variants became highly pathogenic in mice after the passages. Sequence analysis showed that there was one amino acid substitution in PB2 protein of MA mutants after first passage (MA1), three amino acid substitutions in PB2 protein of MA5 and one amino acid in M1 protein, seven amino acids in HA protein and seven amino acids in PB2 protein of MA15, respectively. Animal experiments and growth assays with reassortant viruses produced by reverse genetics showed that mutations in PB2 alone contributed to the increase in virulence of HN021 in mice. Polymerase activity assays showed that the mutations in PB2 enhanced ribonucleoprotein complex polymerase activity in mammalian cells. Interestingly, one reverse mutation (K627E) took place at the amino acid position 627 of PB2 during passages of MA5 to MA15, indicating that a lysine at position 627 of PB2 is not absolutely needed for virulence and adaptation in mice by H5N1 virus. Taken together, the results suggest that mutations at multiple sites of PB2 contributed to the virulence and adaptation in mice, and the E627K mutation of PB2 is not an indispensable determinant in PB2 for mammalian adaptation by H5N1 avian influenza virus. PMID:19393699

  1. Antiviral Activities of Several Oral Traditional Chinese Medicines against Influenza Viruses

    Lin-Lin Ma; Miao Ge; Hui-Qiang Wang; Jin-Qiu Yin; Jian-Dong Jiang; Yu-Huan Li

    2015-01-01

    Influenza is still a serious threat to human health with significant morbidity and mortality. The emergence of drug-resistant influenza viruses poses a great challenge to existing antiviral drugs. Traditional Chinese medicines (TCMs) may be an alternative to overcome the challenge. Here, 10 oral proprietary Chinese medicines were selected to evaluate their anti-influenza activities. These drugs exhibit potent inhibitory effects against influenza A H1N1, influenza A H3N2, and influenza B virus...

  2. Avian influenza virus risk assessment in falconry

    Lüschow Dörte

    2011-04-01

    Full Text Available Abstract Background There is a continuing threat of human infections with avian influenza viruses (AIV. In this regard falconers might be a potential risk group because they have close contact to their hunting birds (raptors such as falcons and hawks as well as their avian prey such as gulls and ducks. Both (hunting birds and prey birds seem to be highly susceptible to some AIV strains, especially H5N1. We therefore conducted a field study to investigate AIV infections in falconers, their falconry birds as well as prey birds. Findings During 2 hunting seasons (2006/2007 and 2007/2008 falconers took tracheal and cloacal swabs from 1080 prey birds that were captured by their falconry birds (n = 54 in Germany. AIV-RNA of subtypes H6, H9, or H13 was detected in swabs of 4.1% of gulls (n = 74 and 3.8% of ducks (n = 53 using RT-PCR. The remaining 953 sampled prey birds and all falconry birds were negative. Blood samples of the falconry birds tested negative for AIV specific antibodies. Serum samples from all 43 falconers reacted positive in influenza A virus-specific ELISA, but remained negative using microneutralisation test against subtypes H5 and H7 and haemagglutination inhibition test against subtypes H6, H9 and H13. Conclusion Although we were able to detect AIV-RNA in samples from prey birds, the corresponding falconry birds and falconers did not become infected. Currently falconers do not seem to carry a high risk for getting infected with AIV through handling their falconry birds and their prey.

  3. The Influenza NS1 Protein: What Do We Know in Equine Influenza Virus Pathogenesis?

    Barba, Marta; Daly, Janet M

    2016-01-01

    Equine influenza virus remains a serious health and potential economic problem throughout most parts of the world, despite intensive vaccination programs in some horse populations. The influenza non-structural protein 1 (NS1) has multiple functions involved in the regulation of several cellular and viral processes during influenza infection. We review the strategies that NS1 uses to facilitate virus replication and inhibit antiviral responses in the host, including sequestering of double-stranded RNA, direct modulation of protein kinase R activity and inhibition of transcription and translation of host antiviral response genes such as type I interferon. Details are provided regarding what it is known about NS1 in equine influenza, especially concerning C-terminal truncation. Further research is needed to determine the role of NS1 in equine influenza infection, which will help to understand the pathophysiology of complicated cases related to cytokine imbalance and secondary bacterial infection, and to investigate new therapeutic and vaccination strategies. PMID:27589809

  4. Avian Influenza Virus Glycoproteins Restrict Virus Replication and Spread through Human Airway Epithelium at Temperatures of the Proximal Airways

    Scull, Margaret A.; Gillim-Ross, Laura; Santos, Celia; Roberts, Kim L.; Bordonali, Elena; Subbarao, Kanta; Barclay, Wendy S.; Pickles, Raymond J.

    2009-01-01

    Transmission of avian influenza viruses from bird to human is a rare event even though avian influenza viruses infect the ciliated epithelium of human airways in vitro and ex vivo. Using an in vitro model of human ciliated airway epithelium (HAE), we demonstrate that while human and avian influenza viruses efficiently infect at temperatures of the human distal airways (37°C), avian, but not human, influenza viruses are restricted for infection at the cooler temperatures of the human proximal ...

  5. Developments of Subunit and VLP Vaccines Against Influenza A Virus

    Ma-ping Deng; Zhi-hong Hu; Hua-lin Wang; Fei Deng

    2012-01-01

    Influenza virus is a continuous and severe global threat to mankind.The continuously re-emerging disease gives rise to thousands of deaths and enormous economic losses each year,which emphasizes the urgency and necessity to develop high-quality influenza vaccines in a safer,more efficient and economic way.The influenza subunit and VLP vaccines,taking the advantage of recombinant DNA technologies and expression system platforms,can be produced in such an ideal way.This review summarized the recent advancements in the research and development of influenza subunit and VLP vaccines based on the recombinant expression of hemagglutinin antigen (HA),neuraminidase antigen (NA),Matrix 2 protein (M2) and nucleocapsid protein (NP).It would help to get insight into the current stage of influenza vaccines,and suggest the future design and development of novel influenza vaccines.

  6. Neuraminidase Resistant Sialosides for the Detection of Influenza Viruses.

    He, Yun; Yang, Yang; Iyer, Suri S

    2016-06-15

    We report the synthesis of influenza virus neuraminidase (NA) resistant sialosides that include different glycoside linkages (C-, S-, and triazole). These unnatural sialosides were printed onto glass slides to generate a small focused microarray. We evaluated the binding affinity of multiple lectins and compared the stability of these sialosides with O-linked sialosides toward influenza virus neuraminidase and intact virus. We demonstrated the ability of these molecules to capture eight different strains of influenza virus at ambient temperature without the addition of NA inhibitors. The glycans capture extremely low, clinically relevant concentrations of viruses and each strain gives rise to a specific "fingerprint" binding pattern, which could potentially be used in rapid diagnostic tests. PMID:27139196

  7. A20 Deficiency in Lung Epithelial Cells Protects against Influenza A Virus Infection

    Vereecke, Lars; Mc Guire, Conor; Sze, Mozes; Schuijs, Martijn J.; Willart, Monique; Itati Ibañez, Lorena; Hammad, Hamida; Lambrecht, Bart N.; Beyaert, Rudi; Saelens, Xavier; van Loo, Geert

    2016-01-01

    A20 negatively regulates multiple inflammatory signalling pathways. We here addressed the role of A20 in club cells (also known as Clara cells) of the bronchial epithelium in their response to influenza A virus infection. Club cells provide a niche for influenza virus replication, but little is known about the functions of these cells in antiviral immunity. Using airway epithelial cell-specific A20 knockout (A20AEC-KO) mice, we show that A20 in club cells critically controls innate immune responses upon TNF or double stranded RNA stimulation. Surprisingly, A20AEC-KO mice are better protected against influenza A virus challenge than their wild type littermates. This phenotype is not due to decreased viral replication. Instead host innate and adaptive immune responses and lung damage are reduced in A20AEC-KO mice. These attenuated responses correlate with a dampened cytotoxic T cell (CTL) response at later stages during infection, indicating that A20AEC-KO mice are better equipped to tolerate Influenza A virus infection. Expression of the chemokine CCL2 (also named MCP-1) is particularly suppressed in the lungs of A20AEC-KO mice during later stages of infection. When A20AEC-KO mice were treated with recombinant CCL2 the protective effect was abrogated demonstrating the crucial contribution of this chemokine to the protection of A20AEC-KO mice to Influenza A virus infection. Taken together, we propose a mechanism of action by which A20 expression in club cells controls inflammation and antiviral CTL responses in response to influenza virus infection. PMID:26815999

