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Sample records for nonrecombinant h1n1 viruses

  1. 1918 pandemic H1N1 DNA vaccine protects ferrets against 2007 H1N1 virus infection

    DEFF Research Database (Denmark)

    Bragstad, Karoline; Martel, Cyril Jean-Marie; Aasted, Bent;

    of the H1N1 pandemic virus from 1918 induce protection in ferrets against infection with a H1N1 (A/New Caledonia/20/99(H1N1)) virus which was included in the conventional vaccine for the 2006-2007 season. The viruses are separated by a time interval of 89 years and differ by 21.2% in the HA1 protein...

  2. 1918 pandemic H1N1 DNA vaccine protects ferrets against 2007 H1N1 virus infection

    DEFF Research Database (Denmark)

    Bragstad, Karoline; Martel, Cyril Jean-Marie; Aasted, Bent

    of the H1N1 pandemic virus from 1918 induce protection in ferrets against infection with a H1N1 (A/New Caledonia/20/99(H1N1)) virus which was included in the conventional vaccine for the 2006-2007 season. The viruses are separated by a time interval of 89 years and differ by 21.2% in the HA1 protein......Influenza vaccines with the ability to induce immune responses cross-reacting with drifted virus variants would be of great advantage for vaccine development against seasonal and emerging new strains. We demonstrate that gene gun administrated DNA vaccine encoding HA and NA and/or NP and M proteins...

  3. Experimental infection with H1N1 European swine influenza virus protects pigs from an infection with the 2009 pandemic H1N1 human influenza virus.

    Science.gov (United States)

    Busquets, Núria; Segalés, Joaquim; Córdoba, Lorena; Mussá, Tufaria; Crisci, Elisa; Martín-Valls, Gerard E; Simon-Grifé, Meritxell; Pérez-Simó, Marta; Pérez-Maíllo, Monica; Núñez, Jose I; Abad, Francesc X; Fraile, Lorenzo; Pina, Sonia; Majó, Natalia; Bensaid, Albert; Domingo, Mariano; Montoya, María

    2010-01-01

    The recent pandemic caused by human influenza virus A(H1N1) 2009 contains ancestral gene segments from North American and Eurasian swine lineages as well as from avian and human influenza lineages. The emergence of this A(H1N1) 2009 poses a potential global threat for human health and the fact that it can infect other species, like pigs, favours a possible encounter with other influenza viruses circulating in swine herds. In Europe, H1N1, H1N2 and H3N2 subtypes of swine influenza virus currently have a high prevalence in commercial farms. To better assess the risk posed by the A(H1N1) 2009 in the actual situation of swine farms, we sought to analyze whether a previous infection with a circulating European avian-like swine A/Swine/Spain/53207/2004 (H1N1) influenza virus (hereafter referred to as SwH1N1) generated or not cross-protective immunity against a subsequent infection with the new human pandemic A/Catalonia/63/2009 (H1N1) influenza virus (hereafter referred to as pH1N1) 21 days apart. Pigs infected only with pH1N1 had mild to moderate pathological findings, consisting on broncho-interstitial pneumonia. However, pigs inoculated with SwH1N1 virus and subsequently infected with pH1N1 had very mild lung lesions, apparently attributed to the remaining lesions caused by SwH1N1 infection. These later pigs also exhibited boosted levels of specific antibodies. Finally, animals firstly infected with SwH1N1 virus and latter infected with pH1N1 exhibited undetectable viral RNA load in nasal swabs and lungs after challenge with pH1N1, indicating a cross-protective effect between both strains.

  4. Protective efficacy of an inactivated Eurasian avian-like H1N1 swine influenza vaccine against homologous H1N1 and heterologous H1N1 and H1N2 viruses in mice.

    Science.gov (United States)

    Sui, Jinyu; Yang, Dawei; Qiao, Chuanling; Xu, Huiyang; Xu, Bangfeng; Wu, Yunpu; Yang, Huanliang; Chen, Yan; Chen, Hualan

    2016-07-19

    Eurasian avian-like H1N1 (EA H1N1) swine influenza viruses are prevalent in pigs in Europe and Asia, but occasionally cause human infection, which raises concern about their pandemic potential. Here, we produced a whole-virus inactivated vaccine with an EA H1N1 strain (A/swine/Guangxi/18/2011, SW/GX/18/11) and evaluated its efficacy against homologous H1N1 and heterologous H1N1 and H1N2 influenza viruses in mice. A strong humoral immune response, which we measured by hemagglutination inhibition (HI) and virus neutralization (VN), was induced in the vaccine-inoculated mice upon challenge. The inactivated SW/GX/18/11 vaccine provided complete protection against challenge with homologous SW/GX/18/11 virus in mice and provided effective protection against challenge with heterologous H1N1 and H1N2 viruses with distinctive genomic combinations. Our findings suggest that this EA H1N1 vaccine can provide protection against both homologous H1N1 and heterologous H1N1 or H1N2 virus infection. As such, it is an excellent vaccine candidate to prevent H1N1 swine influenza.

  5. H1N1 influenza A virus neuraminidase modulates infectivity in mice.

    Science.gov (United States)

    Ferraris, Olivier; Escuret, Vanessa; Bouscambert, Maude; Casalegno, Jean-Sébastien; Jacquot, Frédéric; Raoul, Hervé; Caro, Valérie; Valette, Martine; Lina, Bruno; Ottmann, Michèle

    2012-03-01

    In the 2years since the onset of the H1N1 2009 pandemic virus (H1N1pdm09), sporadic cases of oseltamivir-resistant viruses have been reported. We investigated the impact of oseltamivir-resistant neuraminidase from H1N1 Brisbane-like (seasonal) and H1N1pdm09 viruses on viral pathogenicity in mice. Reassortant viruses with the neuraminidase from seasonal H1N1 virus were obtained by co-infection of a H1N1pdm09 virus and an oseltamivir-resistant H1N1 Brisbane-like virus. Oseltamivir-resistant H1N1pdm09 viruses were also isolated from patients. After biochemical characterization, the pathogenicity of these viruses was assessed in a murine model. We confirmed a higher infectivity, in mice, of the H1N1pdm09 virus compared to seasonal viruses. Surprisingly, the oseltamivir-resistant H1N1pdm09 virus was more infectious than its sensitive counterpart. Moreover, the association of H1N1pdm09 hemagglutinin and an oseltamivir-resistant neuraminidase improved the infectivity of reassortant viruses in mice, regardless of the NA origin: seasonal (Brisbane-like) or pandemic strain. This study highlights the need to closely monitor the emergence of oseltamivir-resistant viruses. Copyright © 2012 Elsevier B.V. All rights reserved.

  6. Influenza A pandemic (H1N1) 2009 virus infection

    Institute of Scientific and Technical Information of China (English)

    BAI Lu; CAO Bin; WANG Chen

    2011-01-01

    The clinical spectrum of the 2009 pandemic influenza A (H1N1) infection ranged from self-limited mild illness to progressive pneumonia,or even a fatal outcome.We summarize the clinical manifestations,risk factors for severe and fatal cases,pathologic findings and treatment of this disease in this paper based on current reports from different regions of the world.

  7. North American triple reassortant and Eurasian H1N1 swine influenza viruses do not readily reassort to generate a 2009 pandemic H1N1-like virus.

    Science.gov (United States)

    Ma, Wenjun; Liu, Qinfang; Qiao, Chuanling; del Real, Gustavo; García-Sastre, Adolfo; Webby, Richard J; Richt, Jürgen A

    2014-03-11

    The 2009 pandemic H1N1 virus (pH1N1) was derived through reassortment of North American triple reassortant and Eurasian avian-like swine influenza viruses (SIVs). To date, when, how and where the pH1N1 arose is not understood. To investigate viral reassortment, we coinfected cell cultures and a group of pigs with or without preexisting immunity with a Eurasian H1N1 virus, A/Swine/Spain/53207/2004 (SP04), and a North American triple reassortant H1N1 virus, A/Swine/Kansas/77778/2007 (KS07). The infected pigs were cohoused with one or two groups of contact animals to investigate viral transmission. In coinfected MDCK or PK15 continuous cell lines with KS07 and SP04 viruses, more than 20 different reassortant viruses were found. In pigs without or with preexisting immunity (immunized with commercial inactivated swine influenza vaccines) and coinfected with both viruses, six or seven reassortant viruses, as well as the parental viruses, were identified in bronchoalveolar lavage fluid samples from the lungs. Interestingly, only one or two viruses transmitted to and were detected in contact animals. No reassortant containing a gene constellation similar to that of pH1N1 virus was found in either coinfected cells or pigs, indicating that the reassortment event that resulted in the generation of this virus is a rare event that likely involved specific viral strains and/or a favorable, not-yet-understood environment. IMPORTANCE The 2009 pandemic-like H1N1 virus could not be reproduced either in cell cultures or in pigs coinfected with North American triple reassortant H1N1 and Eurasian H1N1 swine influenza viruses. This finding suggests that the generation of the 2009 pandemic H1N1 virus by reassortment was a rare event that likely involved specific viral strains and unknown factors. Different reassortant viruses were detected in coinfected pigs with and without preexisting immunity, indicating that host immunity plays a relevant role in driving viral reassortment of

  8. Protection of mice against lethal challenge with 2009 H1N1 influenza A virus by 1918-like and classical swine H1N1 based vaccines.

    Directory of Open Access Journals (Sweden)

    Balaji Manicassamy

    2010-01-01

    Full Text Available The recent 2009 pandemic H1N1 virus infection in humans has resulted in nearly 5,000 deaths worldwide. Early epidemiological findings indicated a low level of infection in the older population (>65 years with the pandemic virus, and a greater susceptibility in people younger than 35 years of age, a phenomenon correlated with the presence of cross-reactive immunity in the older population. It is unclear what virus(es might be responsible for this apparent cross-protection against the 2009 pandemic H1N1 virus. We describe a mouse lethal challenge model for the 2009 pandemic H1N1 strain, used together with a panel of inactivated H1N1 virus vaccines and hemagglutinin (HA monoclonal antibodies to dissect the possible humoral antigenic determinants of pre-existing immunity against this virus in the human population. By hemagglutinination inhibition (HI assays and vaccination/challenge studies, we demonstrate that the 2009 pandemic H1N1 virus is antigenically similar to human H1N1 viruses that circulated from 1918-1943 and to classical swine H1N1 viruses. Antibodies elicited against 1918-like or classical swine H1N1 vaccines completely protect C57B/6 mice from lethal challenge with the influenza A/Netherlands/602/2009 virus isolate. In contrast, contemporary H1N1 vaccines afforded only partial protection. Passive immunization with cross-reactive monoclonal antibodies (mAbs raised against either 1918 or A/California/04/2009 HA proteins offered full protection from death. Analysis of mAb antibody escape mutants, generated by selection of 2009 H1N1 virus with these mAbs, indicate that antigenic site Sa is one of the conserved cross-protective epitopes. Our findings in mice agree with serological data showing high prevalence of 2009 H1N1 cross-reactive antibodies only in the older population, indicating that prior infection with 1918-like viruses or vaccination against the 1976 swine H1N1 virus in the USA are likely to provide protection against the 2009

  9. Genetic correlation between current circulating H1N1 swine and human influenza viruses.

    Science.gov (United States)

    Lu, Lu; Yin, Yanbo; Sun, Zhongsheng; Gao, Lei; Gao, George F; Liu, Sidang; Sun, Lei; Liu, Wenjun

    2010-11-01

    H1N1 is the main subtype influenza A virus circulating in human and swine population, and has long been a threat to economy and public health. To explore the genetic correlation between current circulating H1N1 swine and human influenza viruses. Three new H1N1 swine influenza viruses (SIVs) were isolated and genomes sequencing were conducted followed by phylogenetic and molecular analysis of all swine and human H1N1 influenza viruses isolated in China in the past five years. Homology and phylogenetic analysis revealed that the three isolates possessed different characteristics: the genome of A/Swine/Shandong/1112/2008 was closely related to that of classical H1N1 SIV, while A/Swine/Shandong/1123/2008 was a reassortant with NS gene from the human-like H3N2 influenza virus and other genes from the classical H1N1 SIV, and A/Swine/Fujian/0325/2008 fell into a lineage of seasonal human H1N1 influenza viruses. Genetically, 2009 H1N1 influenza A viruses (2009 H1N1) in China were contiguous to the SIV lineages rather than the seasonal H1N1 human influenza virus's lineage. Furthermore, molecular analysis among human and swine influenza viruses provided more detail information for understanding their genetic correlation. These results suggested that in China in the past five years, the classical, avian-like and human-like H1N1 SIV existed in swine herds and the reassortment between H1N1 swine and H3N2 human influenza viruses was identified. In addition, the present data showed no evidence to support a strong correlation between the 2009 H1N1 and the swine influenza virus circulating in China. Copyright © 2010 Elsevier B.V. All rights reserved.

  10. Co-circulation of pandemic 2009 H1N1, classical swine H1N1 and avian-like swine H1N1 influenza viruses in pigs in China.

    Science.gov (United States)

    Chen, Yan; Zhang, Jian; Qiao, Chuanling; Yang, Huanliang; Zhang, Ying; Xin, Xiaoguang; Chen, Hualan

    2013-01-01

    The pandemic A/H1N1 influenza viruses emerged in both Mexico and the United States in March 2009, and were transmitted efficiently in the human population. They were transmitted occasionally from humans to other mammals including pigs, dogs and cats. In this study, we report the isolation and genetic analysis of novel viruses in pigs in China. These viruses were related phylogenetically to the pandemic 2009 H1N1 influenza viruses isolated from humans and pigs, which indicates that the pandemic virus is currently circulating in swine populations, and this hypothesis was further supported by serological surveillance of pig sera collected within the same period. Furthermore, we isolated another two H1N1 viruses belonging to the lineages of classical swine H1N1 virus and avian-like swine H1N1 virus, respectively. Multiple genetic lineages of H1N1 viruses are co-circulating in the swine population, which highlights the importance of intensive surveillance for swine influenza in China.

  11. Oseltamivir-resistant influenza virus A (H1N1), Europe, 2007/08 season.

    NARCIS (Netherlands)

    Meijer, A.; Lackenby, A.; Hungnes, O.; Lina, B.; Werf, S. van der; Schweiger, B.; Opp, M.; Paget, J.; Kassteele, J. van de; Hay, A.; Zambon, M.

    2009-01-01

    In Europe, the 2007/08 winter season was dominated by influenza virus A (H1N1) circulation through week 7, followed by influenza B virus from week 8 onward. Oseltamivir-resistant influenza viruses A (H1N1) (ORVs) with H275Y mutation in the neuraminidase emerged independently of drug use. By country,

  12. Serologic Cross-Reactivity with Pandemic (H1N1) 2009 Virus in Pigs, Europe

    Science.gov (United States)

    Kyriakis, Constantinos S.; Olsen, Christopher W.; Carman, Susy; Brown, Ian H.; Brookes, Sharon M.; Van Doorsselaere, Jan

    2010-01-01

    We tested serum samples from pigs infected or vaccinated with European swine influenza viruses (SIVs) in hemagglutination-inhibition assays against pandemic (H1N1) 2009 virus and related North American SIVs. We found more serologic cross-reaction than expected. Data suggest pigs in Europe may have partial immunity to pandemic (H1N1) 2009 virus. PMID:20031049

  13. Influenza virus A(H1N1)2009 antibody-dependent cellular cytotoxicity in young children prior to the H1N1 pandemic.

    Science.gov (United States)

    Mesman, Annelies W; Westerhuis, Brenda M; Ten Hulscher, Hinke I; Jacobi, Ronald H; de Bruin, Erwin; van Beek, Josine; Buisman, Annemarie M; Koopmans, Marion P; van Binnendijk, Robert S

    2016-09-01

    Pre-existing immunity played a significant role in protection during the latest influenza A virus H1N1 pandemic, especially in older age groups. Structural similarities were found between A(H1N1)2009 and older H1N1 virus strains to which humans had already been exposed. Broadly cross-reactive antibodies capable of neutralizing the A(H1N1)2009 virus have been implicated in this immune protection in adults. We investigated the serological profile of a group of young children aged 9 years (n=55), from whom paired blood samples were available, just prior to the pandemic wave (March 2009) and shortly thereafter (March 2010). On the basis of A(H1N1)2009 seroconversion, 27 of the 55 children (49 %) were confirmed to be infected between these two time points. Within the non-infected group of 28 children (51 %), high levels of seasonal antibodies to H1 and H3 HA1 antigens were detected prior to pandemic exposure, reflecting past infection with H1N1 and H3N2, both of which had circulated in The Netherlands prior to the pandemic. In some children, this reactivity coincided with specific antibody reactivity against A(H1N1)2009. While these antibodies were not able to neutralize the A(H1N1)2009 virus, they were able to mediate antibody-dependent cellular cytotoxicity (ADCC) in vitro upon interaction with the A(H1N1)2009 virus. This finding suggests that cross-reactive antibodies could contribute to immune protection in children via ADCC.