  8. The global antigenic diversity of swine influenza A viruses

    Lewis, Nicola S; Russell, Colin A; Langat, Pinky; Anderson, Tavis K; Berger, Kathryn; Bielejec, Filip; Burke, David F; Dudas, Gytis; Fonville, Judith M; Fouchier, Ron AM; Kellam, Paul; Koel, Bjorn F; Lemey, Philippe; Nguyen, Tung; Nuansrichy, Bundit; Peiris, JS Malik; Saito, Takehiko; Simon, Gaelle; Skepner, Eugene; Takemae, Nobuhiro; Webby, Richard J; Van Reeth, Kristien; Brookes, Sharon M; Larsen, Lars; Watson, Simon J; Brown, Ian H; Vincent, Amy L

    2016-01-01

    Swine influenza presents a substantial disease burden for pig populations worldwide and poses a potential pandemic threat to humans. There is considerable diversity in both H1 and H3 influenza viruses circulating in swine due to the frequent introductions of viruses from humans and birds coupled with geographic segregation of global swine populations. Much of this diversity is characterized genetically but the antigenic diversity of these viruses is poorly understood. Critically, the antigenic diversity shapes the risk profile of swine influenza viruses in terms of their epizootic and pandemic potential. Here, using the most comprehensive set of swine influenza virus antigenic data compiled to date, we quantify the antigenic diversity of swine influenza viruses on a multi-continental scale. The substantial antigenic diversity of recently circulating viruses in different parts of the world adds complexity to the risk profiles for the movement of swine and the potential for swine-derived infections in humans. DOI: http://dx.doi.org/10.7554/eLife.12217.001 PMID:27113719

  9. The fast diagnosis by different methodologies of the influenza virus

    Iris Hatibi

    2013-09-01

    Full Text Available This paper presents the causative agent of the epidemic of the influenza in our country during the season 2009-2010. It also shows the effectiveness of the molecular diagnosis for Influenza virus by the means of the real-time PCR method in comparative of classical virological ones. Also in this paper we have presented the antigenic characterization of this virus which caused the pandemic during 2009-2010 years. We have collected and processed with several diagnostic methods like imunoflorescent assay, rapid tests, isolation and molecular method 409 samples. These were collected by the means of a Sentinel Surveillance throughout Albania, (tampon nasal- pharyngeal from people suspected of influenza in different ages. To isolate the virus of influenza we have used two methods: the method of isolation of influenza in the cell line of MDCK and also the isolation of the viral RNA by the means of the molecular method. The identifications of the isolates were carried out through the reactions of the hem agglutination inhibition and we have used also the method of Immunofluorescence and rapid test for the antigen detection of influenza virus. The results of the virus analyses are given in the relevant figures. The positive isolates were sent to the International Center of Influenza in London to be confirmed and also to have a further genetic analysis through molecular methods. From these tests performed during the season 2009-2010, it came out that our country was affected by one strain of influenza type A, AH1N1 variant A/California/2009/11. This strain circulated in the whole world causing the pandemic of 2009 and was a new variant deriving from the fusion of 4 strains of Influenza a process which occurred in pigs. These variants have affected the majority of the countries in Europe and in the world.

  10. Oseltamivir (Tamiflu® in the environment, resistance development in influenza A viruses of dabbling ducks and the risk of transmission of an oseltamivir-resistant virus to humans – a review

    Josef D. Järhult

    2012-06-01

    Full Text Available The antiviral drug oseltamivir (Tamiflu® is a cornerstone in influenza pandemic preparedness plans worldwide. However, resistance to the drug is a growing concern. The active metabolite oseltamivir carboxylate (OC is not degraded in surface water or sewage treatment plants and has been detected in river water during seasonal influenza outbreaks. The natural influenza reservoir, dabbling ducks, can thus be exposed to OC in aquatic environments. Environmental-like levels of OC induce resistance development in influenza A/H1N1 virus in mallards. There is a risk of resistance accumulation in influenza viruses circulating among wild birds when oseltamivir is used extensively. By reassortment or direct transmission, oseltamivir resistance can be transmitted to humans potentially causing a resistant pandemic or human-adapted highly-pathogenic avian influenza virus. There is a need for more research on resistance development in the natural influenza reservoir and for a prudent use of antivirals.

  11. El virus influenza y la gripe aviar Influenza virus and avian flu

    Libia Herrero-Uribe

    2008-01-01

    En este artículo se presenta una revisión del virus influenza,su biología,sus mecanismos de variación antigénica,las pandemias que ha producido y la prevención mediante las vacunas y medicamentos antivirales.Se analizan las razones por las cuales aparece el virus H5N1 que produce la fiebre aviar en humanos,la patogénesis de este virus y las estrategias para su prevención.Se informa sobre el plan de preparación para la pandemia en los niveles nacional e internacional.This article presents a re...

  12. Highly pathogenic avian influenza viruses inhibit effective immune responses of human blood-derived macrophages

    Friesenhagen, Judith; Boergeling, Yvonne; Hrincius, Eike; Ludwig, Stephan; Roth, Johannes; Viemann, Dorothee

    2012-01-01

    Human blood-derived macrophages are non-permissive for influenza virus propagation, and fail to elicit inflammatory and antiviral responses upon infection with high pathogenic avian influenza viruses.

  13. Compounds with anti-influenza activity: present and future of strategies for the optimal treatment and management of influenza Part II: Future compounds against influenza virus

    Gasparini, R; Amicizia, D.; Lai, P. L.; BRAGAZZI, N.L.; PANATTO, D.

    2014-01-01

    Summary In the first part of this overview, we described the life cycle of the influenza virus and the pharmacological action of the currently available drugs. This second part provides an overview of the molecular mechanisms and targets of still-experimental drugs for the treatment and management of influenza. Briefly, we can distinguish between compounds with anti-influenza activity that target influenza virus proteins or genes, and molecules that target host components that are essential f...

  14. Selecting Viruses for the Seasonal Influenza Vaccine

    ... Japan (National Institute for Infectious Diseases); and Beijing, China (National Institute for Viral Disease Control and Prevention). ... Influenza (Flu) Vaccines Are Made . Top of Page Influenza Types Seasonal Avian Swine Variant Pandemic Other Get Email Updates To ...

  15. Panorama phylogenetic diversity and distribution of Type A influenza virus.

    Shuo Liu

    Full Text Available BACKGROUND: Type A influenza virus is one of important pathogens of various animals, including humans, pigs, horses, marine mammals and birds. Currently, the viral type has been classified into 16 hemagglutinin and 9 neuraminidase subtypes, but the phylogenetic diversity and distribution within the viral type largely remain unclear from the whole view. METHODOLOGY/PRINCIPAL FINDINGS: The panorama phylogenetic trees of influenza A viruses were calculated with representative sequences selected from approximately 23,000 candidates available in GenBank using web servers in NCBI and the software MEGA 4.0. Lineages and sublineages were classified according to genetic distances, topology of the phylogenetic trees and distributions of the viruses in hosts, regions and time. CONCLUSIONS/SIGNIFICANCE: Here, two panorama phylogenetic trees of type A influenza virus covering all the 16 hemagglutinin subtypes and 9 neuraminidase subtypes, respectively, were generated. The trees provided us whole views and some novel information to recognize influenza A viruses including that some subtypes of avian influenza viruses are more complicated than Eurasian and North American lineages as we thought in the past. They also provide us a framework to generalize the history and explore the future of the viral circulation and evolution in different kinds of hosts. In addition, a simple and comprehensive nomenclature system for the dozens of lineages and sublineages identified within the viral type was proposed, which if universally accepted, will facilitate communications on the viral evolution, ecology and epidemiology.

  16. Seroepidemiological Evidence of Avian Influenza A Virus Transmission to Pigs in Southern China

    Su, Shuo; Qi, Wenbao; Chen, Jidang; Zhu, Wanjun; Huang, Zhen; Xie, Jiexiong; Zhang, Guihong

    2013-01-01

    Recently, three novel avian-origin swine influenza viruses (SIVs) were first isolated from pigs in Guangdong Province, southern China, yet little is known about the seroprevalence of avian influenza viruses among pigs in southern China. Here, we report for the first time the seroprevalence of avian H3, H4, and H6 influenza viruses in swine populations and the lack of seroepidemiological evidence of avian H5 influenza virus transmission to pigs in China.

  17. Reverse Genetics Plasmid for Cloning Unstable Influenza A Virus Gene Segments

    Zhou, Bin; Jerzak, Greta; Scholes, Derek T.; Donnelly, Matthew E.; Li, Yan; Wentworth, David E.

    2011-01-01

    Reverse genetics approaches that enable the generation of recombinant influenza A viruses entirely from plasmids are invaluable for studies on virus replication, morphogenesis, pathogenesis, or transmission. Furthermore, influenza virus reverse genetics is now critical for the development of new vaccines for this human and animal pathogen. Periodically, influenza gene segments are unstable within plasmids in bacteria. The PB2 gene segment of a highly pathogenic avian H5 influenza virus A/Turk...

  18. Protection against divergent influenza H1N1 virus by a centralized influenza hemagglutinin.

    Weaver, Eric A; Rubrum, Adam M; Webby, Richard J; Barry, Michael A

    2011-01-01

    Influenza poses a persistent worldwide threat to the human population. As evidenced by the 2009 H1N1 pandemic, current vaccine technologies are unable to respond rapidly to this constantly diverging pathogen. We tested the utility of adenovirus (Ad) vaccines expressing centralized consensus influenza antigens. Ad vaccines were produced within 2 months and protected against influenza in mice within 3 days of vaccination. Ad vaccines were able to protect at doses as low as 10(7) virus particles/kg indicating that approximately 1,000 human doses could be rapidly generated from standard Ad preparations. To generate broadly cross-reactive immune responses, centralized consensus antigens were constructed against H1 influenza and against H1 through H5 influenza. Twenty full-length H1 HA sequences representing the main branches of the H1 HA phylogenetic tree were used to create a synthetic centralized gene, HA1-con. HA1-con minimizes the degree of sequence dissimilarity between the vaccine and existing circulating viruses. The centralized H1 gene, HA1-con, induced stronger immune responses and better protection against mismatched virus challenges as compared to two wildtype H1 genes. HA1-con protected against three genetically diverse lethal influenza challenges. When mice were challenged with 1934 influenza A/PR/8/34, HA1-con protected 100% of mice while vaccine generated from 2009 A/TX/05/09 only protected 40%. Vaccination with 1934 A/PR/8/34 and 2009 A/TX/05/09 protected 60% and 20% against 1947 influenza A/FM/1/47, respectively, whereas 80% of mice vaccinated with HA1-con were protected. Notably, 80% of mice challenged with 2009 swine flu isolate A/California/4/09 were protected by HA1-con vaccination. These data show that HA1-con in Ad has potential as a rapid and universal vaccine for H1N1 influenza viruses. PMID:21464940

  19. Control of Influenza and Poliomyelitis with Killed Virus Vaccines

    Salk, Jonas; Salk, Darrell

    1977-01-01

    Discusses control of poliomyelitis and influenza by live and killed virus vaccines. Considered are the etiological agents, pathogenic mechanisms and epidemiology of each disease. Reviews recent scientific studies of the diseases. Recommends use of killed virus vaccines in controlling both diseases. (CS)

  20. Quantitative Risk Assessment of Avian Influenza Virus Infection via Water

    Schijven FJ; Teunis PFM; Roda Husman AM de; MGB

    2006-01-01

    Using literature data, daily infection risks of chickens and humans with H5N1 avian influenza virus (AIV) by drinking water consumption were estimated for the Netherlands. A highly infectious virus and less than 4 log10 drinking water treatment (reasonably inefficient) may lead to a high infection r

  1. DETECTION OF AVIAN INFLUENZA VIRUS USING AN INTERFEROMETRIC BIOSENSOR

    An optical interferometric waveguide immunoassay for direct and label-less detection of avian influenza virus is described. The assay response is based on index of refraction changes that occur upon binding of virus particles to antigen (hemagglutinin) specific antibodies on the waveguide surface. ...

  2. A new model for simulating evolution of human influenza virus

    2008-01-01

    @@ Understanding the evolution of influenza A virus, which poses a global challenge to public health, is of special significance for its control and prevention. Although the genome structure of the virus is seemingly simple, their evolutionary patterns and molecular mechanisms are difficult to reveal.

  3. Immunohistochemical staining of avian influenza virus in tissues

    Immunohistochemical methods are commonly used for studying the pathogenesis of avian influenza (AI) virus by allowing the identification of sites of replication of the virus in infected tissues and the correlation with the histopathological changes observed. In this chapter, the materials and metho...

  4. Influenza Virus Surveillance in Coordinated Swine Production Systems, United States.

    Kaplan, Bryan S; DeBeauchamp, Jennifer; Stigger-Rosser, Evelyn; Franks, John; Crumpton, Jeri Carol; Turner, Jasmine; Darnell, Daniel; Jeevan, Trushar; Kayali, Ghazi; Harding, Abbey; Webby, Richard J; Lowe, James F

    2015-10-01

    To clarify the epidemiology of influenza A viruses in coordinated swine production systems to which no animals from outside the system are introduced, we conducted virologic surveillance during September 2012-September 2013. Animal age, geographic location, and farm type were found to affect the prevalence of these viruses. PMID:26402228

  5. Influenza and other respiratory viruses in three Central American countries

    Laguna‐Torres, Victor A.; Sánchez‐Largaespada, José F.; Lorenzana, Ivette; Forshey, Brett; Aguilar, Patricia; Jimenez, Mirna; Parrales, Eduardo; Rodriguez, Francisco; García, Josefina; Jimenez, Ileana; Rivera, Maribel; Perez, Juan; Sovero, Merly; Rios, Jane; Gamero, María E.; Halsey, Eric S.; Kochel, Tadeusz J.

    2010-01-01

    Please cite this paper as: Laguna‐Torres et al. (2011) Influenza and other respiratory viruses in three Central American countries. Influenza and Other Respiratory Viruses 5(2), 123–134. Background  Despite the disease burden imposed by respiratory diseases on children in Central America, there is a paucity of data describing the etiologic agents of the disease. Aims  To analyze viral etiologic agents associated with influenza‐like illness (ILI) in participants reporting to one outpatient health center, one pediatric hospital, and three general hospitals in El Salvador, Honduras, and Nicaragua Material & Methods  Between August 2006 and April 2009, pharyngeal swabs were collected from outpatients and inpatients. Patient specimens were inoculated onto cultured cell monolayers, and viral antigens were detected by indirect and direct immunofluorescence staining. Results  A total of 1,756 patients were enrolled, of whom 1,195 (68.3%) were under the age of 5; and 183 (10.4%) required hospitalization. One or more viral agents were identified in 434 (24.7%) cases, of which 17 (3.9%) were dual infections. The most common viruses isolated were influenza A virus (130; 7.4% of cases), respiratory syncytial virus (122; 6.9%), adenoviruses (63; 3.6%), parainfluenza viruses (57; 3.2%), influenza B virus (47; 2.7% of cases), and herpes simplex virus 1 (22; 1.3%). In addition, human metapneumovirus and enteroviruses (coxsackie and echovirus) were isolated from patient specimens. Discussion  When compared to the rest of the population, viruses were isolated from a significantly higher percentage of patients age 5 or younger. The prevalence of influenza A virus or influenza B virus infections was similar between the younger and older age groups. RSV was the most commonly detected pathogen in infants age 5 and younger and was significantly associated with pneumonia (p < 0.0001) and hospitalization (p < 0.0001). Conclusion  Genetic analysis of influenza

  6. Swine Influenza Viruses: a North American Perspective

    Influenza is a zoonotic viral disease that represents a health and economic threat to both humans and animals worldwide. Swine influenza was first recognized clinically in pigs in the Midwestern U.S. in 1918, coinciding with the human influenza pandemic known as the Spanish flu. Since that time swin...

  7. Within-host variation of avian influenza viruses

    Iqbal, Munir; Xiao, Hiaxia; Baillie, Greg; Warry, Andrew; Essen, Steve C.; Londt, Brandon; Brookes, Sharon M; Brown, Ian H.; McCauley, John W.

    2009-01-01

    The emergence and spread of H5N1 avian influenza viruses from Asia through to Europe and Africa pose a significant animal disease problem and have raised concerns that the virus may pose a pandemic threat to humans. The epizootological factors that have influenced the wide distribution of the virus are complex, and the variety of viruses currently circulating reflects these factors. Sequence analysis of the virus genes sheds light on the H5N1 virus evolution during its emergence and spread, b...

  8. Antibody Recognition of a Highly Conserved Influenza Virus Epitope

    Ekiert, Damian C.; Bhabha, Gira; Elsliger, Marc-André; Friesen, Robert H.E.; Jongeneelen, Mandy; Throsby, Mark; Goudsmit, Jaap; Wilson, Ian A.; Scripps; Crucell

    2009-05-21

    Influenza virus presents an important and persistent threat to public health worldwide, and current vaccines provide immunity to viral isolates similar to the vaccine strain. High-affinity antibodies against a conserved epitope could provide immunity to the diverse influenza subtypes and protection against future pandemic viruses. Cocrystal structures were determined at 2.2 and 2.7 angstrom resolutions for broadly neutralizing human antibody CR6261 Fab in complexes with the major surface antigen (hemagglutinin, HA) from viruses responsible for the 1918 H1N1 influenza pandemic and a recent lethal case of H5N1 avian influenza. In contrast to other structurally characterized influenza antibodies, CR6261 recognizes a highly conserved helical region in the membrane-proximal stem of HA1 and HA2. The antibody neutralizes the virus by blocking conformational rearrangements associated with membrane fusion. The CR6261 epitope identified here should accelerate the design and implementation of improved vaccines that can elicit CR6261-like antibodies, as well as antibody-based therapies for the treatment of influenza.