  14. Novel influenza A(H1N1) 2009 in vitro reassortant viruses with oseltamivir resistance.

    Science.gov (United States)

    Ottmann, Michèle; Duchamp, Maude Bouscambert; Casalegno, Jean-Sébastien; Frobert, Emilie; Moulès, Vincent; Ferraris, Olivier; Valette, Martine; Escuret, Vanessa; Lina, Bruno

    2010-01-01

    With the recent emergence of the novel A(H1N1) virus in 2009, the efficacy of available drugs, such as neuraminidase (NA) inhibitors, is of great concern for good patient care. Influenza viruses are known to be able to acquire resistance. In 2007, A(H1N1) viruses related to A/Brisbane/59/2007 (H1N1) (A[H1N1] Brisbane-like virus), which are naturally resistant to oseltamivir, emerged. Resistance to oseltamivir can be acquired either by spontaneous mutation in the NA (H275Y in N1), or by reassortment with a mutated NA. It is therefore crucial to determine the risk of pandemic A(H1N1) 2009 virus acquiring resistance against oseltamivir by reassortment. We estimated the capacity of reassortment between the A(H1N1) 2009 virus and an oseltamivir-resistant A(H1N1) Brisbane-like virus by in vitro coinfections of influenza-permissive cells. The screening and the analysis of reassortant viruses was performed by specific reverse transcriptase PCRs and by sequencing. Out of 50 analysed reassortant viruses, two harboured the haemagglutinin (HA) segment from the pandemic A(H1N1) 2009 virus and the mutated NA originated from the A(H1N1) Brisbane-like virus. The replicating capacities of these viruses were measured, showing no difference as compared to the two parental strains, suggesting that acquisition of the mutated NA segment did not impair viral fitness in vitro. Our results suggest that the novel A(H1N1) 2009 virus can acquire by in vitro genetic reassortment the H275Y mutated NA segment conferring resistance to oseltamivir.

  15. Genome evolution of novel influenza A (H1N1)viruses in humans

    Institute of Scientific and Technical Information of China (English)

    KOU Zheng; HU SongNian; LI TianXian

    2009-01-01

    The epidemic situation of A H1N1 flu arose in North America in April 2009,which rapidly expanded to three continents of Europe,Asia and Africa,with the risk ranking up to 5.Until May 13th,the flu virus of A H1N1 had spread into 33 countries and regions,with a laboratory confirmed case number of 5728,including 61 deaths.Based on IRV and EpiFluDB database,425 parts of A H1N1 flu virus sequence were achieved,followed by sequenced comparison and evolution analysis.The results showed that the current predominant A H1N1 flu virus was a kind of triple reassortment A flu virus:(i) HA,NA,MP,NP and NS originated from swine influenza virus;PB2 and PA originated from bird influenza virus;PB1 originated from human influenza virus.(ii) The origin of swine influenza virus could be subdivided as follows:HA,NP and NS originated from classic swine influenza virus of H1N1 subtype;NA and MP originated from bird origin swine influenza virus of H1N1 subtype.(iii) A H1N1 flu virus experienced no significant mutation during the epidemic spread,accompanied with no reassortment of the virus genome.In the paper,the region of the representative strains for sequence analysis (A/California/04/2009 (H1N1) and A/Mexico/4486/2009 (H1N1)) included USA and Mexico and was relatively wide,which suggested that the analysis results were convincing.

  16. Antigenic Patterns and Evolution of the Human Influenza A (H1N1) Virus.

    Science.gov (United States)

    Liu, Mi; Zhao, Xiang; Hua, Sha; Du, Xiangjun; Peng, Yousong; Li, Xiyan; Lan, Yu; Wang, Dayan; Wu, Aiping; Shu, Yuelong; Jiang, Taijiao

    2015-09-28

    The influenza A (H1N1) virus causes seasonal epidemics that result in severe illnesses and deaths almost every year. A deep understanding of the antigenic patterns and evolution of human influenza A (H1N1) virus is extremely important for its effective surveillance and prevention. Through development of antigenicity inference method for human influenza A (H1N1), named PREDAC-H1, we systematically mapped the antigenic patterns and evolution of the human influenza A (H1N1) virus. Eight dominant antigenic clusters have been inferred for seasonal H1N1 viruses since 1977, which demonstrated sequential replacements over time with a similar pattern in Asia, Europe and North America. Among them, six clusters emerged first in Asia. As for China, three of the eight antigenic clusters were detected in South China earlier than in North China, indicating the leading role of South China in H1N1 transmission. The comprehensive view of the antigenic evolution of human influenza A (H1N1) virus can help formulate better strategy for its prevention and control.

  17. Structural Basis of Preexisting Immunity to the 2009 H1N1 Pandemic Influenza Virus

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Rui; Ekiert, Damian C.; Krause, Jens C.; Hai, Rong; Crowe, Jr., James E.; Wilson, Ian A. (Sinai); (Scripps); (Vanderbilt)

    2010-05-25

    The 2009 H1N1 swine flu is the first influenza pandemic in decades. The crystal structure of the hemagglutinin from the A/California/04/2009 H1N1 virus shows that its antigenic structure, particularly within the Sa antigenic site, is extremely similar to those of human H1N1 viruses circulating early in the 20th century. The cocrystal structure of the 1918 hemagglutinin with 2D1, an antibody from a survivor of the 1918 Spanish flu that neutralizes both 1918 and 2009 H1N1 viruses, reveals an epitope that is conserved in both pandemic viruses. Thus, antigenic similarity between the 2009 and 1918-like viruses provides an explanation for the age-related immunity to the current influenza pandemic.

  18. Oseltamivir-resistant pandemic influenza a (H1N1) 2009 viruses in Spain.

    Science.gov (United States)

    Ledesma, Juan; Vicente, Diego; Pozo, Francisco; Cilla, Gustavo; Castro, Sonia Pérez; Fernández, Jonathan Suárez; Ruiz, Mercedes Pérez; Navarro, José María; Galán, Juan Carlos; Fernández, Mirian; Reina, Jordi; Larrauri, Amparo; Cuevas, María Teresa; Casas, Inmaculada; Breña, Pilar Pérez

    2011-07-01

    Pandemic influenza A (H1N1) 2009 virus appeared in Spain on April 25, 2009 for the first time. This new virus was adamantane-resistant but it was sensitive to neuraminidase (NA) inhibitors oseltamivir and zanamivir. To detect oseltamivir-resistant pandemic influenza A (H1N1) 2009 viruses by the Spanish Influenza Surveillance System (SISS) and a possible spread of oseltamivir-resistant viruses in Spain since starting of the pandemic situation. A total of 1229 respiratory samples taken from 413 severe and 766 non-severe patients with confirmed viral detection of pandemic influenza A (H1N1) 2009 viruses from different Spanish regions were analyzed for the specific detection of the H275Y mutation in NA between April 2009 and May 2010. H275Y NA substitution was found in 8 patients infected with pandemic influenza A (H1N1) 2009 viruses collected in November and December 2009 and in January 2010. All oseltamivir-resistant viruses were detected in severe patients (8/413, 1.93%) who previously received treatment with oseltamivir. Six of these patients were immunocompromised. In Spain, the number of oseltamivir-resistant pandemic influenza A (H1N1) 2009 viruses is until now very low. No evidence for any spread of oseltamivir-resistant H1N1 viruses is achieved in our Country. Copyright © 2011 Elsevier B.V. All rights reserved.

  19. Close Relationship between the 2009 H1N1 Virus and South Dakota AIV Strains

    Institute of Scientific and Technical Information of China (English)

    Cun Li; Xiao-ping An; Zhi-qiang Mi; Da-bin Liu; Huan-huan Jiang; Bo Pan; Sheng Wang; Bin Chen; Yi-gang Tong

    2011-01-01

    Although previous publications suggest the 2009 pandemic influenza A(H1N1)virus was reassorted from swine viruses of North America and Eurasia, the immediate ancestry still remains elusive due to the big evolutionary distance between the 2009 H1N1 virus and the previously isolated strains. Since the unveiling of the2009 H1N1 influenza, great deal of interest has been drawn to influenza, consequently a large number of influenza virus sequences have been deposited into the public sequence databases. Blast analysis demonstrated that the recently submitted 2007 South Dakota avian influenza virus strains and other North American avian strains contained genetic segments very closely related to the 2009 H1N1 virus, which suggests these avian influenza viruses are very close relatives of the 2009 H1N1 virus. Phylogenetic analyses also indicate that the2009 H1N1 viruses are associated with both avian and swine influenza viruses circulating in North America. Since the migrating wild birds are preferable to pigs as the carrier to spread the influenza viruses across vast distances, it is very likely that birds played an important role in the inter-continental evolution of the 2009 H1N1virus. It is essential to understand the evolutionary route of the emerging influenza virus in order to find a way to prevent further emerging cases. This study suggests the close relationship between 2009 pandemic virus and the North America avian viruses and underscores enhanced surveillance of influenza in birds for understanding the evolution of the 2009 pandemic influenza.

  20. Oseltamivir-Resistant Pandemic (H1N1) 2009 Virus, Mexico

    Science.gov (United States)

    Ramirez-Gonzalez, José Ernesto; Gonzalez-Duran, Elizabeth; Alcantara-Perez, Patricia; Wong-Arambula, Claudia; Olivera-Diaz, Hiram; Cortez-Ortiz, Iliana; Barrera-Badillo, Gisela; Nguyen, Ha; Gubareva, Larisa; Lopez-Martinez, Irma; Díaz-Quiñonez, Jose Alberto; Lezana-Fernández, Miguel Angel; Gatell-Ramírez, Hugo Lopez; Villalobos, Jose Angel Cordova; Hernández-Avila, Mauricio

    2011-01-01

    During May 2009–April 2010, we analyzed 692 samples of pandemic (H1N1) 2009 virus from patients in Mexico. We detected the H275Y substitution of the neuraminidase gene in a specimen from an infant with pandemic (H1N1) 2009 who was treated with oseltamivir. This virus was susceptible to zanamivir and resistant to adamantanes and oseltamivir. PMID:21291607

  1. 2009 H1N1 influenza virus infection and necrotizing pneumonia treated with extracorporeal membrane oxygenation

    Directory of Open Access Journals (Sweden)

    Suntae Ji

    2011-08-01

    Full Text Available A 3-year-old girl with acute respiratory distress syndrome due to a H1N1 2009 influenza virus infection was complicated by necrotizing pneumonia was successfully treated with extracorporeal membrane oxygenation (ECMO. This is the first reported case in which a pediatric patient was rescued with ECMO during the H1N1 influenza epidemic in Korea in 2009.

  2. Molecular epidemiology and complete genome characterization of H1N1pdm virus from India.

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    Shashi Sharma

    Full Text Available BACKGROUND: Influenza A virus is one of world's major uncontrolled pathogen, causing seasonal epidemic as well as global pandemic. This was evidenced by recent emergence and continued prevalent 2009 swine origin pandemic H1N1 Influenza A virus, provoking first true pandemic in the past 40 years. In the course of its evolution, the virus acquired many mutations and multiple unidentified molecular determinants are likely responsible for the ability of the 2009 H1N1 virus to cause increased disease severity in humans. Availability of limited data on complete genome hampers the continuous monitoring of this type of events. Outbreaks with considerable morbidity and mortality have been reported from all parts of the country. METHODS/RESULTS: Considering a large number of clinical cases of infection complete genome based sequence characterization of Indian H1N1pdm virus and their phylogenetic analysis with respect to circulating global viruses was undertaken, to reveal the phylodynamic pattern of H1N1pdm virus in India from 2009-2011. The Clade VII was observed as a major circulating clade in phylogenetic analysis. Selection pressure analysis revealed 18 positively selected sites in major surface proteins of H1N1pdm virus. CONCLUSIONS: This study clearly revealed that clade VII has been identified as recent circulating clade in India as well globally. Few clade VII specific well identified markers undergone positive selection during virus evolution. Continuous monitoring of the H1N1pdm virus is warranted to track of the virus evolution and further transmission. This study will serve as a baseline data for future surveillance and also for development of suitable therapeutics.

  3. The seroprevalence of pandemic influenza H1N1 (2009 virus in China.

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    Cuiling Xu

    Full Text Available BACKGROUND: Mainland China experienced pandemic influenza H1N1 (2009 virus (pH1N1 with peak activity during November-December 2009. To understand the geographic extent, risk factors, and attack rate of pH1N1 infection in China we conducted a nationwide serological survey to determine the prevalence of antibodies to pH1N1. METHODOLOGY/PRINCIPAL FINDINGS: Stored serum samples (n = 2,379 collected during 2006-2008 were used to estimate baseline serum reactogenicity to pH1N1. In January 2010, we used a multistage-stratified random sampling method to select 50,111 subjects who met eligibility criteria and collected serum samples and administered a standardized questionnaire. Antibody response to pH1N1 was measured using haemagglutination inhibition (HI assay and the weighted seroprevalence was calculated using the Taylor series linearization method. Multivariable logistic regression analyses were used to examine risk factors for pH1N1 seropositivity. Baseline seroprevalence of pH1N1 antibody (HI titer ≥40 was 1.2%. The weighted seroprevalence of pH1N1 among the Chinese population was 21.5%(vaccinated: 62.0%; unvaccinated: 17.1%. Among unvaccinated participants, those aged 6-15 years (32.9% and 16-24 years (30.3% had higher seroprevalence compared with participants aged 25-59 years (10.7% and ≥60 years (9.9%, P<0.0001. Children in kindergarten and students had higher odds of seropositivity than children in family care (OR: 1.36 and 2.05, respectively. We estimated that 207.7 million individuals (15.9% experienced pH1N1 infection in China. CONCLUSIONS/SIGNIFICANCE: The Chinese population had low pre-existing immunity to pH1N1 and experienced a relatively high attack rate in 2009 of this virus. We recommend routine control measures such as vaccination to reduce transmission and spread of seasonal and pandemic influenza viruses.

  4. Mongrelised genetics of H1N1 virus: A bird′s eyeview

    Directory of Open Access Journals (Sweden)

    Nagarathna C

    2010-01-01

    Full Text Available H1N1 influenza, also known as "novel H1N1 virus" has led to a "global outcry." This virus is more virulent when compared with other seasonal flu viruses. Virulence may change as the adaptive mutation gene increases within the virus. A study at the US Centre for Disease Control and Prevention published in May 2009 found that children had no preexisting immunity to the new strain as they showed no cross-reactive antibody reaction when compared with adults aged 18-64 years, who showed a cross-reactive antibody reaction of 6-9% and older adults with 33% immunity. This review article depicts H1N1 virus, its virulence with genetic evolution potential and preventive protocol for the dental professionals. This would allow us to comprehend the changes in the disease process and contribute in its prevention as "prevention is better than cure."

  5. Initial incursion of pandemic (H1N1) 2009 influenza A virus into European pigs.

    Science.gov (United States)

    Welsh, M D; Baird, P M; Guelbenzu-Gonzalo, M P; Hanna, A; Reid, S M; Essen, S; Russell, C; Thomas, S; Barrass, L; McNeilly, F; McKillen, J; Todd, D; Harkin, V; McDowell, S; Choudhury, B; Irvine, R M; Borobia, J; Grant, J; Brown, I H

    2010-05-22

    The initial incursion of pandemic (H1N1) 2009 influenza A virus (pH1N1) into a European pig population is reported. Diagnosis of swine influenza caused by pandemic virus was made during September 2009 following routine submission of samples for differential diagnosis of causative agents of respiratory disease, including influenza A virus. All four pigs (aged six weeks) submitted for investigation from a pig herd of approximately 5000 animals in Northern Ireland, experiencing acute-onset respiratory signs in finishing and growing pigs, were positive by immunofluorescence for influenza A. Follow-up analysis of lung tissue homogenates by real-time RT-PCR confirmed the presence of pH1N1. The virus was subsequently detected on two other premises in Northern Ireland; on one premises, detection followed the pre-export health certification testing of samples from pigs presumed to be subclinically infected as no clinical signs were apparent. None of the premises was linked to another epidemiologically. Sequencing of the haemagglutinin and neuraminidase genes revealed high nucleotide identity (>99.4 per cent) with other pH1N1s isolated from human beings. Genotypic analyses revealed all gene segments to be most closely related to those of contemporary pH1N1 viruses in human beings. It is concluded that all three outbreaks occurred independently, potentially as a result of transmission of the virus from human beings to pigs.