  9. Cloned defective interfering influenza virus protects ferrets from pandemic 2009 influenza A virus and allows protective immunity to be established.

    Nigel J Dimmock

    Full Text Available Influenza A viruses are a major cause of morbidity and mortality in the human population, causing epidemics in the winter, and occasional worldwide pandemics. In addition there are periodic outbreaks in domestic poultry, horses, pigs, dogs, and cats. Infections of domestic birds can be fatal for the birds and their human contacts. Control in man operates through vaccines and antivirals, but both have their limitations. In the search for an alternative treatment we have focussed on defective interfering (DI influenza A virus. Such a DI virus is superficially indistinguishable from a normal virus but has a large deletion in one of the eight RNAs that make up the viral genome. Antiviral activity resides in the deleted RNA. We have cloned one such highly active DI RNA derived from segment 1 (244 DI virus and shown earlier that intranasal administration protects mice from lethal disease caused by a number of different influenza A viruses. A more cogent model of human influenza is the ferret. Here we found that intranasal treatment with a single dose of 2 or 0.2 µg 244 RNA delivered as A/PR/8/34 virus particles protected ferrets from disease caused by pandemic virus A/California/04/09 (A/Cal; H1N1. Specifically, 244 DI virus significantly reduced fever, weight loss, respiratory symptoms, and infectious load. 244 DI RNA, the active principle, was amplified in nasal washes following infection with A/Cal, consistent with its amelioration of clinical disease. Animals that were treated with 244 DI RNA cleared infectious and DI viruses without delay. Despite the attenuation of infection and disease by DI virus, ferrets formed high levels of A/Cal-specific serum haemagglutination-inhibiting antibodies and were solidly immune to rechallenge with A/Cal. Together with earlier data from mouse studies, we conclude that 244 DI virus is a highly effective antiviral with activity potentially against all influenza A subtypes.

  10. Influenza A virus infection in zebrafish recapitulates mammalian infection and sensitivity to anti-influenza drug treatment

    Gabor, Kristin A.; Michelle F. Goody; Mowel, Walter K; Breitbach, Meghan E.; Gratacap, Remi L.; P. Eckhard Witten; Kim, Carol H.

    2014-01-01

    Seasonal influenza virus infections cause annual epidemics and sporadic pandemics. These present a global health concern, resulting in substantial morbidity, mortality and economic burdens. Prevention and treatment of influenza illness is difficult due to the high mutation rate of the virus, the emergence of new virus strains and increasing antiviral resistance. Animal models of influenza infection are crucial to our gaining a better understanding of the pathogenesis of and host response to i...

  11. Contemporary North American influenza H7 viruses possess human receptor specificity: Implications for virus transmissibility

    Belser, Jessica A; Blixt, Ola; Chen, Li-Mei; Pappas, Claudia; Maines, Taronna R; Van Hoeven, Neal; Donis, Ruben; Busch, Julia; McBride, Ryan; Paulson, James C; Katz, Jacqueline M; Tumpey, Terrence M

    2008-01-01

    viruses from The Netherlands in 2003 maintained the classic avian-binding preference for alpha2-3-linked sialic acids (SA) and are not readily transmissible in ferrets, as observed previously for highly pathogenic H5N1 viruses. However, H7N3 viruses isolated from Canada in 2004 and H7N2 viruses from the...... in the upper respiratory tract of ferrets and was capable of transmission in this species by direct contact. These results indicate that H7 influenza viruses from the North American lineage have acquired sialic acid-binding properties that more closely resemble those of human influenza viruses and...

  12. Chiropteran influenza viruses: flu from bats or a relic from the past?

    Brunotte, Linda; Beer, Martin; Horie, Masayuki; Schwemmle, Martin

    2016-02-01

    The identification of influenza A-like genomic sequences in bats suggests the existence of distinct lineages of chiropteran influenza viruses in South and Central America. These viruses share similarities with conventional influenza A viruses but lack the canonical receptor-binding property and neuraminidase function. The inability to isolate infectious bat influenza viruses impeded further studies, however, reverse genetic analysis provided new insights into the molecular biology of these viruses. In this review, we highlight the recent developments in the field of the newly discovered bat-derived influenza A-like viruses. We also discuss whether bats are a neglected natural reservoir of influenza viruses, the risk associated with bat influenza viruses for humans and whether these viruses originate from the pool of avian IAV or vice versa. PMID:26947779

  13. Novel Reassortant Highly Pathogenic Avian Influenza (H5N5) Viruses in Domestic Ducks, China

    Gu, Min; Liu, Wenbo; Cao, Yongzhong; Peng, Daxin; Wang, Xiaobo; Wan, Hongquan; Zhao, Guo; Xu, Quangang; Zhang, Wei; Song, Qingqing; Li, Yanfang; Liu, Xiufan

    2011-01-01

    In China, domestic ducks and wild birds often share the same water, in which influenza viruses replicate preferentially. Isolation of 2 novel reassortant highly pathogenic avian influenza (H5N5) viruses from apparently healthy domestic ducks highlights the role of these ducks as reassortment vessels. Such new subtypes of influenza viruses may pose a pandemic threat.

  14. Lack of chicken adaptation of newly emergent Eurasian H5N8 and reassortant H5N2 high pathogenicity avian influenza viruses in the U.S. is consistent with restricted poultry outbreaks in the Pacific flyway during 2014-2015.

    Bertran, Kateri; Swayne, David E; Pantin-Jackwood, Mary J; Kapczynski, Darrell R; Spackman, Erica; Suarez, David L

    2016-07-01

    In 2014-2015, the U.S. experienced an unprecedented outbreak of Eurasian clade 2.3.4.4 H5 highly pathogenic avian influenza (HPAI) virus, initially affecting mainly wild birds and few backyard and commercial poultry premises. To better model the outbreak, the pathogenesis and transmission dynamics of representative Eurasian H5N8 and reassortant H5N2 clade 2.3.4.4 HPAI viruses detected early in the North American outbreak were investigated in chickens. High mean chicken infectious doses and lack of seroconversion in survivors indicated the viruses were poorly chicken adapted. Pathobiological features were consistent with HPAI virus infection, although the delayed appearance of lesions, longer mean death times, and reduced replication in endothelial cells differed from features of most other Eurasian H5N1 HPAI viruses. Although these initial U.S. H5 HPAI viruses had reduced adaptation and transmissibility in chickens, multi-generational passage in poultry could generate poultry adapted viruses with higher infectivity and transmissibility. PMID:27110710

  15. Efficacy of Inactivated Swine Influenza Virus Vaccines Against 2009 H1N1 Influenza Virus in Pigs

    Introduction. The gene constellation of the 2009 pandemic H1N1 virus is a unique combination from swine influenza A viruses (SIV) of North American and Eurasian lineages, but prior to April 2009 had never before been identified in swine or other species (1). Although its hemagglutinin gene is relat...

  16. Apoptosis in Raji cell line induced by influenza A virus

    李虹; 肖丽英; 李华林; 李婉宜; 蒋中华; 张林; 李明远

    2003-01-01

    Objective To study the apoptotic effects of influenza A virus on the Raji cell line. Methods Cultured Raji cells were infected with influenza A virus at a multiplicity of infection (m.o.i) of 20 and the effects of apoptosis were detected at different time points post infection using the following methods: electron microscope, DNA agarose gel electrophoresis, PI stained flow cytometry (FCM) and Annexin-V FITC/PI stained FCM.Results Raji cells infected with influenza A virus showed changes of morphology apoptotis, DNA agarose electrophoresis also demonstrated a ladder-like pattern of DNA fragments in a time-dependent manner. PI stained FCM showed "apoptosis peak" and FITC/PI stained FCM showed apoptotic cells. Quantitative analysis indicated that the percentage of apoptotic Raji cells increased after infection, and cycloheximide (CHX), an eukaryotic transcription inhibitor, could effectively inhibit the apoptotic effects of influenza A virus in vitro.Conclusions Influenza A virus can induce apoptosis in Raji cell line suggesting that it may lead to a potential method for tumor therapy.

  17. Detecting emerging transmissibility of avian influenza virus in human households.

    Michiel van Boven

    2007-07-01

    Full Text Available Accumulating infections of highly pathogenic H5N1 avian influenza in humans underlines the need to track the ability of these viruses to spread among humans. A human-transmissible avian influenza virus is expected to cause clusters of infections in humans living in close contact. Therefore, epidemiological analysis of infection clusters in human households is of key importance. Infection clusters may arise from transmission events from (i the animal reservoir, (ii humans who were infected by animals (primary human-to-human transmission, or (iii humans who were infected by humans (secondary human-to-human transmission. Here we propose a method of analysing household infection data to detect changes in the transmissibility of avian influenza viruses in humans at an early stage. The method is applied to an outbreak of H7N7 avian influenza virus in The Netherlands that was the cause of more than 30 human-to-human transmission events. The analyses indicate that secondary human-to-human transmission is plausible for the Dutch household infection data. Based on the estimates of the within-household transmission parameters, we evaluate the effectiveness of antiviral prophylaxis, and conclude that it is unlikely that all household infections can be prevented with current antiviral drugs. We discuss the applicability of our method for the detection of emerging human-to-human transmission of avian influenza viruses in particular, and for the analysis of within-household infection data in general.

  18. Detailed Report on 2014/15 Influenza Virus Characteristics, and Estimates on Influenza Virus Vaccine Effectiveness from Austria’s Sentinel Physician Surveillance Network

    Redlberger-Fritz, Monika; Kundi, Michael; Popow-Kraupp, Theresia

    2016-01-01

    Background Influenza vaccine effectiveness (VE) is influenced by the antigenic similarity between vaccine- and circulating strains. Material and Methods This paper presents data obtained by the Austrian sentinel surveillance system on the evolution of influenza viruses during the season 2014/15 and its impact on influenza vaccine effectiveness in primary care in Austria as estimated by a test-negative case control design. VE estimates were performed for each influenza virus type/subtype, stra...

  19. Immunity to Pre-1950 H1N1 Influenza Viruses Confers Cross-Protection against the Pandemic Swine-Origin 2009 A (H1N1) Influenza Virus

    Skountzou, Ioanna; Koutsonanos, Dimitrios G.; Kim, Jin Hyang; Powers, Ryan; Satyabhama, Lakshmipriyadarshini; Masseoud, Feda; Weldon, William C.; Martin, Maria del Pilar; Mittler, Robert S.; Compans, Richard; Jacob, Joshy

    2010-01-01

    The 2009 H1N1 influenza virus outbreak is the first pandemic of the twenty-first century. Epidemiological data reveal that of all the people afflicted with H1N1 virus, 60 y old have pre-existing neutralizing Abs against the 2009 H1N1 virus. This finding suggests that influenza strains that circulated 50–60 y ago might provide cross-protection against the swine-origin 2009 H1N1 influenza virus. To test this, we determined the ability of representative H1N1 influenza viruses that circulated in ...

  20. Rapid Semiautomated Subtyping of Influenza Virus Species during the 2009 Swine Origin Influenza A H1N1 Virus Epidemic in Milwaukee, Wisconsin▿

    Bose, Michael E; Beck, Eric T.; Ledeboer, Nate; Kehl, Sue C.; Jurgens, Lisa A.; Patitucci, Teresa; Witt, Lorraine; LaGue, Elizabeth; Darga, Patrick; He, Jie; Fan, Jiang; Kumar, Swati; Kelly J. Henrickson

    2009-01-01

    In the spring of 2009, a novel influenza A (H1N1) virus (swine origin influenza virus [S-OIV]) emerged and began causing a large outbreak of illness in Milwaukee, WI. Our group at the Midwest Respiratory Virus Program laboratory developed a semiautomated real-time multiplex reverse transcription-PCR assay (Seasonal), employing the NucliSENS easyMAG system (bioMérieux, Durham, NC) and a Raider thermocycler (HandyLab Inc., Ann Arbor, MI), that typed influenza A virus, influenza B virus, and res...

  1. Evaluation of Jatropha curcas Linn. leaf extracts for its cytotoxicity and potential to inhibit hemagglutinin protein of influenza virus

    Patil, Deepak; Roy, Soumen; Dahake, Ritwik; Rajopadhye, Shreewardhan; Kothari, Sweta; Deshmukh, Ranjana; Chowdhary, Abhay

    2013-01-01

    Influenza is a serious respiratory illness which can be debilitating and cause complications that lead to hospitalization and death. Although influenza vaccine can prevent influenza virus infection, the only therapeutic options to treat influenza virus infection are antiviral agents. Given temporal and geographic changes and the shifts in antiviral drug resistance among influenza viruses, it is time to consider natural antiviral agents against influenza virus. Jatropha curcas is known for var...

  2. Requirements of New Vaccines against Novel Influenza Viruses

    Kobayashi, Osamu

    2014-01-01

    The currently available influenza vaccines were developed in the 1930s through the 1960s using technologies that were state-of-the art for the times. Decades of advancement in virology and immunology have provided the tools for making better vaccines against influenza virus. Among young children, live attenuated vaccine had significantly better efficacy than inactivated vaccine. An evaluation of the risks and benefits indicates that live attenuated vaccine should be a highly effective, safe v...

  3. Anti-influenza virus effect of aqueous extracts from dandelion

    He Wen; Han Huamin; Wang Wei; Gao Bin

    2011-01-01

    Abstract Background Human influenza is a seasonal disease associated with significant morbidity and mortality. Anti-flu Traditional Chinese Medicine (TCM) has played a significant role in fighting the virus pandemic. In TCM, dandelion is a commonly used ingredient in many therapeutic remedies, either alone or in conjunction with other natural substances. Evidence suggests that dandelion is associated with a variety of pharmacological activities. In this study, we evaluated anti-influenza viru...

  4. Rapid strategy for screening by pyrosequencing of influenza virus reassortants--candidates for live attenuated vaccines.

    Svetlana V Shcherbik

    Full Text Available BACKGROUND: Live attenuated influenza vaccine viruses (LAIVs can be generated by classical reassortment of gene segments between a cold adapted, temperature sensitive and attenuated Master Donor Virus (MDV and a seasonal wild-type (wt virus. The vaccine candidates contain hemagglutinin (HA and neuraminidase (NA genes derived from the circulating wt viruses and the remaining six genes derived from the MDV strains. Rapid, efficient selection of the viruses with 6∶2 genome compositions from the large number of genetically different viruses generated during reassortment is essential for the biannual production schedule of vaccine viruses. METHODOLOGY/PRINCIPAL FINDINGS: This manuscript describes a new approach for the genotypic analysis of LAIV reassortant virus clones based on pyrosequencing. LAIV candidate viruses were created by classical reassortment of seasonal influenza A (H3N2 (A/Victoria/361/2011, A/Ohio/02/2012, A/Texas/50/2012 or influenza A (H7N9 (A/Anhui/1/2013 wt viruses with the MDV A/Leningrad/134/17/57(H2N2. Using strain-specific pyrosequencing assays, mixed gene variations were detected in the allantoic progenies during the cloning procedure. The pyrosequencing analysis also allowed for estimation of the relative abundance of segment variants in mixed populations. This semi-quantitative approach was used for selecting specific clones for the subsequent cloning procedures. CONCLUSIONS/SIGNIFICANCE: The present study demonstrates that pyrosequencing analysis is a useful technique for rapid and reliable genotyping of reassortants and intermediate clones during the preparation of LAIV candidates, and can expedite the selection of vaccine virus candidates.

  5. Animal Models for Influenza Viruses: Implications for Universal Vaccine Development

    Irina Margine

    2014-10-01

    Full Text Available Influenza virus infections are a significant cause of morbidity and mortality in the human population. Depending on the virulence of the influenza virus strain, as well as the immunological status of the infected individual, the severity of the respiratory disease may range from sub-clinical or mild symptoms to severe pneumonia that can sometimes lead to death. Vaccines remain the primary public health measure in reducing the influenza burden. Though the first influenza vaccine preparation was licensed more than 60 years ago, current research efforts seek to develop novel vaccination strategies with improved immunogenicity, effectiveness, and breadth of protection. Animal models of influenza have been essential in facilitating studies aimed at understanding viral factors that affect pathogenesis and contribute to disease or transmission. Among others, mice, ferrets, pigs, and nonhuman primates have been used to study influenza virus infection in vivo, as well as to do pre-clinical testing of novel vaccine approaches. Here we discuss and compare the unique advantages and limitations of each model.

  6. Multi-antigen vaccines based on complex adenovirus vectors induce protective immune responses against H5N1 avian influenza viruses.