  6. Experimental pandemic (H1N1) 2009 virus infection of cats

    NARCIS (Netherlands)

    J.M.A. van den Brand (Judith); K.J. Stittelaar (Koert); G. van Amerongen (Geert); M.W.G. van de Bildt (Marco); L.M.E. Leijten (Lonneke); T. Kuiken (Thijs); A.D.M.E. Osterhaus (Albert)

    2010-01-01

    textabstractTo demonstrate that pandemic (H1N1) 2009 virus may cause respiratory disease in cats, we intratracheally infected cats. Diffuse alveolar damage developed. Seroconversion of sentinel cats indicated cat-to-cat virus transmission. Unlike in cats infected with highly pathogenic avian influen

  7. Phylogenetic analysis of surface proteins of novel H1N1 virus isolated from 2009 pandemic.

    Science.gov (United States)

    Danishuddin, Mohd; Khan, Shahper N; Khan, Asad U

    2009-09-30

    Swine Influenza Virus (H1N1) is a known causative agent of swine flu. Transmission of Swine Influenza Virus form pig to human is not a common event and may not always cause human influenza. The 2009 outbreak by subtype H1N1 in humans is due to transfer of Swine Influenza Virus from pig to human. Thus to analyze the origin of this novel virus we compared two surface proteins (HA and NA) with influenza viruses of swine, avian and humans isolates recovered from 1918 to 2008 outbreaks. Phylogenetic analyses of hemagglutinin gene from 2009 pandemic found to be clustered with swine influenza virus (H1N2) circulated in U.S.A during the 1999-2004 outbreaks. Whereas, neuraminidase gene was clustered with H1N1 strains isolated from Europe and Asia during 1992-2007 outbreaks. This study concludes that the new H1N1 strain appeared in 2009 outbreak with high pathogenicity to human was originated as result of re-assortment (exchange of gene). Moreover, our data also suggest that the virus will remain sensitive to the pre-existing therapeutic strategies.

  8. [Effect of Yunnan herb Laggera pterodonta against influenza A (H1N1) virus in vitro].

    Science.gov (United States)

    Xia, Xiao-ling; Sun, Qiang-ming; Wang, Xiao-dan; Zhao, Yu-jiao; Yang, Zi-feng; Huang, Qing-hui; Jiang, Zhi-hong; Wang, Xin-hua; Zhang, Rong-ping

    2015-09-01

    Laggera pterodonta is commonly used for treating influenza in Southwest China, especially in Yunnnan province. The main clinical effects of L. pterodonta include anti-influenza, anti-microbial, anti-inflammatory. To investigate the anti-influenza A (H1N1) virus effect of L. pterodonta, neutralization inhibition and proliferation inhibition tests were performed. MDCK culture method was used to observe the cytopathic effect (CPE) of extracts from L. pterodonta in inhibiting influenza A (H1N1) virus and haemagglutination titre of H1N1 virus in vitro. The culture medium were collected at 24 h, 48 h, 72 h, 96 h, and detected by Real time RT-PCR, in order to compare the effect of different extracts from L. pterodonta on in vitro proliferation of H1N1, virus. The result of neutralization inhibition test showed that hemagglutination titer of ethyl acetate extract were 8 times lower at 72 h; in proliferation inhibition test, hemagglutination titer of ethyl acetate extracts reduced by 2 and 4 times. According to the results of Real time RT-PCR test, the H1N1 inhibition ratio of ethyl acetate extract was 72.5%, while the proliferation inhibition ratio of ethyl acetate extract was 25.3%; as for petroleum ether extracts, the H1N1 inhibition ratio was 60.2%, while the proliferation inhibition ratio was 81.4%. In conclusion, both ethyl acetate extract and petroleum ether extract of L. pterodonta have significant neutralization and direct proliferation inhibition effects on influenza A virus.

  9. Susceptibility of turkeys to pandemic-H1N1 virus by reproductive tract insemination

    Directory of Open Access Journals (Sweden)

    Suarez David L

    2010-02-01

    Full Text Available Abstract The current pandemic influenza A H1N1 2009 (pH1N1 was first recognized in humans with acute respiratory diseases in April 2009 in Mexico, in swine in Canada in June, 2009 with respiratory disease, and in turkeys in Chile in June 2009 with a severe drop in egg production. Several experimental studies attempted to reproduce the disease in turkeys, but failed to produce respiratory infection in turkeys using standard inoculation routes. We demonstrated that pH1N1 virus can infect the reproductive tract of turkey hens after experimental intrauterine inoculation, causing decreased egg production. This route of exposure is realistic in modern turkey production because turkey hens are handled once a week for intrauterine insemination in order to produce fertile eggs. This understanding of virus exposure provides an improved understanding of the pathogenesis of the disease and can improve poultry husbandry to prevent disease outbreaks.

  10. Full-Genome Sequence of a Reassortant H1N1 Swine Influenza Virus Isolated from Pigs in Italy.

    Science.gov (United States)

    Chiapponi, Chiara; Baioni, Laura; Luppi, Andrea; Moreno, Ana; Castellan, Alberto; Foni, Emanuela

    2013-10-03

    In this study, the full-genome sequence of a novel reassortant H1N1 swine influenza virus (SIV) is reported. The isolate has a hemagglutinin (HA) gene of the pandemic H1N1 influenza virus, but it carries the seven genome segments of the avian-origin H1N1 SIV currently circulating in European pig farms.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  12. Outcomes of influenza A(H1N1)pdm09 virus infection

    DEFF Research Database (Denmark)

    Lynfield, Ruth; Davey, Richard; Dwyer, Dominic E

    2014-01-01

    BACKGROUND: Data from prospectively planned cohort studies on risk of major clinical outcomes and prognostic factors for patients with influenza A(H1N1)pdm09 virus are limited. In 2009, in order to assess outcomes and evaluate risk factors for progression of illness, two cohort studies were...... and/or death for outpatients, and hospitalization for >28 days, transfer to intensive care unit (ICU) if enrolled from general ward, and/or death for inpatients. Infection was confirmed by RT-PCR. 590 FLU 002 and 392 FLU 003 patients with influenza A (H1N1)pdm09 were enrolled from 81 sites in 17...... during the pandemic period had a poorer prognosis than in subsequent seasons. CONCLUSIONS: Patients with influenza A(H1N1)pdm09, particularly when requiring hospital admission, are at high risk for disease progression, especially if they are older, immunodeficient, or admitted late in infection...

  13. Positive Selection on Hemagglutinin and Neuraminidase Genes of H1N1 Influenza Viruses

    LENUS (Irish Health Repository)

    Li, Wenfu

    2011-04-21

    Abstract Background Since its emergence in March 2009, the pandemic 2009 H1N1 influenza A virus has posed a serious threat to public health. To trace the evolutionary path of these new pathogens, we performed a selection-pressure analysis of a large number of hemagglutinin (HA) and neuraminidase (NA) gene sequences of H1N1 influenza viruses from different hosts. Results Phylogenetic analysis revealed that both HA and NA genes have evolved into five distinct clusters, with further analyses indicating that the pandemic 2009 strains have experienced the strongest positive selection. We also found evidence of strong selection acting on the seasonal human H1N1 isolates. However, swine viruses from North America and Eurasia were under weak positive selection, while there was no significant evidence of positive selection acting on the avian isolates. A site-by-site analysis revealed that the positively selected sites were located in both of the cleaved products of HA (HA1 and HA2), as well as NA. In addition, the pandemic 2009 strains were subject to differential selection pressures compared to seasonal human, North American swine and Eurasian swine H1N1 viruses. Conclusions Most of these positively and\\/or differentially selected sites were situated in the B-cell and\\/or T-cell antigenic regions, suggesting that selection at these sites might be responsible for the antigenic variation of the viruses. Moreover, some sites were also associated with glycosylation and receptor-binding ability. Thus, selection at these positions might have helped the pandemic 2009 H1N1 viruses to adapt to the new hosts after they were introduced from pigs to humans. Positive selection on position 274 of NA protein, associated with drug resistance, might account for the prevalence of drug-resistant variants of seasonal human H1N1 influenza viruses, but there was no evidence that positive selection was responsible for the spread of the drug resistance of the pandemic H1N1 strains.

  14. Effect of the novel influenza A (H1N1 virus in the human immune system.

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    Evangelos J Giamarellos-Bourboulis

    Full Text Available BACKGROUND: The pandemic by the novel H1N1 virus has created the need to study any probable effects of that infection in the immune system of the host. METHODOLOGY/PRINCIPAL FINDINGS: Blood was sampled within the first two days of the presentation of signs of infection from 10 healthy volunteers; from 18 cases of flu-like syndrome; and from 31 cases of infection by H1N1 confirmed by reverse RT-PCR. Absolute counts of subtypes of monocytes and of lymphocytes were determined after staining with monoclonal antibodies and analysis by flow cytometry. Peripheral blood mononuclear cells (PBMCs were isolated from patients and stimulated with various bacterial stimuli. Concentrations of tumour necrosis factor-alpha, interleukin (IL-1beta, IL-6, IL-18, interferon (FN-alpha and of IFN-gamma were estimated in supernatants by an enzyme immunoassay. Infection by H1N1 was accompanied by an increase of monocytes. PBMCs of patients evoked strong cytokine production after stimulation with most of bacterial stimuli. Defective cytokine responses were shown in response to stimulation with phytohemagglutin and with heat-killed Streptococcus pneumoniae. Adaptive immune responses of H1N1-infected patients were characterized by decreases of CD4-lymphocytes and of B-lymphocytes and by increase of T-regulatory lymphocytes (Tregs. CONCLUSIONS/SIGNIFICANCE: Infection by the H1N1 virus is accompanied by a characteristic impairment of the innate immune responses characterized by defective cytokine responses to S.pneumoniae. Alterations of the adaptive immune responses are predominated by increase of Tregs. These findings signify a predisposition for pneumococcal infections after infection by H1N1 influenza.

  15. Influenza A viral loads in respiratory samples collected from patients infected with pandemic H1N1, seasonal H1N1 and H3N2 viruses

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    Chuchottaworn Charoen

    2010-04-01

    Full Text Available Abstract Background Nasopharyngeal aspirate (NPA, nasal swab (NS, and throat swab (TS are common specimens used for diagnosis of respiratory virus infections based on the detection of viral genomes, viral antigens and viral isolation. However, there is no documented data regarding the type of specimen that yields the best result of viral detection. In this study, quantitative real time RT-PCR specific for M gene was used to determine influenza A viral loads present in NS, NPA and TS samples collected from patients infected with the 2009 pandemic H1N1, seasonal H1N1 and H3N2 viruses. Various copy numbers of RNA transcripts derived from recombinant plasmids containing complete M gene insert of each virus strain were assayed by RT-PCR. A standard curve for viral RNA quantification was constructed by plotting each Ct value against the log quantity of each standard RNA copy number. Results Copy numbers of M gene were obtained through the extrapolation of Ct values of the test samples against the corresponding standard curve. Among a total of 29 patients with severe influenza enrolled in this study (12 cases of the 2009 pandemic influenza, 5 cases of seasonal H1N1 and 12 cases of seasonal H3N2 virus, NPA was found to contain significantly highest amount of viral loads and followed in order by NS and TS specimen. Viral loads among patients infected with those viruses were comparable regarding type of specimen analyzed. Conclusion Based on M gene copy numbers, we conclude that NPA is the best specimen for detection of influenza A viruses, and followed in order by NS and TS.

  16. Functional Evolution of Influenza Virus NS1 Protein in Currently Circulating Human 2009 Pandemic H1N1 Viruses.

    Science.gov (United States)

    Clark, Amelia M; Nogales, Aitor; Martinez-Sobrido, Luis; Topham, David J; DeDiego, Marta L

    2017-09-01

    In 2009, a novel H1N1 influenza virus emerged in humans, causing a global pandemic. It was previously shown that the NS1 protein from this human 2009 pandemic H1N1 (pH1N1) virus was an effective interferon (IFN) antagonist but could not inhibit general host gene expression, unlike other NS1 proteins from seasonal human H1N1 and H3N2 viruses. Here we show that the NS1 protein from currently circulating pH1N1 viruses has evolved to encode 6 amino acid changes (E55K, L90I, I123V, E125D, K131E, and N205S) with respect to the original protein. Notably, these 6 residue changes restore the ability of pH1N1 NS1 to inhibit general host gene expression, mainly by their ability to restore binding to the cellular factor CPSF30. This is the first report describing the ability of the pH1N1 NS1 protein to naturally acquire mutations that restore this function. Importantly, a recombinant pH1N1 virus containing these 6 amino acid changes in the NS1 protein (pH1N1/NSs-6mut) inhibited host IFN and proinflammatory responses to a greater extent than that with the parental virus (pH1N1/NS1-wt), yet virus titers were not significantly increased in cell cultures or in mouse lungs, and the disease was partially attenuated. The pH1N1/NSs-6mut virus grew similarly to pH1N1/NSs-wt in mouse lungs, but infection with pH1N1/NSs-6mut induced lower levels of proinflammatory cytokines, likely due to a general inhibition of gene expression mediated by the mutated NS1 protein. This lower level of inflammation induced by the pH1N1/NSs-6mut virus likely accounts for the attenuated disease phenotype and may represent a host-virus adaptation affecting influenza virus pathogenesis.IMPORTANCE Seasonal influenza A viruses (IAVs) are among the most common causes of respiratory infections in humans. In addition, occasional pandemics are caused when IAVs circulating in other species emerge in the human population. In 2009, a swine-origin H1N1 IAV (pH1N1) was transmitted to humans, infecting people then and up

  17. Genetic characterization of the influenza A pandemic (H1N1 2009 virus isolates from India.

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    Varsha A Potdar

    Full Text Available BACKGROUND: The Influenza A pandemic H1N1 2009 (H1N1pdm virus appeared in India in May 2009 and thereafter outbreaks with considerable morbidity and mortality have been reported from many parts of the country. Continuous monitoring of the genetic makeup of the virus is essential to understand its evolution within the country in relation to global diversification and to track the mutations that may affect the behavior of the virus. METHODS: H1N1pdm viruses were isolated from both recovered and fatal cases representing major cities and sequenced. Phylogenetic analyses of six concatenated whole genomes and the hemagglutinin (HA gene of seven more isolates from May-September 2009 was performed with reference to 685 whole genomes of global isolates available as of November 24, 2009. Molecular characterization of all the 8 segments was carried out for known pathogenic markers. RESULTS: The first isolate of May 2009 belonged to clade 5. Although clade 7 was the dominant H1N1pdm lineage in India, both clades 6 and 7 were found to be co-circulating. The neuraminidase of all the Indian isolates possessed H275, the marker for sensitivity to the neuraminidase inhibitor Oseltamivir. Some of the mutations in HA are at or in the vicinity of antigenic sites and may therefore be of possible antigenic significance. Among these a D222G mutation in the HA receptor binding domain was found in two of the eight Indian isolates obtained from fatal cases. CONCLUSIONS: The majority of the 13 Indian isolates grouped in the globally most widely circulating H1N1pdm clade 7. Further, correlations of the mutations specific to clade 7 Indian isolates to viral fitness and adaptability in the country remains to be understood. The D222G mutation in HA from isolates of fatal cases needs to be studied for pathogenicity.

  18. Replication, Pathogenesis and Transmission of Pandemic (H1N1) 2009 Virus in Non-Immune Pigs

    NARCIS (Netherlands)

    Brookes, S.M.; Nunez, A.; Choudhury, B.; Matrosovich, M.; Essen, S.C.; Clifford, D.; Slomka, M.J.; Kuntz-Simon, G.; Garcon, F.; Nash, B.; Hanna, A.; Heegaard, P.M.H.; Queguiner, S.; Chiapponi, C.; Bublot, M.; Garcia, J.M.; Gardner, R.; Foni, E.; Loeffen, W.L.A.; Larsen, L.; Reeth, K.; Banks, J.; Irvine, R.M.; Brown, I.H.

    2010-01-01

    The declaration of the human influenza A pandemic (H1N1) 2009 (H1N1/09) raised important questions, including origin and host range [1,2]. Two of the three pandemics in the last century resulted in the spread of virus to pigs (H1N1, 1918; H3N2, 1968) with subsequent independent establishment and evo

  19. Replication, Pathogenesis and Transmission of Pandemic (H1N1) 2009 Virus in Non-Immune Pigs

    DEFF Research Database (Denmark)

    Brookes, Sharon M; Nunez, Alejandor; Choudhury, Bhudipa

    2010-01-01

    The declaration of the human influenza A pandemic (H1N1) 2009 (H1N1/09) raised important questions, including origin and host range [1,2]. Two of the three pandemics in the last century resulted in the spread of virus to pigs (H1N1, 1918; H3N2, 1968) with subsequent independent establishment...