    Holman, David H; Wang, Danher; Raja, Nicholas U; Luo, Min; Moore, Kevin M; Woraratanadharm, Jan; Mytle, Nutan; Dong, John Y

    2008-05-19

    There are legitimate concerns that the highly pathogenic H5N1 avian influenza virus could adapt for human-to-human transmission and cause a pandemic similar to the 1918 "Spanish flu" that killed 50 million people worldwide. We have developed pandemic influenza vaccines by incorporating multiple antigens from both avian and Spanish influenza viruses into complex recombinant adenovirus vectors. In vaccinated mice, these vaccines induced strong humoral and cellular immune responses against pandemic influenza virus antigens, and protected vaccinated mice against lethal H5N1 virus challenge. These results indicate that this multi-antigen, broadly protective vaccine may serve as a safer and more effective approach than traditional methods for development of a pandemic influenza vaccine. PMID:18395306

  7. Complexities in Ferret Influenza Virus Pathogenesis and Transmission Models.

    Belser, Jessica A; Eckert, Alissa M; Tumpey, Terrence M; Maines, Taronna R

    2016-09-01

    Ferrets are widely employed to study the pathogenicity, transmissibility, and tropism of influenza viruses. However, inherent variations in inoculation methods, sampling schemes, and experimental designs are often overlooked when contextualizing or aggregating data between laboratories, leading to potential confusion or misinterpretation of results. Here, we provide a comprehensive overview of parameters to consider when planning an experiment using ferrets, collecting data from the experiment, and placing results in context with previously performed studies. This review offers information that is of particular importance for researchers in the field who rely on ferret data but do not perform the experiments themselves. Furthermore, this review highlights the breadth of experimental designs and techniques currently available to study influenza viruses in this model, underscoring the wide heterogeneity of protocols currently used for ferret studies while demonstrating the wealth of information which can benefit risk assessments of emerging influenza viruses. PMID:27412880

  8. Hsp90 inhibitors reduce influenza virus replication in cell culture

    The viral RNA polymerase complex of influenza A virus consists of three subunits PB1, PB2 and PA. Recently, the cellular chaperone Hsp90 was shown to play a role in nuclear import and assembly of the trimeric polymerase complex by binding to PB1 and PB2. Here we show that Hsp90 inhibitors, geldanamycin or its derivative 17-AAG, delay the growth of influenza virus in cell culture resulting in a 1-2 log reduction in viral titre early in infection. We suggest that this is caused by the reduced half-life of PB1 and PB2 and inhibition of nuclear import of PB1 and PA which lead to reduction in viral RNP assembly. Hsp90 inhibitors may represent a new class of antiviral compounds against influenza viruses

  9. Well-tolerated Spirulina extract inhibits influenza virus replication and reduces virus-induced mortality

    Yi-Hsiang Chen; Gi-Kung Chang; Shu-Ming Kuo; Sheng-Yu Huang; I-Chen Hu; Yu-Lun Lo; Shin-Ru Shih

    2016-01-01

    Influenza is one of the most common human respiratory diseases, and represents a serious public health concern. However, the high mutability of influenza viruses has hampered vaccine development, and resistant strains to existing anti-viral drugs have also emerged. Novel anti-influenza therapies are urgently needed, and in this study, we describe the anti-viral properties of a Spirulina (Arthrospira platensis) cold water extract. Anti-viral effects have previously been reported for extracts a...

  10. Serum amyloid P component binds to influenza A virus haemagglutinin and inhibits the virus infection in vitro

    Andersen, Ove; Vilsgaard Ravn, K; Juul Sørensen, I; Jonson, G; Holm Nielsen, E; Svehag, SE

    1997-01-01

    that SAP can bind to influenza A virus and inhibit agglutination of erythrocytes mediated by the virus subtypes H1N1, H2N2 and H3N2. SAP also inhibits the production of haemagglutinin (HA) an the cytopathogenic effect of influenza A virus in MDCK cells. The binding of SAP to the virus requires...

  11. Influenza A virus targets a cGAS-independent STING pathway that controls enveloped RNA viruses

    Holm, Christian K.; Rahbek, Stine H.; Gad, Hans Henrik; Bak, Rasmus O.; Jakobsen, Martin R; Jiang, Zhaozaho; Hansen, Anne Louise; Jensen, Simon K.; Sun, Chenglong; Thomsen, Martin K.; Laustsen, Anders; Nielsen, Camilla G.; Severinsen, Kasper; Xiong, Yingluo; Burdette, Dara L.

    2016-01-01

    Stimulator of interferon genes (STING) is known be involved in control of DNA viruses but has an unexplored role in control of RNA viruses. During infection with DNA viruses STING is activated downstream of cGAMP synthase (cGAS) to induce type I interferon. Here we identify a STING-dependent, cGAS-independent pathway important for full interferon production and antiviral control of enveloped RNA viruses, including influenza A virus (IAV). Further, IAV interacts with STING through its conserve...

  12. Influenza virus vaccine live intranasal--MedImmune vaccines: CAIV-T, influenza vaccine live intranasal.

    2003-01-01

    MedImmune Vaccines (formerly Aviron) has developed a cold-adapted live influenza virus vaccine [FluMist] that can be administered by nasal spray. FluMist is the first live virus influenza vaccine and also the first nasally administered vaccine to be marketed in the US. The vaccine will be formulated to contain live attenuated (att) influenza virus reassortants of the strains recommended by the US Public Health Service for each 'flu season. The vaccine is termed cold-adapted (ca) because the virus has been adapted to replicate efficiently at 25 degrees C in the nasal passages, which are below normal body temperature. The strains used in the seasonal vaccine will also be made temperature sensitive (ts) so that their replication is restricted at 37 degrees C (Type B strains) and 39 degrees C (Type A strains). The combined effect of the antigenic properties and the att, ca and ts phenotypes of the influenza strains contained in the vaccine enables the viruses to replicate in the nasopharynx to produce protective immunity. The original formulation of FluMist requires freezer storage throughout distribution. Because many international markets do not have distribution channels well suited to the sale of frozen vaccines, Wyeth and MedImmune are collaborating to develop a second generation, refrigerator-stable, liquid trivalent cold-adapted influenza vaccine (CAIV-T), which is in phase III trials. Initially, the frozen formulation will only be available in the US. For the 2003-2004 season, FluMist will contain A/New Caledonia/20/99 (H1N1), A/Panama/2007/99 (H3N2) (A/Moscow/10/99-like) and B/Hong Kong/330/2001. Aviron was acquired by MedImmune on 15 January 2002. Aviron is now a wholly-owned subsidiary of MedImmune and is called MedImmune Vaccines. Aviron acquired FluMist in March 1995 through a Co-operative Research and Development Agreement (CRADA) with the US NIAID, and a licensing agreement with the University of Michigan, Ann Arbor, USA. In June 2000, the CRADA was

  13. Protective Effect of Dietary Xylitol on Influenza A Virus Infection

    Sun Young Yin; Hyoung Jin Kim; Hong-Jin Kim

    2014-01-01

    Xylitol has been used as a substitute for sugar to prevent cavity-causing bacteria, and most studies have focused on its benefits in dental care. Meanwhile, the constituents of red ginseng (RG) are known to be effective in ameliorating the symptoms of influenza virus infection when they are administered orally for 14 days. In this study, we investigated the effect of dietary xylitol on influenza A virus infection (H1N1). We designed regimens containing various fractions of RG (RGs: whole extr...

  14. The hemagglutinin structure of an avian H1N1 influenza A virus

    Lin, Tianwei; Wang, Gengyan; Li, Anzhang; Zhang, Qian; Wu, Caiming; Zhang, Rongfu; Cai, Qixu; Song, Wenjun; Yuen, Kwok-Yung; (U. Hong Kong); (Inter. Inst. Infect. Imm.); (Xiamen)

    2009-09-15

    The interaction between hemagglutinin (HA) and receptors is a kernel in the study of evolution and host adaptation of H1N1 influenza A viruses. The notion that the avian HA is associated with preferential specificity for receptors with Sia{alpha}2,3Gal glycosidic linkage over those with Sia{alpha}2,6Gal linkage is not all consistent with the available data on H1N1 viruses. By x-ray crystallography, the HA structure of an avian H1N1 influenza A virus, as well as its complexes with the receptor analogs, was determined. The structures revealed no preferential binding of avian receptor analogs over that of the human analog, suggesting that the HA/receptor binding might not be as stringent as is commonly believed in determining the host receptor preference for some subtypes of influenza viruses, such as the H1N1 viruses. The structure also showed difference in glycosylation despite the preservation of related sequences, which may partly contribute to the difference between structures of human and avian origin.

  15. Novel avian influenza A (H7N9 virus induces impaired interferon responses in human dendritic cells.

    Veera Arilahti

    Full Text Available In March 2013 a new avian influenza A(H7N9 virus emerged in China and infected humans with a case fatality rate of over 30%. Like the highly pathogenic H5N1 virus, H7N9 virus is causing severe respiratory distress syndrome in most patients. Based on genetic analysis this avian influenza A virus shows to some extent adaptation to mammalian host. In the present study, we analyzed the activation of innate immune responses by this novel H7N9 influenza A virus and compared these responses to those induced by the avian H5N1 and seasonal H3N2 viruses in human monocyte-derived dendritic cells (moDCs. We observed that in H7N9 virus-infected cells, interferon (IFN responses were weak although the virus replicated as well as the H5N1 and H3N2 viruses in moDCs. H7N9 virus-induced expression of pro-inflammatory cytokines remained at a significantly lower level as compared to H5N1 virus-induced "cytokine storm" seen in human moDCs. However, the H7N9 virus was extremely sensitive to the antiviral effects of IFN-α and IFN-β in pretreated cells. Our data indicates that different highly pathogenic avian viruses may show considerable differences in their ability to induce host antiviral responses in human primary cell models such as moDCs. The unexpected appearance of the novel H7N9 virus clearly emphasizes the importance of the global influenza surveillance system. It is, however, equally important to systematically characterize in normal human cells the replication capacity of the new viruses and their ability to induce and respond to natural antiviral substances such as IFNs.