  20. Persistence of the 2009 pandemic influenza A (H1N1) virus on N95 respirators.

    Science.gov (United States)

    Coulliette, A D; Perry, K A; Edwards, J R; Noble-Wang, J A

    2013-04-01

    In the United States, the 2009 pandemic influenza A (H1N1) virus (pH1N1) infected almost 20% of the population and caused >200,000 hospitalizations and >10,000 deaths from April 2009 to April 2010. On 24 April 2009, the CDC posted interim guidance on infection control measures in health care settings explicitly for pH1N1 and recommended using filtering face respirators (FFRs) when in close contact with a suspected- or confirmed-to-be-infected individual, particularly when performing aerosol-generating procedures. The persistence and infectivity of pH1N1 were evaluated on FFRs, specifically N95 respirators, under various conditions of absolute humidity (AH) (4.1 × 10(5) mPa, 6.5 × 10(5) mPa, and 14.6 × 10(5) mPa), sample matrices (2% fetal bovine serum [FBS], 5 mg/ml mucin, and viral medium), and times (4, 12, 24, 48, 72, and 144 h). pH1N1 was distributed onto N95 coupons (3.8 to 4.2 cm(2)) and extracted by a vortex-centrifugation-filtration process, and the ability of the remaining virus to replicate was quantified using an enzyme-linked immunosorbent assay (ELISA) to determine the log10 concentration of the infectious virus per coupon. Overall, pH1N1 remained infectious for 6 days, with an approximately 1-log10 loss of virus concentrations over this time period. Time and AH both affected virus survival. We found significantly higher (P ≤ 0.01) reductions in virus concentrations at time points beyond 24 to 72 h (-0.52-log10 reduction) and 144 h (-0.74) at AHs of 6.5 × 10(5) mPa (-0.53) and 14.6 × 10(5) mPa (-0.47). This research supports discarding respirators after close contact with a person with suspected or confirmed influenza infection due to the virus's demonstrated ability to persist and remain infectious.

  1. Prediction of biological functions on glycosylation site migrations in human influenza H1N1 viruses.

    Science.gov (United States)

    Sun, Shisheng; Wang, Qinzhe; Zhao, Fei; Chen, Wentian; Li, Zheng

    2012-01-01

    Protein glycosylation alteration is typically employed by various viruses for escaping immune pressures from their hosts. Our previous work had shown that not only the increase of glycosylation sites (glycosites) numbers, but also glycosite migration might be involved in the evolution of human seasonal influenza H1N1 viruses. More importantly, glycosite migration was likely a more effectively alteration way for the host adaption of human influenza H1N1 viruses. In this study, we provided more bioinformatics and statistic evidences for further predicting the significant biological functions of glycosite migration in the host adaptation of human influenza H1N1 viruses, by employing homology modeling and in silico protein glycosylation of representative HA and NA proteins as well as amino acid variability analysis at antigenic sites of HA and NA. The results showed that glycosite migrations in human influenza viruses have at least five possible functions: to more effectively mask the antigenic sites, to more effectively protect the enzymatic cleavage sites of neuraminidase (NA), to stabilize the polymeric structures, to regulate the receptor binding and catalytic activities and to balance the binding activity of hemagglutinin (HA) with the release activity of NA. The information here can provide some constructive suggestions for the function research related to protein glycosylation of influenza viruses, although these predictions still need to be supported by experimental data.

  2. Transmission of Pandemic Influenza A (H1N1) Virus in a Train in China

    Science.gov (United States)

    Cui, Fuqiang; Luo, Huiming; Zhou, Lei; Yin, Dapeng; Zheng, Canjun; Wang, Dingming; Gong, Jian; Fang, Gang; He, Jianfeng; McFarland, Jeffrey; Yu, Hongjie

    2011-01-01

    Background Pandemic influenza A (H1N1) virus emerged in North America in April 2009 and spread globally. We describe the epidemiology and public health response to the first known outbreak of 2009 H1N1 in a train, which occurred in June 2009 in China. Methods After 2 provinces provided initial reports of 2009 H1N1 infection in 2 persons who had travelled on the same train, we conducted a retrospective epidemiologic investigation to collect information from the passengers, crew members, contacts, and health care providers. We explored the source of infection and possible routes of transmission in the train. All cases were confirmed by real-time reverse transcription polymerase chain reaction testing. Results Train #1223 traveled 40 hours, made 28 stops in 4 Chinese provinces, and boarded 2555 passengers, who logged a total of 59 144 person-hours of travel time. Nineteen confirmed 2009 H1N1 cases were identified. Of these, 13 were infected and developed symptoms on the train and 6 occurred among contacts who developed illness during medical monitoring. In addition, 3 asymptomatic cases were identified based on RT-PCR testing of respiratory swabs from contacts. The attack rate among contacts of confirmed cases in the same car was higher than that among contacts in other cars (3.15% vs. 0%, P train. Trains may have played an important role in the 2009 influenza pandemic. PMID:21646746

  3. Designing inhibitors of M2 proton channel against H1N1 swine influenza virus.

    Directory of Open Access Journals (Sweden)

    Qi-Shi Du

    Full Text Available BACKGROUND: M2 proton channel of H1N1 influenza A virus is the target protein of anti-flu drugs amantadine and rimantadine. However, the two once powerful adamantane-based drugs lost their 90% bioactivity because of mutations of virus in recent twenty years. The NMR structure of the M2 channel protein determined by Schnell and Chou (Nature, 2008, 451, 591-595 may help people to solve the drug-resistant problem and develop more powerful new drugs against H1N1 influenza virus. METHODOLOGY: Docking calculation is performed to build the complex structure between receptor M2 proton channel and ligands, including existing drugs amantadine and rimantadine, and two newly designed inhibitors. The computer-aided drug design methods are used to calculate the binding free energies, with the computational biology techniques to analyze the interactions between M2 proton channel and adamantine-based inhibitors. CONCLUSIONS: 1 The NMR structure of M2 proton channel provides a reliable structural basis for rational drug design against influenza virus. 2 The channel gating mechanism and the inhibiting mechanism of M2 proton channel, revealed by the NMR structure of M2 proton channel, provides the new ideas for channel inhibitor design. 3 The newly designed adamantane-based inhibitors based on the modeled structure of H1N1-M2 proton channel have two pharmacophore groups, which act like a "barrel hoop", holding two adjacent helices of the H1N1-M2 tetramer through the two pharmacophore groups outside the channel. 4 The inhibitors with such binding mechanism may overcome the drug resistance problem of influenza A virus to the adamantane-based drugs.

  4. Molecular epidemiology study of swine influenza virus revealing a reassorted virus H1N1 in swine farms in Cuba.

    Science.gov (United States)

    Pérez, Lester J; Perera, Carmen Laura; Coronado, Liani; Rios, Liliam; Vega, Armando; Frías, Maria T; Ganges, Llilianne; Núñez, José Ignacio; Díaz de Arce, Heidy

    2015-05-01

    In this report, we describe the emergence of reassorted H1N1 swine influenza virus, originated from a reassortment event between the H1N1 pandemic influenza virus (H1N1p/2009) and endemic swine influenza virus in Cuban swine population. In November 2010, a clinical respiratory outbreak was reported on a pig fattening farm in Cuba. Phylogenetic analysis showed that all the genes of one of the isolate obtained, with the exception of neuraminidase, belonged to the H1N1p/2009 cluster. This finding suggests that H1N1pdm has been established in swine and has become a reservoir of reassortment that may produce new viruses with both animal and public health risks.

  5. Neutralization and Binding Profile of Monoclonal Antibodies Generated Against Influenza A H1N1 Viruses.

    Science.gov (United States)

    Shembekar, Nachiket; Mallajosyula, Vamsee V Aditya; Malik, Ankita; Saini, Ashok; Varadarajan, Raghavan; Gupta, Satish Kumar

    2016-08-01

    Monoclonal antibodies (MAbs) provide scope for the development of better therapeutics and diagnostic tools. Herein, we describe the binding and neutralization profile(s) for a panel of murine MAbs generated against influenza A H1N1 viruses elicited by immunization with pandemic H1 recombinant hemagglutinin (rHA)/whole virus or seasonal H1 rHA. Neutralizing MAbs, MA-2070 and MA-M, were obtained after pandemic A/California/07/2009 (H1N1) virus/rHA immunization(s). Both MAbs reacted specifically with rHA from A/California/07/2009 and A/England/195/2009 in ELISA. MA-2070 bound rHA of A/California/07/2009 with high affinity (KD = 51.36 ± 9.20 nM) and exhibited potent in vitro neutralization (IC50 = 2.50 μg/mL). MA-2070 bound within the stem domain of HA. MA-M exhibited both hemagglutination inhibition (HI, 1.50 μg/mL) and in vitro neutralization (IC50 = 0.66 μg/mL) activity against the pandemic A/California/07/2009 virus and showed higher binding affinity (KD = 9.80 ± 0.67 nM) than MA-2070. MAb, MA-H generated against the seasonal A/Solomon Islands/03/2006 (H1N1) rHA binds within the head domain and bound the seasonal H1N1 (A/Solomon Islands/03/2006 and A/New Caledonia/20/1990) rHAs with high affinity (KD; 0.72-8.23 nM). MA-H showed high HI (2.50 μg/mL) and in vitro neutralization (IC50 = 2.61 μg/mL) activity against the A/Solomon Islands/03/2006 virus. All 3 MAbs failed to react in ELISA with rHA from various strains of H2N2, H3N2, H5N1, H7N9, and influenza virus B, suggesting their specificity for either pandemic or seasonal H1N1 influenza virus. The MAbs reported here may be useful in developing diagnostic assays.

  6. The pandemic (H1N1 2009 influenza virus is resistant to mannose-binding lectin

    Directory of Open Access Journals (Sweden)

    Ushirogawa Hiroshi

    2011-02-01

    Full Text Available Abstract Background Mannose-binding lectin (MBL is an important component of innate immunity because it promotes bacterial clearance and neutralization of human influenza A viruses. Since a majority of humans have no neutralizing antibody against the pandemic (H1N1 2009 influenza (pandemic 2009 virus, innate immunity may be crucial and MBL susceptibility may therefore influence viral pathogenesis. Results We examined MBL susceptibility of influenza A viruses and observed that the pandemic 2009 virus was resistant to MBL, whereas all seasonal influenza A viruses tested were susceptible. The mortality of mice infected with a seasonal H1N1 influenza virus was evidently enhanced on transient blockage of MBL activity by simultaneous inoculation of mannan, whereas mannan inoculation had no effect on mice infected with a pandemic 2009 virus. This indicates that MBL protects mice against infection with the seasonal virus but not against that with the pandemic 2009 virus. Conclusions These results indicate that the pandemic 2009 virus is not susceptible to MBL, an important component of innate immunity.

  7. H7N9 Influenza Virus Is More Virulent in Ferrets than 2009 Pandemic H1N1 Influenza Virus.

    Science.gov (United States)

    Yum, Jung; Ku, Keun Bon; Kim, Hyun Soo; Seo, Sang Heui

    2015-12-01

    The novel H7N9 influenza virus has been infecting humans in China since February 2013 and with a mortality rate of about 40%. This study compared the pathogenicity of the H7N9 and 2009 pandemic H1N1 influenza viruses in a ferret model, which shows similar symptoms to those of humans infected with influenza viruses. The H7N9 influenza virus caused a more severe disease than did the 2009 pandemic H1N1 influenza virus. All of the ferrets infected with the H7N9 influenza virus had died by 6 days after infection, while none of those infected with the 2009 pandemic H1N1 influenza virus died. Ferrets infected with the H7N9 influenza virus had higher viral titers in their lungs than did those infected with the 2009 pandemic H1N1 influenza virus. Histological findings indicated that hemorrhagic pneumonia was caused by infection with the H7N9 influenza virus, but not with the 2009 pandemic H1N1 influenza virus. In addition, the lung tissues of ferrets infected with the H7N9 influenza virus contained higher levels of chemokines than did those of ferrets infected with the 2009 pandemic H1N1 influenza virus. This study suggests that close monitoring is needed to prevent human infection by the lethal H7N9 influenza virus.

  8. Molecular characterization of H1N1 influenza A viruses from human cases in North America

    Institute of Scientific and Technical Information of China (English)

    WU Bin; WANG ChengMin; DONG GuoYing; LUO Jing; ZHAO BaoHua; HE HongXuan

    2009-01-01

    Subtypes of H1N1 influenza virus can be found in humans in North America,while they are also associated with the infection of swine.Characterization of the genotypes of viral strains in human populations is important to understand the source and distribution of viral strains.Genomic and protein sequences of 10 isolates of the 2009 outbreak of influenza A (H1N1) virus in North America were obtained from GenBank database.To characterize the genotypes of these viruses,phylogenetic trees of genes PB2,PB1,PA,HA,NP,NA,NS and M were constructed by Phylip3.67 program and N-Linked glycosylation sites of HA,NA,PB2,NS1 and M2 proteins were analyzed online by NetNGIyc1.0 program.Phylogenetic analysis indicated that these isolates are virtually identical but may be recombinant viruses because their genomic fragments come from different viruses.The isolates also contain a characteristic lowly pathogenic amino acid motif at their HA cleavage sites (IPSIQSR↓GL),and an E residue at position 627 of the PB2 protein which shows its high affinity to humans.The homologous model of M proteins showed that the viruses had obtained the ability of anti-amantadine due to the mutation at the drug-sensitive site,while sequence analysis of NA proteins indicated that the viruses are still susceptible to the neuraminidase inhibitor drug (i.e.oseltamivir and zanamivir) because no mutations have been observed.Our results strongly suggested that the viruses responsible for the 2009 outbreaks of influenza A (H1N1) virus have the ability to cross species barriers to infect human and mammalian animals based on molecular analysis.These findings may further facilitate the therapy and prevention of possible transmission from North America to other countries.

  9. Novel Influenza A (H1N1) Virus Infection in Children: Chest Radiographic and CT Evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Min Jeong; Lee, Young Seok; Lee, Jee Young; Lee, Kun Song [Dankook University College of Medicine, Dankook University Hospital, Cheonan (Korea, Republic of)

    2010-12-15

    The purpose of this study was to evaluate the chest radiographic and CT findings of novel influenza A (H1N1) virus infection in children, the population that is more vulnerable to respiratory infection than adults. The study population comprised 410 children who were diagnosed with an H1N1 infection from August 24, 2009 to November 11, 2009 and underwent chest radiography at Dankook University Hospital in Korea. Six of these patients also underwent chest CT. The initial chest radiographs were classified as normal or abnormal. The abnormal chest radiographs and high resolution CT scans were assessed for the pattern and distribution of parenchymal lesions, and the presence of complications such as atelectasis, pleural effusion, and pneumomediastinum. The initial chest radiograph was normal in 384 of 410 (94%) patients and abnormal in 26 of 410 (6%) patients. Parenchymal abnormalities seen on the initial chest radiographs included prominent peribronchial marking (25 of 26, 96%), consolidation (22 of 26, 85%), and ground-glass opacities without consolidation (2 of 26, 8%). The involvement was usually bilateral (19 of 26, 73%) with the lower lung zone predominance (22 of 26, 85%). Atelectasis was observed in 12 (46%) and pleural effusion in 11 (42%) patients. CT (n = 6) scans showed peribronchovascular interstitial thickening (n = 6), ground-glass opacities (n = 5), centrilobular nodules (n = 4), consolidation (n = 3), mediastinal lymph node enlargement (n = 5), pleural effusion (n = 3), and pneumomediastinum (n = 3). Abnormal chest radiographs were uncommon in children with a swine-origin influenza A (H1N1) virus (S-OIV) infection. In children, H1N1 virus infection can be included in the differential diagnosis, when chest radiographs and CT scans show prominent peribronchial markings and ill-defined patchy consolidation with mediastinal lymph node enlargement, pleural effusion and pneumomediastinum

  10. Oseltamivir-resistant influenza A(H1N1pdm09 virus in southern Brazil

    Directory of Open Access Journals (Sweden)

    Camila Marx

    2013-05-01

    Full Text Available The neuraminidase (NA genes of A(H1N1pdm09 influenza virus isolates from 306 infected patients were analysed. The circulation of oseltamivir-resistant viruses in Brazil has not been reported previously. Clinical samples were collected in the state of Rio Grande do Sul (RS from 2009-2011 and two NA inhibitor-resistant mutants were identified, one in 2009 (H275Y and the other in 2011 (S247N. This study revealed a low prevalence of resistant viruses (0.8% with no spread of the resistant mutants throughout RS.

  11. Outcomes of influenza A(H1N1)pdm09 virus infection

    DEFF Research Database (Denmark)

    Lynfield, Ruth; Davey, Richard; Dwyer, Dominic E

    2014-01-01

    BACKGROUND: Data from prospectively planned cohort studies on risk of major clinical outcomes and prognostic factors for patients with influenza A(H1N1)pdm09 virus are limited. In 2009, in order to assess outcomes and evaluate risk factors for progression of illness, two cohort studies were...... initiated: FLU 002 in outpatients and FLU 003 in hospitalized patients. METHODS AND FINDINGS: Between October 2009 and December 2012, adults with influenza-like illness (ILI) were enrolled; outpatients were followed for 14 days and inpatients for 60 days. Disease progression was defined as hospitalization...... and/or death for outpatients, and hospitalization for >28 days, transfer to intensive care unit (ICU) if enrolled from general ward, and/or death for inpatients. Infection was confirmed by RT-PCR. 590 FLU 002 and 392 FLU 003 patients with influenza A (H1N1)pdm09 were enrolled from 81 sites in 17...