  16. Efficacy of canine influenza virus (H3N8) vaccine to decrease severity of clinical disease after co-challenge with canine influenza virus and Streptococcus equi subsp. Zooepidemicus

    Since first emerging into the North American canine population in 2004, canine influenza virus (CIV) subtype H3N8 has shown horizontal transmission among dogs, with a high level of adaptation to this species. Severity of disease is variable, and co-infection by other respiratory pathogens is an impo...

  17. Replication of avian, human and swine influenza viruses in porcine respiratory explants and association with sialic acid distribution

    Nauwynck Hans J

    2010-02-01

    Full Text Available Abstract Background Throughout the history of human influenza pandemics, pigs have been considered the most likely "mixing vessel" for reassortment between human and avian influenza viruses (AIVs. However, the replication efficiencies of influenza viruses from various hosts, as well as the expression of sialic acid (Sia receptor variants in the entire porcine respiratory tract have never been studied in detail. Therefore, we established porcine nasal, tracheal, bronchial and lung explants, which cover the entire porcine respiratory tract with maximal similarity to the in vivo situation. Subsequently, we assessed virus yields of three porcine, two human and six AIVs in these explants. Since our results on virus replication were in disagreement with the previously reported presence of putative avian virus receptors in the trachea, we additionally studied the distribution of sialic acid receptors by means of lectin histochemistry. Human (Siaα2-6Gal and avian virus receptors (Siaα2-3Gal were identified with Sambucus Nigra and Maackia amurensis lectins respectively. Results Compared to swine and human influenza viruses, replication of the AIVs was limited in all cultures but most strikingly in nasal and tracheal explants. Results of virus titrations were confirmed by quantification of infected cells using immunohistochemistry. By lectin histochemistry we found moderate to abundant expression of the human-like virus receptors in all explant systems but minimal binding of the lectins that identify avian-like receptors, especially in the nasal, tracheal and bronchial epithelium. Conclusions The species barrier that restricts the transmission of influenza viruses from one host to another remains preserved in our porcine respiratory explants. Therefore this system offers a valuable alternative to study virus and/or host properties required for adaptation or reassortment of influenza viruses. Our results indicate that, based on the expression of Sia

  18. The Timeline of Influenza Virus Shedding in Children and Adults in a Household Transmission Study of Influenza in Managua, Nicaragua.

    Ng, Sophia; Lopez, Roger; Kuan, Guillermina; Gresh, Lionel; Balmaseda, Angel; Harris, Eva; Gordon, Aubree

    2016-05-01

    In a household transmission study in Nicaragua, children under 6 years old had a longer duration of presymptomatic influenza virus shedding than adults. The duration of postsymptomatic influenza virus shedding was longest in children 0-5 years old, followed by children 6-15 years of age and adults. PMID:26910589

  19. Rapid preparation of mutated influenza hemagglutinins for influenza virus pandemic prevention.

    Nishioka, Ryosuke; Satomura, Atsushi; Yamada, Junki; Kuroda, Kouichi; Ueda, Mitsuyoshi

    2016-03-01

    Influenza viruses have periodically caused pandemic due to frequent mutation of viral proteins. Influenza viruses have two major membrane glycoproteins: hemagglutinin (HA) and neuraminidase (NA). Hemagglutinin plays a crucial role in viral entry, while NA is involved in the process of a viral escape. In terms of developing antiviral drugs, HA is a more important target than NA in the prevention of pandemic, since HA is likely to change the host specificity of a virus by acquiring mutations, thereby to increase the risk of pandemic. To characterize mutated HA functions, current approaches require immobilization of purified HA on plastic wells and carriers. These troublesome methods make it difficult to respond to emerging mutations. In order to address this problem, a yeast cell surface engineering approach was investigated. Using this technology, human HAs derived from various H1N1 subtypes were successfully and rapidly displayed on the yeast cell surface. The yeast-displayed HAs exhibited similar abilities to native influenza virus HAs. Using this system, human HAs with 190E and 225G mutations were shown to exhibit altered recognition specificities from human to avian erythrocytes. This system furthermore allowed direct measurement of HA binding abilities without protein purification and immobilization. Coupled with the ease of genetic manipulation, this system allows the simple and comprehensive construction of mutant protein libraries on yeast cell surface, thereby contributing to influenza virus pandemic prevention. PMID:26797882

  20. Patterns of evolution and host gene mimicry in influenza and other RNA viruses.

    Benjamin D Greenbaum

    2008-06-01

    Full Text Available It is well known that the dinucleotide CpG is under-represented in the genomic DNA of many vertebrates. This is commonly thought to be due to the methylation of cytosine residues in this dinucleotide and the corresponding high rate of deamination of 5-methycytosine, which lowers the frequency of this dinucleotide in DNA. Surprisingly, many single-stranded RNA viruses that replicate in these vertebrate hosts also have a very low presence of CpG dinucleotides in their genomes. Viruses are obligate intracellular parasites and the evolution of a virus is inexorably linked to the nature and fate of its host. One therefore expects that virus and host genomes should have common features. In this work, we compare evolutionary patterns in the genomes of ssRNA viruses and their hosts. In particular, we have analyzed dinucleotide patterns and found that the same patterns are pervasively over- or under-represented in many RNA viruses and their hosts suggesting that many RNA viruses evolve by mimicking some of the features of their host's genes (DNA and likely also their corresponding mRNAs. When a virus crosses a species barrier into a different host, the pressure to replicate, survive and adapt, leaves a footprint in dinucleotide frequencies. For instance, since human genes seem to be under higher pressure to eliminate CpG dinucleotide motifs than avian genes, this pressure might be reflected in the genomes of human viruses (DNA and RNA viruses when compared to those of the same viruses replicating in avian hosts. To test this idea we have analyzed the evolution of the influenza virus since 1918. We find that the influenza A virus, which originated from an avian reservoir and has been replicating in humans over many generations, evolves in a direction strongly selected to reduce the frequency of CpG dinucleotides in its genome. Consistent with this observation, we find that the influenza B virus, which has spent much more time in the human population, has

  1. Novel Reassortant Influenza A(H5N8) Viruses in Domestic Ducks, Eastern China

    Wu, Haibo; Peng, Xiaorong; Xu, Lihua; Jin, Changzhong; Cheng, Linfang; Lu, Xiangyun; Xie, Tiansheng; Yao, Hangping; Wu, Nanping

    2014-01-01

    Domestic ducks are natural reservoirs of avian influenza viruses and serve as reassortant hosts for new virus subtypes. We isolated 2 novel influenza A(H5N8) viruses from domestic ducks in eastern China, sequenced their genomes, and tested their pathogenicity in chickens and mice. Circulation of these viruses may pose health risks for humans.

  2. Competition between influenza A virus genome segments.

    Ivy Widjaja

    Full Text Available Influenza A virus (IAV contains a segmented negative-strand RNA genome. How IAV balances the replication and transcription of its multiple genome segments is not understood. We developed a dual competition assay based on the co-transfection of firefly or Gaussia luciferase-encoding genome segments together with plasmids encoding IAV polymerase subunits and nucleoprotein. At limiting amounts of polymerase subunits, expression of the firefly luciferase segment was negatively affected by the presence of its Gaussia luciferase counterpart, indicative of competition between reporter genome segments. This competition could be relieved by increasing or decreasing the relative amounts of firefly or Gaussia reporter segment, respectively. The balance between the luciferase expression levels was also affected by the identity of the untranslated regions (UTRs as well as segment length. In general it appeared that genome segments displaying inherent higher expression levels were more efficient competitors of another segment. When natural genome segments were tested for their ability to suppress reporter gene expression, shorter genome segments generally reduced firefly luciferase expression to a larger extent, with the M and NS segments having the largest effect. The balance between different reporter segments was most dramatically affected by the introduction of UTR panhandle-stabilizing mutations. Furthermore, only reporter genome segments carrying these mutations were able to efficiently compete with the natural genome segments in infected cells. Our data indicate that IAV genome segments compete for available polymerases. Competition is affected by segment length, coding region, and UTRs. This competition is probably most apparent early during infection, when limiting amounts of polymerases are present, and may contribute to the regulation of segment-specific replication and transcription.

  3. Influenza virus transmission is dependent on relative humidity and temperature.

    Anice C Lowen

    2007-10-01

    Full Text Available Using the guinea pig as a model host, we show that aerosol spread of influenza virus is dependent upon both ambient relative humidity and temperature. Twenty experiments performed at relative humidities from 20% to 80% and 5 degrees C, 20 degrees C, or 30 degrees C indicated that both cold and dry conditions favor transmission. The relationship between transmission via aerosols and relative humidity at 20 degrees C is similar to that previously reported for the stability of influenza viruses (except at high relative humidity, 80%, implying that the effects of humidity act largely at the level of the virus particle. For infected guinea pigs housed at 5 degrees C, the duration of peak shedding was approximately 40 h longer than that of animals housed at 20 degrees C; this increased shedding likely accounts for the enhanced transmission seen at 5 degrees C. To investigate the mechanism permitting prolonged viral growth, expression levels in the upper respiratory tract of several innate immune mediators were determined. Innate responses proved to be comparable between animals housed at 5 degrees C and 20 degrees C, suggesting that cold temperature (5 degrees C does not impair the innate immune response in this system. Although the seasonal epidemiology of influenza is well characterized, the underlying reasons for predominant wintertime spread are not clear. We provide direct, experimental evidence to support the role of weather conditions in the dynamics of influenza and thereby address a long-standing question fundamental to the understanding of influenza epidemiology and evolution.

  4. Perspective of Use of Antiviral Peptides against Influenza Virus

    Sylvie Skalickova

    2015-10-01

    Full Text Available The threat of a worldwide influenza pandemic has greatly increased over the past decade with the emergence of highly virulent avian influenza strains. The increased frequency of drug-resistant influenza strains against currently available antiviral drugs requires urgent development of new strategies for antiviral therapy, too. The research in the field of therapeutic peptides began to develop extensively in the second half of the 20th century. Since then, the mechanisms of action for several peptides and their antiviral prospect received large attention due to the global threat posed by viruses. Here, we discussed the therapeutic properties of peptides used in influenza treatment. Peptides with antiviral activity against influenza can be divided into three main groups. First, entry blocker peptides such as a Flupep that interact with influenza hemagglutinin, block its binding to host cells and prevent viral fusion. Second, several peptides display virucidal activity, disrupting viral envelopes, e.g., Melittin. Finally, a third set of peptides interacts with the viral polymerase complex and act as viral replication inhibitors such as PB1 derived peptides. Here, we present a review of the current literature describing the antiviral activity, mechanism and future therapeutic potential of these influenza antiviral peptides.

  5. Perspective of Use of Antiviral Peptides against Influenza Virus.

    Skalickova, Sylvie; Heger, Zbynek; Krejcova, Ludmila; Pekarik, Vladimir; Bastl, Karel; Janda, Jozef; Kostolansky, Frantisek; Vareckova, Eva; Zitka, Ondrej; Adam, Vojtech; Kizek, Rene

    2015-10-01

    The threat of a worldwide influenza pandemic has greatly increased over the past decade with the emergence of highly virulent avian influenza strains. The increased frequency of drug-resistant influenza strains against currently available antiviral drugs requires urgent development of new strategies for antiviral therapy, too. The research in the field of therapeutic peptides began to develop extensively in the second half of the 20(th) century. Since then, the mechanisms of action for several peptides and their antiviral prospect received large attention due to the global threat posed by viruses. Here, we discussed the therapeutic properties of peptides used in influenza treatment. Peptides with antiviral activity against influenza can be divided into three main groups. First, entry blocker peptides such as a Flupep that interact with influenza hemagglutinin, block its binding to host cells and prevent viral fusion. Second, several peptides display virucidal activity, disrupting viral envelopes, e.g., Melittin. Finally, a third set of peptides interacts with the viral polymerase complex and act as viral replication inhibitors such as PB1 derived peptides. Here, we present a review of the current literature describing the antiviral activity, mechanism and future therapeutic potential of these influenza antiviral peptides. PMID:26492266

  6. Heterogeneous and Dynamic Prevalence of Asymptomatic Influenza Virus Infections

    Furuya-Kanamori, Luis; Cox, Mitchell; Milinovich, Gabriel J.; Magalhaes, Ricardo J. Soares; Mackay, Ian M.

    2016-01-01

    Influenza infection manifests in a wide spectrum of severity, including symptomless pathogen carriers. We conducted a systematic review and meta-analysis of 55 studies to elucidate the proportional representation of these asymptomatic infected persons. We observed extensive heterogeneity among these studies. The prevalence of asymptomatic carriage (total absence of symptoms) ranged from 5.2% to 35.5% and subclinical cases (illness that did not meet the criteria for acute respiratory or influenza-like illness) from 25.4% to 61.8%. Statistical analysis showed that the heterogeneity could not be explained by the type of influenza, the laboratory tests used to detect the virus, the year of the study, or the location of the study. Projections of infection spread and strategies for disease control require that we identify the proportional representation of these insidious spreaders early on in the emergence of new influenza subtypes or strains and track how this rate evolves over time and space. PMID:27191967

  7. Influenza A Virus Entry Inhibitors Targeting the Hemagglutinin

    Shuwen Liu

    2013-01-01

    Full Text Available Influenza A virus (IAV has caused seasonal influenza epidemics and influenza pandemics, which resulted in serious threat to public health and socioeconomic impacts. Until now, only 5 drugs belong to two categories are used for prophylaxis and treatment of IAV infection. Hemagglutinin (HA, the envelope glycoprotein of IAV, plays a critical role in viral binding, fusion and entry. Therefore, HA is an attractive target for developing anti‑IAV drugs to block the entry step of IAV infection. Here we reviewed the recent progress in the study of conformational changes of HA during viral fusion process and the development of HA-based IAV entry inhibitors, which may provide a new choice for controlling future influenza pandemics.

  8. Genetic diversity among pandemic 2009 influenza viruses isolated from a transmission chain

    Fordyce, Sarah L; Bragstad, Karoline; Pedersen, Svend Stenvang; Jensen, Thøger Gorm; Gahrn-Hansen, Bente; Daniels, Rod; Hay, Alan; Kampmann, Marie-Louise; Bruhn, Christian Aw; Moreno-Mayar, J Victor; Avila Arcos, Maria del Carmen; Gilbert, M Thomas P; Nielsen, Lars P

    2013-01-01

    Influenza viruses such as swine-origin influenza A(H1N1) virus (A(H1N1)pdm09) generate genetic diversity due to the high error rate of their RNA polymerase, often resulting in mixed genotype populations (intra-host variants) within a single infection. This variation helps influenza to rapidly...

  9. A quantitative comet infection assay for influenza virus

    Lindsay, Stephen M.; Timm, Andrea; Yin, John

    2011-01-01

    The virus comet assay is a cell-based virulence assay used to evaluate an antiviral drug or antibody against a target virus. The comet assay differs from the plaque assay in allowing spontaneous flows in 6-well plates to spread virus. When implemented quantitatively the comet assay has been shown to have an order-of-magnitude greater sensitivity to antivirals than the plaque assay. In this study, a quantitative comet assay for influenza virus is demonstrated, and is shown to have a 13-fold in...

  10. The role of neutrophils in the upper and lower respiratory tract during influenza virus infection of mice

    Reading Patrick C

    2008-08-01

    Full Text Available Abstract Background Neutrophils have been shown to play a role in host defence against highly virulent and mouse-adapted strains of influenza virus, however it is not clear if an effective neutrophil response is an important factor moderating disease severity during infection with other virus strains. In this study, we have examined the role of neutrophils during infection of mice with influenza virus strain HKx31, a virus strain of the H3N2 subtype and of moderate virulence for mice, to determine the role of neutrophils in the early phase of infection and in clearance of influenza virus from the respiratory tract during the later phase of infection. Methods The anti-Gr-1 monoclonal antibody (mAb RB6-8C5 was used to (i identify neutrophils in the upper (nasal tissues and lower (lung respiratory tract of uninfected and influenza virus-infected mice, and (ii deplete neutrophils prior to and during influenza virus infection of mice. Results Neutrophils were rapidly recruited to the upper and lower airways following influenza virus infection. We demonstrated that use of mAb RB6-8C5 to deplete C57BL/6 (B6 mice of neutrophils is complicated by the ability of this mAb to bind directly to virus-specific CD8+ T cells. Thus, we investigated the role of neutrophils in both the early and later phases of infection using CD8+ T cell-deficient B6.TAP-/- mice. Infection of B6.TAP-/- mice with a low dose of influenza virus did not induce clinical disease in control animals, however RB6-8C5 treatment led to profound weight loss, severe clinical disease and enhanced virus replication throughout the respiratory tract. Conclusion Neutrophils play a critical role in limiting influenza virus replication during the early and later phases of infection. Furthermore, a virus strain of moderate virulence can induce severe clinical disease in the absence of an effective neutrophil response.