  12. The Genomic Contributions of Avian H1N1 Influenza A Viruses to the Evolution of Mammalian Strains.

    Science.gov (United States)

    Koçer, Zeynep A; Carter, Robert; Wu, Gang; Zhang, Jinghui; Webster, Robert G

    2015-01-01

    Among the influenza A viruses (IAVs) in wild aquatic birds, only H1, H2, and H3 subtypes have caused epidemics in humans. H1N1 viruses of avian origin have also caused 3 of 5 pandemics. To understand the reappearance of H1N1 in the context of pandemic emergence, we investigated whether avian H1N1 IAVs have contributed to the evolution of human, swine, and 2009 pandemic H1N1 IAVs. On the basis of phylogenetic analysis, we concluded that the polymerase gene segments (especially PB2 and PA) circulating in North American avian H1N1 IAVs have been reintroduced to swine multiple times, resulting in different lineages that led to the emergence of the 2009 pandemic H1N1 IAVs. Moreover, the similar topologies of hemagglutinin and nucleoprotein and neuraminidase and matrix gene segments suggest that each surface glycoprotein coevolved with an internal gene segment within the H1N1 subtype. The genotype of avian H1N1 IAVs of Charadriiformes origin isolated in 2009 differs from that of avian H1N1 IAVs of Anseriformes origin. When the antigenic sites in the hemagglutinin of all 31 North American avian H1N1 IAVs were considered, 60%-80% of the amino acids at the antigenic sites were identical to those in 1918 and/or 2009 pandemic H1N1 viruses. Thus, although the pathogenicity of avian H1N1 IAVs could not be inferred from the phylogeny due to the small dataset, the evolutionary process within the H1N1 IAV subtype suggests that the circulation of H1N1 IAVs in wild birds poses a continuous threat for future influenza pandemics in humans.

  13. Novel triple-reassortant H1N1 swine influenza viruses in pigs in Tianjin, Northern China.

    Science.gov (United States)

    Sun, Ying-Feng; Wang, Xiu-Hui; Li, Xiu-Li; Zhang, Li; Li, Hai-Hua; Lu, Chao; Yang, Chun-Lei; Feng, Jing; Han, Wei; Ren, Wei-Ke; Tian, Xiang-Xue; Tong, Guang-Zhi; Wen, Feng; Li, Ze-Jun; Gong, Xiao-Qian; Liu, Xiao-Min; Ruan, Bao-Yang; Yan, Ming-Hua; Yu, Hai

    2016-02-01

    Pigs are susceptible to both human and avian influenza viruses and therefore have been proposed to be mixing vessels for the generation of pandemic influenza viruses through reassortment. In this study, for the first time, we report the isolation and genetic analyses of three novel triple-reassortant H1N1 swine influenza viruses from pigs in Tianjin, Northern China. Phylogenetic analysis showed that these novel viruses contained genes from the 2009 pandemic H1N1 (PB2, PB1, PA and NP), Eurasian swine (HA, NA and M) and triple-reassortant swine (NS) lineages. This indicated that the reassortment among the 2009 pandemic H1N1, Eurasian swine and triple-reassortant swine influenza viruses had taken place in pigs in Tianjin and resulted in the generation of new viruses. Furthermore, three human-like H1N1, two classical swine H1N1 and two Eurasian swine H1N1 viruses were also isolated during the swine influenza virus surveillance from 2009 to 2013, which indicated that multiple genetic lineages of swine H1N1 viruses were co-circulating in the swine population in Tianjin, China. The emergence of novel triple-reassortant H1N1 swine influenza viruses may be a potential threat to human health and emphasizes the importance of further continuous surveillance.

  14. Possible basis for the emergence of H1N1 viruses with pandemic potential from avian hosts.

    Science.gov (United States)

    Koçer, Zeynep A; Krauss, Scott; Zanin, Mark; Danner, Angela; Gulati, Shelly; Jones, Jeremy C; Friedman, Kimberly; Graham, Allison; Forrest, Heather; Seiler, Jon; Air, Gillian M; Webster, Robert G

    2015-07-01

    Influenza A viruses of the H1N1 subtype have emerged from the avian influenza gene pool in aquatic birds and caused human pandemics at least twice during the past century. Despite this fact, surprisingly little is known about the H1N1 gene pool in the aquatic bird reservoir. A preliminary study showed that an H1N1 virus from a shorebird of the Charadriiformes order was transmitted between animals through the airborne route of infection, whereas an H1N1 virus from a bird of the Anseriformes order was not. Here we show that two of the three H1N1 viruses isolated from Charadriiformes species in 2009 were transmitted between animals through the airborne route of infection, and five H1N1 isolates from Anseriformes species were not. The one H1N1 virus from a Charadriiformes species that failed to transmit through the airborne route was a reassortant possessing multiple internal gene segments from Anseriformes species. The molecular differences between the airborne-transmissible and non-airborne-transmissible H1N1 viruses were multigenic, involving the selection of virus with human-like receptor-binding specificity (α2-6 sialic acid) and multiple differences in the polymerase complex, mainly in the PB2, PB1-F2, and nonstructural genes.

  15. Caveolin-1 influences human influenza A virus (H1N1 multiplication in cell culture

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    Hemgård Gun-Viol

    2010-05-01

    Full Text Available Abstract Background The threat of recurring influenza pandemics caused by new viral strains and the occurrence of escape mutants necessitate the search for potent therapeutic targets. The dependence of viruses on cellular factors provides a weak-spot in the viral multiplication strategy and a means to interfere with viral multiplication. Results Using a motif-based search strategy for antiviral targets we identified caveolin-1 (Cav-1 as a putative cellular interaction partner of human influenza A viruses, including the pandemic influenza A virus (H1N1 strains of swine origin circulating from spring 2009 on. The influence of Cav-1 on human influenza A/PR/8/34 (H1N1 virus replication was determined in inhibition and competition experiments. RNAi-mediated Cav-1 knock-down as well as transfection of a dominant-negative Cav-1 mutant results in a decrease in virus titre in infected Madin-Darby canine kidney cells (MDCK, a cell line commonly used in basic influenza research as well as in virus vaccine production. To understand the molecular basis of the phenomenon we focussed on the putative caveolin-1 binding domain (CBD located in the lumenal, juxtamembranal portion of the M2 matrix protein which has been identified in the motif-based search. Pull-down assays and co-immunoprecipitation experiments showed that caveolin-1 binds to M2. The data suggest, that Cav-1 modulates influenza virus A replication presumably based on M2/Cav-1 interaction. Conclusion As Cav-1 is involved in the human influenza A virus life cycle, the multifunctional protein and its interaction with M2 protein of human influenza A viruses represent a promising starting point for the search for antiviral agents.

  16. Antiviral activity of silver nanoparticle/chitosan composites against H1N1 influenza A virus

    Science.gov (United States)

    Mori, Yasutaka; Ono, Takeshi; Miyahira, Yasushi; Nguyen, Vinh Quang; Matsui, Takemi; Ishihara, Masayuki

    2013-02-01

    Silver nanoparticle (Ag NP)/chitosan (Ch) composites with antiviral activity against H1N1 influenza A virus were prepared. The Ag NP/Ch composites were obtained as yellow or brown floc-like powders following reaction at room temperature in aqueous medium. Ag NPs (3.5, 6.5, and 12.9 nm average diameters) were embedded into the chitosan matrix without aggregation or size alternation. The antiviral activity of the Ag NP/Ch composites was evaluated by comparing the TCID50 ratio of viral suspensions treated with the composites to untreated suspensions. For all sizes of Ag NPs tested, antiviral activity against H1N1 influenza A virus increased as the concentration of Ag NPs increased; chitosan alone exhibited no antiviral activity. Size dependence of the Ag NPs on antiviral activity was also observed: antiviral activity was generally stronger with smaller Ag NPs in the composites. These results indicate that Ag NP/Ch composites interacting with viruses exhibit antiviral activity.

  17. Heterogeneous virulence of pandemic 2009 influenza H1N1 virus in mice

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    Farooqui Amber

    2012-06-01

    Full Text Available Abstract Background Understanding the pathogenesis of influenza infection is a key factor leading to the prevention and control of future outbreaks. Pandemic 2009 Influenza H1N1 infection, although frequently mild, led to a severe and fatal form of disease in certain cases that make its virulence nature debatable. Much effort has been made toward explaining the determinants of disease severity; however, no absolute reason has been established. Results This study presents the heterogeneous virulence of clinically similar strains of pandemic 2009 influenza virus in human alveolar adenocarcinoma cells and mice. The viruses were obtained from patients who were admitted in a local hospital in China with a similar course of infection and recovered. The A/Nanchang/8002/2009 and A/Nanchang/8011/2009 viruses showed efficient replication and high lethality in mice while infection with A/Nanchang/8008/2009 was not lethal with impaired viral replication, minimal pathology and modest proinflammatory activity in lungs. Sequence analysis displayed prominent differences between polymerase subunits (PB2 and PA of viral genomes that might correlate with their different phenotypic behavior. Conclusions The study confirms that biological heterogeneity, linked with the extent of viral replication, exists among pandemic H1N1 strains that may serve as a benchmark for future investigations on influenza pathogenesis.

  18. Modified vaccinia virus Ankara expressing the hemagglutinin of pandemic (H1N1) 2009 virus induces cross-protective immunity against Eurasian 'avian-like' H1N1 swine viruses in mice.

    Science.gov (United States)

    Castrucci, Maria R; Facchini, Marzia; Di Mario, Giuseppina; Garulli, Bruno; Sciaraffia, Ester; Meola, Monica; Fabiani, Concetta; De Marco, Maria A; Cordioli, Paolo; Siccardi, Antonio; Kawaoka, Yoshihiro; Donatelli, Isabella

    2014-05-01

    To examine cross-reactivity between hemagglutinin (HA) derived from A/California/7/09 (CA/09) virus and that derived from representative Eurasian "avian-like" (EA) H1N1 swine viruses isolated in Italy between 1999 and 2008 during virological surveillance in pigs. Modified vaccinia virus Ankara (MVA) expressing the HA gene of CA/09 virus (MVA-HA-CA/09) was used as a vaccine to investigate cross-protective immunity against H1N1 swine viruses in mice. Two classical swine H1N1 (CS) viruses and four representative EA-like H1N1 swine viruses previously isolated during outbreaks of respiratory disease in pigs on farms in Northern Italy were used in this study. Female C57BL/6 mice were vaccinated with MVA/HA/CA/09 and then challenged intranasally with H1N1 swine viruses. Cross-reactive antibody responses were determined by hemagglutination- inhibition (HI) and virus microneutralizing (MN) assays of sera from MVA-vaccinated mice. The extent of protective immunity against infection with H1N1 swine viruses was determined by measuring lung viral load on days 2 and 4 post-challenge. Systemic immunization of mice with CA/09-derived HA, vectored by MVA, elicited cross-protective immunity against recent EA-like swine viruses. This immune protection was related to the levels of cross-reactive HI antibodies in the sera of the immunized mice and was dependent on the similarity of the antigenic site Sa of H1 HAs. Our findings suggest that the herd immunity elicited in humans by the pandemic (H1N1) 2009 virus could limit the transmission of recent EA-like swine HA genes into the influenza A virus gene pool in humans. © 2013 The Authors Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

  19. Update: novel influenza A (H1N1) virus infection - Mexico, March-May, 2009.

    Science.gov (United States)

    2009-06-05

    On April 12, 2009, Mexico responded to a request for verification by the World Health Organization (WHO) of an outbreak of acute respiratory illness in the small community of La Gloria, Veracruz. During April 15-17, the Mexico Ministry of Health received informal notification of clusters of rapidly progressive severe pneumonia occurring mostly in Distrito Federal (metropolitan Mexico City) and San Luis Potosi. In response, on April 17, Mexico intensified national surveillance for acute respiratory illness and pneumonia. During April 22-24, novel influenza A (H1N1) virus infection, previously identified in two children in the United States, was confirmed in several patients. This report updates a previous report on the outbreak in Mexico and summarizes public health actions taken to date by Mexico to monitor and control the outbreak. During March 1-May 29, national surveillance identified 41,998 persons with acute respiratory illness; specimens from 25,127 (59.8%) patients were tested, of which 5,337 (21.2%) were positive for novel influenza A (H1N1) virus infection by real-time reverse transcription--polymerase chain reaction (rRT-PCR). As of May 29, 97 patients with laboratory-confirmed infection had died. Epidemiologic evidence to date suggests that the outbreak likely peaked nationally in late April, although localized cases continue to be identified.

  20. Human Dendritic Cell Response Signatures Distinguish 1918, Pandemic, and Seasonal H1N1 Influenza Viruses.

    Science.gov (United States)

    Hartmann, Boris M; Thakar, Juilee; Albrecht, Randy A; Avey, Stefan; Zaslavsky, Elena; Marjanovic, Nada; Chikina, Maria; Fribourg, Miguel; Hayot, Fernand; Schmolke, Mirco; Meng, Hailong; Wetmur, James; García-Sastre, Adolfo; Kleinstein, Steven H; Sealfon, Stuart C

    2015-10-01

    Influenza viruses continue to present global threats to human health. Antigenic drift and shift, genetic reassortment, and cross-species transmission generate new strains with differences in epidemiology and clinical severity. We compared the temporal transcriptional responses of human dendritic cells (DC) to infection with two pandemic (A/Brevig Mission/1/1918, A/California/4/2009) and two seasonal (A/New Caledonia/20/1999, A/Texas/36/1991) H1N1 influenza viruses. Strain-specific response differences included stronger activation of NF-κB following infection with A/New Caledonia/20/1999 and a unique cluster of genes expressed following infection with A/Brevig Mission/1/1918. A common antiviral program showing strain-specific timing was identified in the early DC response and found to correspond with reported transcript changes in blood during symptomatic human influenza virus infection. Comparison of the global responses to the seasonal and pandemic strains showed that a dramatic divergence occurred after 4 h, with only the seasonal strains inducing widespread mRNA loss. Continuously evolving influenza viruses present a global threat to human health; however, these host responses display strain-dependent differences that are incompletely understood. Thus, we conducted a detailed comparative study assessing the immune responses of human DC to infection with two pandemic and two seasonal H1N1 influenza strains. We identified in the immune response to viral infection both common and strain-specific features. Among the stain-specific elements were a time shift of the interferon-stimulated gene response, selective induction of NF-κB signaling by one of the seasonal strains, and massive RNA degradation as early as 4 h postinfection by the seasonal, but not the pandemic, viruses. These findings illuminate new aspects of the distinct differences in the immune responses to pandemic and seasonal influenza viruses. Copyright © 2015, American Society for Microbiology. All

  1. Pandemic H1N1 2009 virus in Norwegian pigs naïve to influenza A viruses

    DEFF Research Database (Denmark)

    Germundsson, A.; Gjerset, B.; Hjulsager, Charlotte Kristiane

    In March-April 2009, a novel pandemic influenza A (H1N1) virus (pH1N1-09v) emerged in the human population. The first case of pH1N1v infection in pigs was reported from Canada in May 2009. In Norway, pH1N1v infection was recorded in a swine herd on the 10th of October of 2009. Here, we report...... showed clinical signs or iii) with a history of close contact with or close proximity to infected herds. In addition, blood samples were collected from nucleus and multiplier breeding herds. Detection of pH1N1-09v was initially performed using a real-time RT-PCR targeted to detect influenza A virus....... Positive samples were tested by a pH1N1-09v specific real-time RT-PCR. Blood samples were tested for presence of antibodies against influenza A virus by ELISA (IDVET) and positive samples in the ELISA were tested by haemagglutinin inhibition test using A/California/07/09 as antigen. From the onset...

  2. Homology modelling and insilico analysis of neuraminidase protein in H1N1 Influenza A virus

    Directory of Open Access Journals (Sweden)

    Abhilash Manohar

    2011-02-01

    Full Text Available In this work, modelling of Neuraminidase protein of Influenza A virus (A/Himeji/1/2009(H1N1 neuraminidase (NA protein was done using Modeller 9V2. Modelled structure was submitted to protein model database and could be downloaded using accession number PM0075830. The modelled protein structure was subjected to In silco analysis using various bioinformatics tools. Two anti-influenza drugs currently being used to treat infected patients are oseltamivir (Tamiflu and zanamivir (Relenza, both of which target the neuraminidase enzyme of the virus. Reports of the emergence of drug resistance make the development of new anti-influenza molecules a priority. Hence the modelled structure of H1NI Neuraminidase could be very useful for in silico analysis of potential neuraminidase inhibitors.

  3. The knowledge of the importance on the influenza virus a (H1N1: experience report

    Directory of Open Access Journals (Sweden)

    Jaine Kareny da Silva

    2016-01-01

    Full Text Available Background and Objectives: Although infection rates by influenza A H1N1, present reduction since 2010 through immunization, it is still notorious some cases and outbreaks of the disease in the country. To minimize such cases it is important, among other measures, the qualification of the health worker. In this sense, the objective was to describe the level of awareness of nursing professionals in a hospital Bahia interior, on the transmission of the H1N1 virus, symptoms and what PPE is needed in assisting patients with suspected or diagnostic confirmation. Methods: This is an experience report experienced by nursing students at the State University of Bahia, who developed curricular component activities Caring Process: Rationale and practice in a public hospital in Bahia. The report data is from the collection conducted with the nurses, addressing aspects of symptoms, transmission and personal protective equipment. Each professional nursing spontaneously answered the questions and the end was discussed each item aiming answer questions by promoting thus an educational activity based on the knowledge of professionals. Results: Although most participants recognize the personal protective equipment and the symptoms of the viral disease, some are still unaware of the transmission routes. Most received no training on the subject. Conclusion: It is necessary to implement a Center for Continuing Education to answer questions about this and other topics, but are not limited to specific actions and seeking partnerships with higher education institutions. KEYWORDS: Education, Continuing. Education, Nursing. Disease Transmission, Infectious. Communicable Disease Control

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

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    Eric A Weaver

    Full Text Available 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.

  5. Experimental infection with a Thai reassortant swine influenza virus of pandemic H1N1 origin induced disease.

    Science.gov (United States)

    Charoenvisal, Nataya; Keawcharoen, Juthatip; Sreta, Donruethai; Tantawet, Siriporn; Jittimanee, Suphattra; Arunorat, Jirapat; Amonsin, Alongkorn; Thanawongnuwech, Roongroje

    2013-03-16

    Following the emergence of the pandemic H1N1 influenza A virus in 2009 in humans, this novel virus spread into the swine population. Pigs represent a potential host for this virus and can serve as a mixing vessel for genetic mutations of the influenza virus. Reassortant viruses eventually emerged from the 2009 pandemic and were reported in swine populations worldwide including Thailand. As a result of the discovery of this emergent disease, pathogenesis studies of this novel virus were conducted in order that future disease protection and control measures in swine and human populations could be enacted. The pandemic H1N1 2009 virus (pH1N1) and its reassortant virus (rH1N1) isolated from pigs in Thailand were inoculated into 2 separate cohorts of 9, 3-week-old pigs. Cohorts were consisted of one group experimentally infected with pH1N1 and one group with rH1N1. A negative control group consisting of 3 pigs was also included. Clinical signs, viral shedding and pathological lesions were investigated and compared. Later, 3 pigs from viral inoculated groups and 1 pig from the control group were necropsied at 2, 4, and 12 days post inoculation (DPI). The results indicated that pigs infected with both viruses demonstrated typical flu-like clinical signs and histopathological lesions of varying severity. Influenza infected-pigs of both groups had mild to moderate pulmonary signs on 1-4 DPI. Interestingly, pigs in both groups demonstrated viral RNA detection in the nasal swabs until the end of the experiment (12 DPI). The present study demonstrated that both the pH1N1 and rH1N1 influenza viruses, isolated from naturally infected pigs, induced acute respiratory disease in experimentally inoculated nursery pigs. Although animals in the rH1N1-infected cohort demonstrated more severe clinical signs, had higher numbers of pigs shedding the virus, were noted to have increased histopathological severity of lung lesions and increased viral antigen in lung tissue, the findings were

  6. Development and characterization of a panel of cross-reactive monoclonal antibodies generated using H1N1 influenza virus.

    Science.gov (United States)

    Guo, Chun-yan; Tang, Yi-gui; Qi, Zong-li; Liu, Yang; Zhao, Xiang-rong; Huo, Xue-ping; Li, Yan; Feng, Qing; Zhao, Peng-hua; Wang, Xin; Li, Yuan; Wang, Hai-fang; Hu, Jun; Zhang, Xin-jian

    2015-08-01

    To characterize the antigenic epitopes of the hemagglutinin (HA) protein of H1N1 influenza virus, a panel consisting of 84 clones of murine monoclonal antibodies (mAbs) were generated using the HA proteins from the 2009 pandemic H1N1 vaccine lysate and the seasonal influenza H1N1(A1) vaccines. Thirty-three (39%) of the 84 mAbs were found to be strain-specific, and 6 (7%) of the 84 mAbs were subtype-specific. Twenty (24%) of the 84 mAbs recognized the common HA epitopes shared by 2009 pandemic H1N1, seasonal A1 (H1N1), and A3 (H3N2) influenza viruses. Twenty-five of the 84 clones recognized the common HA epitopes shared by the 2009 pandemic H1N1, seasonal A1 (H1N1) and A3 (H3N2) human influenza viruses, and H5N1 and H9N2 avian influenza viruses. We found that of the 16 (19%) clones of the 84 mAbs panel that were cross-reactive with human respiratory pathogens, 15 were made using the HA of the seasonal A1 (H1N1) virus and 1 was made using the HA of the 2009 pandemic H1N1 influenza virus. Immunohistochemical analysis of the tissue microarray (TMA) showed that 4 of the 84 mAb clones cross-reacted with human tissue (brain and pancreas). Our results indicated that the influenza virus HA antigenic epitopes not only induce type-, subtype-, and strain-specific monoclonal antibodies against influenza A virus but also cross-reactive monoclonal antibodies against human tissues. Further investigations of these cross-reactive (heterophilic) epitopes may significantly improve our understanding of viral antigenic variation, epidemics, pathophysiologic mechanisms, and adverse effects of influenza vaccines.

  7. Immunogenicity of Virus Like Particle Forming Baculoviral DNA Vaccine against Pandemic Influenza H1N1.

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    Yong-Dae Gwon

    Full Text Available An outbreak of influenza H1N1 in 2009, representing the first influenza pandemic of the 21st century, was transmitted to over a million individuals and claimed 18,449 lives. The current status in many countries is to prepare influenza vaccine using cell-based or egg-based killed vaccine. However, traditional influenza vaccine platforms have several limitations. To overcome these limitations, many researchers have tried various approaches to develop alternative production platforms. One of the alternative approach, we reported the efficacy of influenza HA vaccination using a baculoviral DNA vaccine (AcHERV-HA. However, the immune response elicited by the AcHERV-HA vaccine, which only targets the HA antigen, was lower than that of the commercial killed vaccine. To overcome the limitations of this previous vaccine, we constructed a human endogenous retrovirus (HERV envelope-coated, baculovirus-based, virus-like-particle (VLP-forming DNA vaccine (termed AcHERV-VLP against pandemic influenza A/California/04/2009 (pH1N1. BALB/c mice immunized with AcHERV-VLP (1×107 FFU AcHERV-VLP, i.m. and compared with mice immunized with the killed vaccine or mice immunized with AcHERV-HA. As a result, AcHERV-VLP immunization produced a greater humoral immune response and exhibited neutralizing activity with an intrasubgroup H1 strain (PR8, elicited neutralizing antibody production, a high level of interferon-γ secretion in splenocytes, and diminished virus shedding in the lung after challenge with a lethal dose of influenza virus. In conclusion, VLP-forming baculovirus DNA vaccine could be a potential vaccine candidate capable of efficiently delivering DNA to the vaccinee and VLP forming DNA eliciting stronger immunogenicity than egg-based killed vaccines.

  8. A case with myocarditis secondary to Influenza virus (H1N1

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    Fesih Aktar

    2015-09-01

    Full Text Available Although influenza is an acute and uncomplicated disease, that limits itself in the healthy children, it may lead to death by rarely forming the sickness. The most common complication of influenza is pneumonia and it is a rare complication which is developed together with myocarditis by influenza A and B viruses. A 32 months-old male patient was admitted for rapidly developed respiratory distress and tachycardia after fever, cough, vomiting, malaise and runny nose. His general status was medium, he had conscious and had hepatomegaly, tachycardia, dyspnea, tachypnea, intercostal-subcostal retractions and bilateral rhonchus. Cardiac enzyme levels and other laboratory parameters were found normal. Myocarditis and ejection fraction was determined as 42% in echocardiography. However, hospitalization hours between 24 and 48, the patient, whose significant respiratory compromise developed, was intubated and fastened to a mechanical ventilator. H1N1 is produce in nasopharyngeal swab culture at the sixth day of follow-up. Because we think H1N1 virus was responsible from current myocarditis, oseltamivir treatment was initiated. In the fourth day of the treatment the patient’s fever returned to normal, in the ninth day a dramatic recovery was observed. In tracking echocardiography, a significant improvement was observed in the ejection fraction and myocarditis picture compared with admission time. This case was presented in order to remind that in a patients, who present with influenza findings but have respiratory distress and tachycardia in addition to lower respiratory tract infection, myocarditis should also be considered in the differential diagnosis and to remind that promising results could be obtained with the early diagnosis and treatment.

  9. Assessing Google flu trends performance in the United States during the 2009 influenza virus A (H1N1 pandemic.

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    Samantha Cook

    Full Text Available BACKGROUND: Google Flu Trends (GFT uses anonymized, aggregated internet search activity to provide near-real time estimates of influenza activity. GFT estimates have shown a strong correlation with official influenza surveillance data. The 2009 influenza virus A (H1N1 pandemic [pH1N1] provided the first opportunity to evaluate GFT during a non-seasonal influenza outbreak. In September 2009, an updated United States GFT model was developed using data from the beginning of pH1N1. METHODOLOGY/PRINCIPAL FINDINGS: We evaluated the accuracy of each U.S. GFT model by comparing weekly estimates of ILI (influenza-like illness activity with the U.S. Outpatient Influenza-like Illness Surveillance Network (ILINet. For each GFT model we calculated the correlation and RMSE (root mean square error between model estimates and ILINet for four time periods: pre-H1N1, Summer H1N1, Winter H1N1, and H1N1 overall (Mar 2009-Dec 2009. We also compared the number of queries, query volume, and types of queries (e.g., influenza symptoms, influenza complications in each model. Both models' estimates were highly correlated with ILINet pre-H1N1 and over the entire surveillance period, although the original model underestimated the magnitude of ILI activity during pH1N1. The updated model was more correlated with ILINet than the original model during Summer H1N1 (r = 0.95 and 0.29, respectively. The updated model included more search query terms than the original model, with more queries directly related to influenza infection, whereas the original model contained more queries related to influenza complications. CONCLUSIONS: Internet search behavior changed during pH1N1, particularly in the categories "influenza complications" and "term for influenza." The complications associated with pH1N1, the fact that pH1N1 began in the summer rather than winter, and changes in health-seeking behavior each may have played a part. Both GFT models performed well prior to and during pH1

  10. Assessing Google Flu Trends Performance in the United States during the 2009 Influenza Virus A (H1N1) Pandemic

    Science.gov (United States)

    Cook, Samantha; Conrad, Corrie; Fowlkes, Ashley L.; Mohebbi, Matthew H.

    2011-01-01

    Background Google Flu Trends (GFT) uses anonymized, aggregated internet search activity to provide near-real time estimates of influenza activity. GFT estimates have shown a strong correlation with official influenza surveillance data. The 2009 influenza virus A (H1N1) pandemic [pH1N1] provided the first opportunity to evaluate GFT during a non-seasonal influenza outbreak. In September 2009, an updated United States GFT model was developed using data from the beginning of pH1N1. Methodology/Principal Findings We evaluated the accuracy of each U.S. GFT model by comparing weekly estimates of ILI (influenza-like illness) activity with the U.S. Outpatient Influenza-like Illness Surveillance Network (ILINet). For each GFT model we calculated the correlation and RMSE (root mean square error) between model estimates and ILINet for four time periods: pre-H1N1, Summer H1N1, Winter H1N1, and H1N1 overall (Mar 2009–Dec 2009). We also compared the number of queries, query volume, and types of queries (e.g., influenza symptoms, influenza complications) in each model. Both models' estimates were highly correlated with ILINet pre-H1N1 and over the entire surveillance period, although the original model underestimated the magnitude of ILI activity during pH1N1. The updated model was more correlated with ILINet than the original model during Summer H1N1 (r = 0.95 and 0.29, respectively). The updated model included more search query terms than the original model, with more queries directly related to influenza infection, whereas the original model contained more queries related to influenza complications. Conclusions Internet search behavior changed during pH1N1, particularly in the categories “influenza complications” and “term for influenza.” The complications associated with pH1N1, the fact that pH1N1 began in the summer rather than winter, and changes in health-seeking behavior each may have played a part. Both GFT models performed well prior to and during pH1N1

  11. Clinical and radiological features of pandemic H1N1 2009 influenza virus infection manifesting as acute febrile respiratory illness at their initial presentations: comparison with contemporaneous non-H1N1 patients

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    Yun, Tae Jin (Dept. of Radiology, Armed Force Byukjae Hospital, Gyeonggi-do (Korea, Republic of); Dept. of Radiology, Seoul National Univ. Hospital, Seoul (Korea, Republic of)); Park, Chang Min; Choi, Seung Hong; Lee, Hyun Ju; Goo, Jin Mo (Dept. of Radiology, Seoul National Univ. Hospital, Seoul (Korea, Republic of)), email: cmpark@radiol.snu.ac.kr; Kwon, Gu Jin (Dept. of Family Medicine, Armed Force Byukjae Hospital, Gyeonggi-do (Korea, Republic of); Dept. of Family Medicine, Gangneung Asan Hospital, Gangneung (Korea, Republic of)); Woo, Sung Koo (Dept. of Radiology, Armed Force Byukjae Hospital, Gyeonggi-do (Korea, Republic of)); Park, Seung Hoon (Dept. of Internal Medicine, Armed Force Byukjae Hospital, Gyeonggi-do (Korea, Republic of))

    2011-05-15

    Background Since the first outbreak caused by the pandemic H1N1 2009 influenza in Mexico, the virus has spread widely across the world with meaningful morbidity and mortality. However, there are few data on the comparative investigations to assess the clinical and radiological features between the H1N1 patient and non-H1N1 patients. Purpose To assess the clinical and radiological features of patients infected by the pandemic H1N1 2009 flu virus at their initial presentation and to compare them with contemporaneous non-H1N1 patients with acute febrile respiratory illness. Material and Methods This retrospective study was approved by the ethics committee of the Armed Forces Medical Command, South Korea. From August to September 2009, 337 consecutive patients presented with an acute febrile respiratory illness in a tertiary military hospital. Reverse-transcriptase polymerase-chain-reaction tests were performed in 62 of these patients under the impression of H1N1 infection. Clinical and radiological features at their initial presentation were described for the H1N1 group (n = 35) and non-H1N1 group (n = 27) and compared between the two groups. Results Increased C-reactive protein level (97%) without leukocytosis (9%) or increased erythrocyte sedimentation rate (0%) was common in the H1N1 group at their initial presentation. On chest radiographs, 12 of 35 (34%) H1N1 patients had abnormal findings; nodules in 10 patients (83%) and consolidations in two (17%). Of the 28 H1N1 patients who underwent thin-section CT 16 patients (57%) showed abnormal findings; ground-glass opacities (GGOs) in 15 (94%), and nodules in 13 (81%). However, there were no significant differences between the H1N1 group and non-H1N1 group in terms of symptoms, laboratory results, or radiological findings (P > 0.05). Conclusion Patients with H1N1 infection show consistent clinical and radiological features at their initial presentation, however, clinical and radiological features of the H1N1 group are

  12. Immunosensor based on the ZnO nanorod networks for the detection of H1N1 swine influenza virus.

    Science.gov (United States)

    Jang, Yunseok; Park, Jungil; Pak, Youngmi Kim; Pak, James Jungho

    2012-07-01

    This paper presents an immunosensor fabricated on patterned zinc oxide nanorod networks (ZNNs) for detecting the H1N1 swine influenza virus (H1N1 SIV). Nanostructured ZnO with a high isoelectric point (IEP, approximately 9.5) possesses good absorbability for proteins with low IEPs. Hydrothermally grown ZNNs were fabricated on a patterned Au electrode (0.02 cm2) through a lift-off process. To detect the H1N1 SIV, the sandwich enzyme-linked immunosorbent assay (ELISA) method was employed in the immunosensor. The immunosensor was evaluated in an acetate buffer solution containing 3,3',5,5'-tetramethylbenzidine (TMB) via cyclic voltammetry at various H1N1 SIV concentrations (1 pg/mL-5 ng/mL). The measurement results of the fabricated immunosensor showed that the reduction currents of TMB at 0.25 V logarithmically increased from 259.37 to 577.98 nA as the H1N1 SIV concentration changed from 1 pg/mL to 5 ng/mL. An H1N1 SIV immunosensor, based on the patterned ZNNs, was successfully realized for detecting 1 pg/mL-5 ng/mL H1N1 SIV concentrations, with a detection limit of 1 pg/mL for H1N1 SIV.

  13. Guidance for Testing and Labeling Claims against Pandemic 2009 H1N1 Influenza A Virus (Formerly called Swine Flu )

    Science.gov (United States)

    This document provides guidance labeling and testing for antimicrobial pesticides in several forms that are used to treat hard non-porous surfaces in healthcare facilities and other settings against Pandemic 2009 H1N1 influenza A Virus.

  14. Epidemiological and virological characterization of 2009 pandemic influenza A virus subtype H1N1 in Madagascar.

    Science.gov (United States)

    Orelle, Arnaud; Razanajatovo, Norosoa Harline; Rajatonirina, Soatiana; Hoffmann, Jonathan; Randrianasolo, Laurence; Razafitrimo, Girard Marcellin; Naidoo, Dhamari; Richard, Vincent; Heraud, Jean-Michel

    2012-12-15

    Madagascar was one of the first African countries to be affected by the 2009 pandemic of influenza A virus subtype H1N1 [A(H1N1)pdm2009] infection. The outbreak started in the capital city, Antananarivo, and then spread throughout the country from October 2009 through February 2010. Specimens from patients presenting with influenza-like illness were collected and shipped to the National Influenza Center in Madagascar for analyses, together with forms containing patient demographic and clinical information. Of the 2303 specimens tested, 1016 (44.1%) and 131 (5.7%) yielded A(H1N1)pdm09 and seasonal influenza virus, respectively. Most specimens (42.0%) received were collected from patients 50 years old to be infected with A(H1N1)pdm09 (odds ratio, 2.1; 95% confidence interval, 1.7-2.6; P Madagascar, no antigenic differences between A(H1N1)pdm09 viruses recovered in Madagascar and those that circulated worldwide were observed. The high proportion of respiratory specimens positive for A(H1N1)pdm09 is consistent with a widespread transmission of the pandemic in Madagascar. The age distribution of cases of A(H1N1)pdm09 infection suggests that children and young adults could be targeted for interventions that aim to reduce transmission during an influenza pandemic.

  15. Horizontal transmission of novel H1N1/09 influenza virus in a newborn:Myth or fact?

    Institute of Scientific and Technical Information of China (English)

    Uttam Kumar Sarkar; Utpala Mitra; Mamta Chawla Sarkar; Shanta Dutta; Himanish Roy; Mrinal Kanti Chatterjee; Phalguni Dutta

    2012-01-01

    Horizontal transmission of H1N1/09 virus infection is very common however; transmission through this route has not been reported in newborns. To our knowledge, this is the first case report of newborn who acquired infection of novel H1N1/09 virus horizontally through asymptomatic family members or hospital staff during epidemic period in Kolkata, India. Baby recovered without antiviral therapy but received antibiotic for bacterial co-infection.

  16. Pandemic H1N1 2009 virus in Danish pigs: Diagnosis and lack of surveillance

    DEFF Research Database (Denmark)

    Larsen, Lars Erik; Nielsen, L. P.; Breum, Solvej Østergaard

    the constraints put on the herd in case of a positive H1N1v result. In combination with the fact that Denmark does not have any formal surveillance program for swine influenza in place, we have currently no overview of the number of H1N1v positive swine in Denmark. However, the diagnosis of a positive herd...

  17. Fitness of Pandemic H1N1 and Seasonal influenza A viruses during Co-infection: Evidence of competitive advantage of pandemic H1N1 influenza versus seasonal influenza.

    Science.gov (United States)

    Perez, Daniel Roberto; Sorrell, Erin; Angel, Matthew; Ye, Jianqiang; Hickman, Danielle; Pena, Lindomar; Ramirez-Nieto, Gloria; Kimble, Brian; Araya, Yonas

    2009-08-24

    On June 11, 2009 the World Health Organization (WHO) declared a new H1N1 influenza pandemic. This pandemic strain is as transmissible as seasonal H1N1 and H3N2 influenza A viruses. Major concerns facing this pandemic are whether the new virus will replace, co-circulate and/or reassort with seasonal H1N1 and/or H3N2 human strains. Using the ferret model, we investigated which of these three possibilities were most likely favored. Our studies showed that the current pandemic virus is more transmissible than, and has a biological advantage over, prototypical seasonal H1 or H3 strains.

  18. Properly folded bacterially expressed H1N1 hemagglutinin globular head and ectodomain vaccines protect ferrets against H1N1 pandemic influenza virus.

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    Surender Khurana

    Full Text Available BACKGROUND: In the face of impending influenza pandemic, a rapid vaccine production and mass vaccination is the most effective approach to prevent the large scale mortality and morbidity that was associated with the 1918 "Spanish Flu". The traditional process of influenza vaccine production in eggs is time consuming and may not meet the demands of rapid global vaccination required to curtail influenza pandemic. METHODOLOGY/PRINCIPAL FINDINGS: Recombinant technology can be used to express the hemagglutinin (HA of the emerging new influenza strain in a variety of systems including mammalian, insect, and bacterial cells. In this study, two forms of HA proteins derived from the currently circulating novel H1N1 A/California/07/2009 virus, HA1 (1-330 and HA (1-480, were expressed and purified from E. coli under controlled redox refolding conditions that favoured proper protein folding. However, only the recombinant HA1 (1-330 protein formed oligomers, including functional trimers that bound receptor and caused agglutination of human red blood cells. These proteins were used to vaccinate ferrets prior to challenge with the A/California/07/2009 virus. Both proteins induced neutralizing antibodies, and reduced viral loads in nasal washes. However, the HA1 (1-330 protein that had higher content of multimeric forms provided better protection from fever and weight loss at a lower vaccine dose compared with HA (1-480. Protein yield for the HA1 (1-330 ranged around 40 mg/Liter, while the HA (1-480 yield was 0.4-0.8 mg/Liter. CONCLUSIONS/SIGNIFICANCE: This is the first study that describes production in bacterial system of properly folded functional globular HA1 domain trimers, lacking the HA2 transmembrane protein, that elicit potent neutralizing antibody responses following vaccination and protect ferrets from in vivo challenge. The combination of bacterial expression system with established quality control methods could provide a mechanism for rapid large

  19. Influenza virus H1N1 activates platelets through FcγRIIA signaling and thrombin generation.

    Science.gov (United States)

    Boilard, Eric; Paré, Guillaume; Rousseau, Matthieu; Cloutier, Nathalie; Dubuc, Isabelle; Lévesque, Tania; Borgeat, Pierre; Flamand, Louis

    2014-05-01

    Platelets play crucial functions in hemostasis and the prevention of bleeding. During H1N1 influenza A virus infection, platelets display activation markers. The platelet activation triggers during H1N1 infection remain elusive. We observed that H1N1 induces surface receptor activation, lipid mediator synthesis, and release of microparticles from platelets. These activation processes require the presence of serum/plasma, pointing to the contribution of soluble factor(s). Considering that immune complexes in the H1N1 pandemic were reported to play a pathogenic role, we assessed their contribution in H1N1-induced platelet activation. In influenza-immunized subjects, we observed that the virus scaffolds with immunoglobulin G (IgG) to form immune complexes that promote platelet activation. Mechanistically, this activation occurs through stimulation of low-affinity type 2 receptor for Fc portion of IgG (FcγRIIA), a receptor for immune complexes, independently of thrombin. Using a combination of in vitro and in vivo approaches, we found that the antibodies from H3N2-immunized mice activate transgenic mouse platelets that express FcγRIIA when put in the presence of H1N1, suggesting that cross-reacting influenza antibodies suffice. Alternatively, H1N1 can activate platelets via thrombin formation, independently of complement and FcγRIIA. These observations identify both the adaptive immune response and the innate response against pathogens as 2 intertwined processes that activate platelets during influenza infections.

  20. Changes in the viral distribution pattern after the appearance of the novel influenza A H1N1 (pH1N1 virus in influenza-like illness patients in Peru.

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    Victor Alberto Laguna-Torres

    Full Text Available BACKGROUND: We describe the temporal variation in viral agents detected in influenza like illness (ILI patients before and after the appearance of the ongoing pandemic influenza A (H1N1 (pH1N1 in Peru between 4-January and 13-July 2009. METHODS: At the health centers, one oropharyngeal swab was obtained for viral isolation. From epidemiological week (EW 1 to 18, at the US Naval Medical Research Center Detachment (NMRCD in Lima, the specimens were inoculated into four cell lines for virus isolation. In addition, from EW 19 to 28, the specimens were also analyzed by real time-polymerase-chain-reaction (rRT-PCR. RESULTS: We enrolled 2,872 patients: 1,422 cases before the appearance of the pH1N1 virus, and 1,450 during the pandemic. Non-pH1N1 influenza A virus was the predominant viral strain circulating in Peru through (EW 18, representing 57.8% of the confirmed cases; however, this predominance shifted to pH1N1 (51.5% from EW 19-28. During this study period, most of pH1N1 cases were diagnosed in the capital city (Lima followed by other cities including Cusco and Trujillo. In contrast, novel influenza cases were essentially absent in the tropical rain forest (jungle cities during our study period. The city of Iquitos (Jungle had the highest number of influenza B cases and only one pH1N1 case. CONCLUSIONS: The viral distribution in Peru changed upon the introduction of the pH1N1 virus compared to previous months. Although influenza A viruses continue to be the predominant viral pathogen, the pH1N1 virus predominated over the other influenza A viruses.

  1. Differentiation of human influenza A viruses including the pandemic subtype H1N1/2009 by conventional multiplex PCR.

    Science.gov (United States)

    Furuse, Yuki; Odagiri, Takashi; Okada, Takashi; Khandaker, Irona; Shimabukuro, Kozue; Sawayama, Rumi; Suzuki, Akira; Oshitani, Hitoshi

    2010-09-01

    April 2009 witnessed the emergence of a novel H1N1 influenza A virus infecting the human population. Currently, pandemic and seasonal influenza viruses are co-circulating in human populations. Understanding the course of the emerging pandemic virus is important. It is still unknown how the novel virus co-circulates with or outcompetes seasonal viruses. Sustainable and detailed influenza surveillance is required throughout the world including developing countries. In the present study, a multiplex PCR using four primers was developed, which was designed to differentiate the pandemic H1N1 virus from the seasonal H1N1 and H3N2 viruses, to obtain amplicons of different sizes. Multiplex PCR analysis could clearly differentiate the three subtypes of human influenza A virus. This assay was performed using 206 clinical samples collected in 2009 in Japan. Between February and April, four samples were subtyped as seasonal H1N1 and four as seasonal H3N2. All samples collected after July were subtyped as pandemic H1N1. Currently, pandemic viruses seem to have replaced seasonal viruses almost completely in Japan. This is a highly sensitive method and its cost is low. Influenza surveillance using this assay would provide significant information on the epidemiology of both pandemic and seasonal influenza.

  2. Los virus Influenza y la nueva pandemia A/H1N1

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    Miguel Talledo

    2011-07-01

    Full Text Available Los virus Influenza pertenecen a la familia Orthomyxoviridae, virus con genoma RNA de sentido negativo segmentado. Los virus influenza tipo A infectan a humanos y otros organismos, y son los agentes causantes de influenza en humanos. Resaltan entre sus principales proteínas la Hemaglutinina y la Neuraminidasa, que son utilizadas en la clasificación de los miembros de este grupo. Estos virus mutan continuamente, exhibiendo patrones muy estudiados, como el cambio y la deriva antigénica, siendo uno de los principales eventos de recombinación el reordenamiento. Todos los subtipos se encuentran en aves acuáticas silvestres, aunque se han encontrado otros hospederos, como equinos, visones, ballenas, focas, cerdos, gallinas y pavos, entre otros. Tanto las aves salvajes, las aves domésticas y el cerdo juegan un rol fundamental en la adaptación progresiva del virus al hospedero humano. Aunque los subtipos H2N2 y H3N2 han sido muy comunes, el subtipo H1N1 ha reemergido con mutaciones que le han permitido alcanzar el estado de pandemia en 2009. Este nuevo virus surge de un virus generado por triple reordenamiento con el virus humano, porcino norteamericano y aviar, conteniendo a su vez segmentos génicos de virus influenza porcina euroasiática. Esto ha hecho que el virus presente una enfermedad humana moderada y solamente severa y hasta letal en casos de individuos con condiciones médicas previas. A nivel mundial ha causado más de 134,510 casos y en el Perú alcanza cerca de 3,700 casos. El estado actual indica que la pandemia está por llegar a su pico máximo en el Perú, debido a la alta morbilidad del virus coincidente con la estación más fría del año. Es importante contener al máximo la dispersión del virus, ya que cuanto mayor sea el número de personas que infecte, el mismo estará sometido a un mayor número de eventos de recombinación genética por reordenamiento con virus influenza humanos previos y esto puede condicionar a la

  3. Persistence of the 2009 pandemic influenza A (H1N1 virus in water and on non-porous surface.

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    Amélie Dublineau

    Full Text Available Knowledge of influenza A virus survival in different environmental conditions is a key element for the implementation of hygiene and personal protection measures by health authorities. As it is dependent on virus isolates even within the same subtype, we studied the survival of the 2009 H1N1 pandemic (H1N1pdm virus in water and on non-porous surface. The H1N1pdm virus was subjected to various environmental parameters over time and tested for infectivity. In water, at low and medium salinity levels and 4°C, virus survived at least 200 days. Increasing temperature and salinity had a strong negative effect on the survival of the virus which remained infectious no more than 1 day at 35°C and 270 parts per thousand (ppt of salt. Based on modeled data, the H1N1pdm virus retained its infectivity on smooth non-porous surface for at least 7 days at 35°C and up to 66 days at 4°C. The H1N1pdm virus has thus the ability to persist in water and on glass surface for extended periods of time, even at 35°C. Additional experiments suggest that external viral structures in direct contact with the environment are mostly involved in loss of virus infectivity.

  4. Influenza A(H1N1) Oseltamivir Resistant Viruses in the Netherlands During the Winter 2007/2008

    Science.gov (United States)

    Dijkstra, Frederika; Jonges, Marcel; van Beek, Ruud; Donker, Gé A; Schellevis, François G; Koopmans, Marion; van der Sande, Marianne A.B; Osterhaus, Albert D.M.E; Boucher, Charles A.B; Rimmelzwaan, Guus F; Meijer, Adam

    2011-01-01

    Background: Antiviral susceptibility surveillance in the Netherlands was intensified after the first reports about the emergence of influenza A(H1N1) oseltamivir resistant viruses in Norway in January, 2008. Methods: Within the existing influenza surveillance an additional questionnaire study was performed to retrospectively assess possible risk factors and establish clinical outcome of all patients with influenza virus A(H1N1) positive specimens. To discriminate resistant and sensitive viruses, fifty percent inhibitory concentrations for the neuramidase inhibitors oseltamivir and zanamivir were determined in a neuraminidase inhibition assay. Mutations previously associated with resistance to neuramidase inhibitors and M2 blockers (amantadine and rimantadine) were searched for by nucleotide sequencing of neuraminidase and M2 genes respectively. Results: Among 171 patients infected with A(H1N1) viruses an overall prevalence of oseltamivir resistance of 27% (95% CI: 20-34%) was found. None of influenza A(H1N1) oseltamivir resistant viruses tested was resistant against amantadine or zanamivir. Patient characteristics, underlying conditions, influenza vaccination, symptoms, complications, and exposure to oseltamivir and other antivirals did not differ significantly between patients infected with resistant and sensitive A(H1N1) viruses. Conclusion: In 2007/2008 a large proportion of influenza A(H1N1) viruses resistant to oseltamivir was detected. There were no clinical differences between patients infected with resistant and sensitive A(H1N1) viruses. Continuous monitoring of the antiviral drug sensitivity profile of influenza viruses is justified, preferably using the existing sentinel surveillance, however, complemented with data from the more severe end of the clinical spectrum. In order to act timely on emergencies of public health importance we suggest setting up a surveillance system that can guarantee rapid access to the latter. PMID:22253652

  5. 关于甲型H1N1流感病毒预防及控制措施%Prevention and Control Measures on H1N1 Influenza Virus

    Institute of Scientific and Technical Information of China (English)

    2013-01-01

    H1N1 influenza virus is a kind of world infectious diseases, and we should strengthen the flu virus prevention and control, so it’s very important. In this paper, at first the influenza H1N1 influenza virus is analyzed and introduced, and then puts forward the virus prevention and control measures.%  甲型H1N1流感病毒是一种世界性的传染病,加强该流感病毒的预防和控制是十分重要的。本文首先对甲型H1N1流感病毒进行了分析介绍,然后提出了该病毒的预防和控制措施。

  6. Thoracic computerized tomographic (CT findings in 2009 influenza A (H1N1 virus infection in Isfahan, Iran

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    Mojtaba Rostami

    2011-01-01

    Full Text Available Background: Pandemic 2009 H1N1 influenza A virus arrived at Isfahan in August 2009. The virus is still circulating in the world. The abnormal thoracic computerized tomographic (CT scan findings vary widely among the studies of 2009 H1N1 influenza. We evaluated the thoracic CT findings in patients with 2009 H1N1 virus infection to describe findings compared to previously reported findings, and to suggest patterns that may be suggestive for 2009 influenza A (H1N1 in an appropriate clinical setting. Methods: Retrospectively, the archive of all patients with a diagnosis of 2009 H1N1 influenza A were reviewed, in Al-Zahra Hospital in Isfahan, central Iran, between September 23 rd 2009 to February 20 th 2010. Out of 216 patients with confirmed 2009 influenza A (H1N1 virus, 26 cases with abnormal CT were enrolled in the study. Radiologic findings were characterized by the type and pattern of opacities and zonal distribution. Results: Patchy infiltration (34.6%, lobar consolidation (30.8%, and interstitial infiltration (26.9% with airbronchogram (38.5% were the predominant findings in our patients. Bilateral distribution was seen in 80.8% of the patients. Only one patient (3.8% showed ground-glass opacity, predominant radiographic finding in the previous reports and severe acute respiratory syndrome (SARS. Conclusions: The most common thoracic CT findings in pandemic H1N1 were patchy infiltration, lobar consolidation, and interstitial infiltration with airbronchogram and bilateral distribution. While these findings can be associated with other infections; they may be suggestive to 2009 influenza A (H1N1 in the appropriate clinical setting. Various radiographic patterns can be seen in thoracic CT scans of the influenza patients. Imaging findings are nonspecific.

  7. Potency of a vaccine prepared from A/swine/Hokkaido/2/1981 (H1N1 against A/Narita/1/2009 (H1N1 pandemic influenza virus strain

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    Okamatsu Masatoshi

    2013-02-01

    Full Text Available Abstract Background The pandemic 2009 (H1N1 influenza virus has spread throughout the world and is now causing seasonal influenza. To prepare for the emergence of pandemic influenza, we have established a library of virus strains isolated from birds, pigs, and humans in global surveillance studies. Methods Inactivated whole virus particle (WV and ether-split (ES vaccines were prepared from an influenza virus strain, A/swine/Hokkaido/2/1981 (H1N1, from the library and from A/Narita/1/2009 (H1N1 pandemic strain. Each of the vaccines was injected subcutaneously into mice and their potencies were evaluated by challenge with A/Narita/1/2009 (H1N1 virus strain in mice. Results A/swine/Hokkaido/2/81 (H1N1, which was isolated from the lung of a diseased piglet, was selected on the basis of their antigenicity and growth capacity in embryonated chicken eggs. Two injections of the WV vaccine induced an immune response in mice, decreasing the impact of disease caused by the challenge with A/Narita/1/2009 (H1N1, as did the vaccine prepared from the homologous strain. Conclusion The WV vaccine prepared from an influenza virus in the library is useful as an emergency vaccine in the early phase of pandemic influenza.

  8. Melissa offiinalis effiacy against human inflenza virus (New H1N1 in comparison with oseltamivir

    Directory of Open Access Journals (Sweden)

    Parvane Jalali

    2016-09-01

    Full Text Available Objective: To evaluate the antiviral activity of Melissa officinalis (MO extract against the influenza virus H1N1 in vitro. Methods: The cytotoxicity of MO extract was identified on Madin-Darby canine kidney (MDCK cell culture by MTT assay. The virus was inoculated to the cells (multiplicity of infection = 0.1 in two protocols. In protocol 1, the MO extracts at concentrations of 0.005, 0.050, 0.010, 0.100 and 0.500 mg/mL were incubated with the virus for one hour preinoculation. In protocol 2, the mentioned concentrations of MO extracts were added to the cells one-hour post infection. Furthermore, the antiviral effect of oseltamivir with different concentrations was tested as the positive controls. The 50% tissue culture infective dose, neutralizing index and hemagglutination titer were determined. Results: The medicine oseltamivir and MO extracts were not toxic for MDCK at concentrations less than 1 mg/mL. All utilized concentrations of MO extracts were vigorously efficient to decrease the viral yield in both experiments. The 50% tissue culture infective dose of the groups containing up to 0.100 mg/mL of MO extracts in the first experiment in compare with 0.050 mg/mL in the second experiment reduced to 0. Although hemagglutination tests showed little titers, the viral quantity significantly decreased in both experiments. By the way, the medicine oseltamivir could completely suppress viral replication in MDCK. Conclusions: The present study suggests that MO extracts have a potent anti-influenza effect in cell culture.

  9. Characterization In Vitro and In Vivo of a Pandemic H1N1 Influenza Virus from a Fatal Case

    Science.gov (United States)

    Cuevas, Maria Teresa; Pozo, Francisco; Guerra, Susana; García-Barreno, Blanca; Martinez-Orellana, Pamela; Pérez-Breña, Pilar; Montoya, Maria; Melero, Jose Antonio; Pizarro, Manuel; Ortin, Juan; Casas, Inmaculada; Nieto, Amelia

    2013-01-01

    Pandemic 2009 H1N1 (pH1N1) influenza viruses caused mild symptoms in most infected patients. However, a greater rate of severe disease was observed in healthy young adults and children without co-morbid conditions. Here we tested whether influenza strains displaying differential virulence could be present among circulating pH1N1 viruses. The biological properties and the genotype of viruses isolated from a patient showing mild disease (M) or from a fatal case (F), both without known co-morbid conditions were compared in vitro and in vivo. The F virus presented faster growth kinetics and stronger induction of cytokines than M virus in human alveolar lung epithelial cells. In the murine model in vivo, the F virus showed a stronger morbidity and mortality than M virus. Remarkably, a higher proportion of mice presenting infectious virus in the hearts, was found in F virus-infected animals. Altogether, the data indicate that strains of pH1N1 virus with enhanced pathogenicity circulated during the 2009 pandemic. In addition, examination of chemokine receptor 5 (CCR5) genotype, recently reported as involved in severe influenza virus disease, revealed that the F virus-infected patient was homozygous for the deleted form of CCR5 receptor (CCR5Δ32). PMID:23326447

  10. Corticosteroid treatment ameliorates acute lung injury induced by 2009 swine origin influenza A (H1N1 virus in mice.

    Directory of Open Access Journals (Sweden)

    Chenggang Li

    Full Text Available BACKGROUND: The 2009 influenza pandemic affected people in almost all countries in the world, especially in younger age groups. During this time, the debate over whether to use corticosteroid treatment in severe influenza H1N1 infections patients resurfaced and was disputed by clinicians. There is an urgent need for a susceptible animal model of 2009 H1N1 infection that can be used to evaluate the pathogenesis and the therapeutic effect of corticosteroid treatment during infection. METHODOLOGY/PRINCIPAL FINDINGS: We intranasally inoculated two groups of C57BL/6 and BALB/c mice (using 4- or 6-to 8-week-old mice to compare the pathogenesis of several different H1N1 strains in mice of different ages. Based on the results, a very susceptible 4-week-old C57BL/6 mouse model of Beijing 501 strain of 2009 H1N1 virus infection was established, showing significantly elevated lung edema and cytokine levels compared to controls. Using our established animal model, the cytokine production profile and lung histology were assessed at different times post-infection, revealing increased lung lesions in a time-dependent manner. In additional,the mice were also treated with dexamethasone, which significantly improved survival rate and lung lesions in infected mice compared to those in control mice. Our data showed that corticosteroid treatment ameliorated acute lung injury induced by the 2009 A/H1N1 virus in mice and suggested that corticosteroids are valid drugs for treating 2009 A/H1N1 infection. CONCLUSIONS/SIGNIFICANCE: Using the established, very susceptible 2009 Pandemic Influenza A (H1N1 mouse model, our studies indicate that corticosteroids are a potential therapeutic remedy that may address the increasing concerns over future 2009 A/H1N1 pandemics.

  11. Antibodies against avian-like A (H1N1) swine influenza virus among swine farm residents in eastern China.

    Science.gov (United States)

    Yin, Xiuchen; Yin, Xin; Rao, Baizhong; Xie, Chunfang; Zhang, Pengchao; Qi, Xian; Wei, Ping; Liu, Huili

    2014-04-01

    In 2007, the avian-like H1N1 virus (A/swine/Zhejiang/1/07) was first isolated in pigs in China. Recently, it was reported that a 3-year-old boy was infected with avian-like A (H1N1) swine influenza virus (SIV) in Jiangsu Province, China. To investigate the prevalence of avian-like A (H1N1) SIV infection among swine farm residents in eastern China, an active influenza surveillance program was conducted on swine farms in this region from May 21, 2010 through April 22, 2012. A total of 1,162 participants were enrolled, including 1,136 persons from 48 pig farms, as well as 26 pig farm veterinarians. A total of 10.7% and 7.8% swine farm residents were positive for antibodies against avian-like A (H1N1) SIV by HI and NT assay, respectively, using 40 as the cut-off antibody titer. Meanwhile, all the serum samples collected from a control of healthy city residents were negative against avian-like A (H1N1) SIV. As the difference in numbers of antibody positive samples between the swine farm residents and health city residents controls was statistically significant (P = 0.002), these data suggest that occupational exposure to pigs may increase swine farm residents' and veterinarians' risk of avian-like A (H1N1) SIV infection in eastern China. This study provides the first data on avian-like A (H1N1) SIV infections in humans in China; the potential for avian-like A (H1N1) SIV entering the human population should also be taken into consideration.

  12. [Colorimetric detection of human influenza A H1N1 virus by reverse transcription loop mediated isothermal amplification].

    Science.gov (United States)

    Nie, Kai; Wang, Da-Yan; Qin, Meng; Gao, Rong-Bao; Wang, Miao; Zou, Shu-Mei; Han, Feng; Zhao, Xiang; Li, Xi-Yan; Shu, Yue-Long; Ma, Xue-Jun

    2010-03-01

    A simple, rapid and sensitive colorimetric Reverse Transcription Loop Mediated Isothermal Amplification (RT-LAMP) method was established to detect human influenza A H1N1 virus. The method employed a set of six specially designed primers that recognized eight distinct sequences of the HA gene for amplification of nucleic acid under isothermal conditions at 65 degrees C for one and half hour. The amplification process of RT-LAMP was monitored by the addition of HNB (Hydroxy naphthol blue) dye prior to amplification. A positive reaction was indicated by a color change from violet to sky blue and confirmed by agarose electrophoresis. The specificity of the RT-LAMP assay was validated by cross-reaction with different swine and human influenza virus including human seasonal influenza A /H1N1 A /H3N2, influenza B and swine A /H1N1. The sensitivity of this assay was evaluated by serial dilutions of RNA molecules from in vitro transcription of human influenza A H1N1 HA gene. The assay was further evaluated with 30 clinical specimens with suspected pandemic influenza A H1N1 virus infection in parallel with RT-PCR detection and 26 clinical specimens with seasonal influenza virus infection. Our results showed that the RT-LAMP was able to achieve a sensitivity of 60 RNA copies with high specificity, and detection rate was comparable to that of the RT-PCR with the clinical samples of pandemic influenza A H1N1 infection. The RT-LAMP reaction with HNB could also be measured at 650nm in a microplate reader for quantitative analysis. Thus, we concluded that this colorimetric RT-LAMP assay had potential for the rapid screening of the human influenza A H1N1 virus infection in National influenza monitoring network laboratories and sentinel hospitals of provincial and municipal region in China.

  13. Agglutination of human O erythrocytes by influenza A(H1N1) viruses freshly isolated from patients.

    Science.gov (United States)

    Murakami, T; Haruki, K; Seto, Y; Kimura, T; Minoshiro, S; Shibe, K

    1991-04-01

    The hemagglutinin titers of 10 influenza A (H1N1) viruses were examined using the erythrocytes of several species. Human O erythrocytes showed the highest agglutination titer to the viruses, whereas chicken erythrocytes showed a low titer. These findings were noted for at least 10 passages by serial dilutions of the viruses in Madin-Darby canine kidney (MDCK) cells. All influenza A(H1N1) viruses, plaque-cloned directly from throat-washing specimens of patients, also agglutinated human O but not chicken erythrocytes. The results of a hemadsorption test indicated that chicken erythrocytes possess less affinity to MDCK cells infected with the A/Osaka City/2/88(H1N1) stain than to those infected with the A/Yamagata/120/86(H1N1) strain which is used as an inactivated influenza vaccine in Japan. However, there were no significant differences between the A/Osaka City/2/88 and the A/Yamagata/120/86 strains in the hemagglutination inhibition test. Since human O erythrocytes have high agglutination activity to influenza A(H1N1) and also to A(H3N2) and B viruses in MDCK cells, these erythrocytes may be useful for the serological diagnosis of influenza.

  14. Infectious Progeny of 2009 A (H1N1) Influenza Virus Replicated in and Released from Human Neutrophils.

    Science.gov (United States)

    Zhang, Zhang; Huang, Tao; Yu, Feiyuan; Liu, Xingmu; Zhao, Conghui; Chen, Xueling; Kelvin, David J; Gu, Jiang

    2015-12-07

    Various reports have indicated that a number of viruses could infect neutrophils, but the multiplication of viruses in neutrophils was abortive. Based on our previous finding that avian influenza viral RNA and proteins were present in the nucleus of infected human neutrophils in vivo, we investigated the possibility of 2009 A (H1N1) influenza viral synthesis in infected neutrophils and possible release of infectious progeny from host cells. In this study we found that human neutrophils in vitro without detectable level of sialic acid expression could be infected by this virus strain. We also show that the infected neutrophils can not only synthesize 2009 A (H1N1) viral mRNA and proteins, but also produce infectious progeny. These findings suggest that infectious progeny of 2009 A (H1N1) influenza virus could be replicated in and released from human neutrophils with possible clinical implications.

  15. Coinfection with influenza A(H1N1)pdm09 and dengue virus in fatal cases.

    Science.gov (United States)

    Perdigão, Anne Carolinne Bezerra; Ramalho, Izabel Letícia Cavalcante; Guedes, Maria Izabel Florindo; Braga, Deborah Nunes Melo; Cavalcanti, Luciano Pamplona Góes; Melo, Maria Elisabeth Lisboa de; Araújo, Rafael Montenegro de Carvalho; Lima, Elza Gadelha; Silva, Luciene Alexandre Bié da; Araújo, Lia de Carvalho; Araújo, Fernanda Montenegro de Carvalho

    2016-09-01

    We report on four patients with fatal influenza A(H1N1)pdm09 and dengue virus coinfections. Clinical, necropsy and histopathologic findings presented in all cases were characteristic of influenza-dengue coinfections, and all were laboratory-confirmed for both infections. The possibility of influenza and dengue coinfection should be considered in locations where these two viruses' epidemic periods coincide to avoid fatal outcomes. Dengue is a mosquito-borne viral infection caused by one of the four dengue viruses (DENV-1 to 4). Each of these viruses is capable of causing nonspecific febrile illnesses, classic dengue fever and dengue haemorrhagic fever (Gubler 1998). As a result, dengue is often difficult to diagnose clinically, especially because peak dengue season often coincides with that of other common febrile illnesses in tropical regions (Chacon et al. 2015). In April 2009, a new virus, influenza A/H1N1/pandemic (FluA/H1N1/09pdm), caused a severe outbreak in Mexico. The virus quickly spread throughout the world, and in June 2009, the World Health Organization declared a pandemic (WHO 2010). In Brazil, the first laboratory confirmed case of FluA/H1N1/09pdm was in July 2009 (Pires Neto et al. 2013). The state of Ceará, in Northeast Brazil, is a dengue endemic area. In this state, the virus influenza A(H1N1)pdm09 has circulated since 2009, and through the first half of 2012, 11 deaths caused by the virus were confirmed (Pires Neto et al. 2013). The influenza and dengue seasons in Ceará overlap, which led to diagnostic difficulties. We report four cases of laboratory-confirmed coinfection of deadly influenza A(H1N1)pdm09 with DENV, which occurred during the dengue and influenza season in 2012 and 2013 in Ceará.

  16. Haemagglutinin and nucleoprotein replicon particle vaccination of swine protects against the pandemic H1N1 2009 virus.

    Science.gov (United States)

    Vander Veen, R L; Mogler, M A; Russell, B J; Loynachan, A T; Harris, D L H; Kamrud, K I

    2013-10-12

    The recent emergence of the pandemic H1N1 (pH1N1) and H3N2 variant influenza A viruses (IAV) in 2009 and 2011-2012, respectively, highlight the zoonotic potential of influenza viruses and the need for vaccines capable of eliciting heterosubtypic protection. In these studies, single-cycle, propagation-defective replicon particle (RP) vaccines expressing IAV haemagglutinin (HA) and nucleoprotein (NP) genes were constructed and efficacy was evaluated in homologous and heterologous pig challenge studies with the pH1N1 2009 influenza virus (A/California/04/2009). Homologous HA RP vaccination eliminated virus shedding and decreased pulmonary pathology in pigs following pH1N1 2009 challenge. An RP vaccine expressing an H3N2-derived NP gene was able to decrease nasal shedding and viral load following heterosubtypic pH1N1 2009 challenge in pigs. These studies indicate that although homologous vaccination of swine remains the most effective means of preventing IAV infection, other vaccine alternatives do offer a level of heterosubtypic protection, and should continue to be evaluated for their ability to provide broader protection.

  17. Persistence of pandemic influenza H1N1 virus in young patients after oseltamivir therapy in the 2009-2010 season: a comparison with seasonal H1N1 with or without H275Y mutation.

    Science.gov (United States)

    Kawai, Naoki; Ikematsu, Hideyuki; Iwaki, Norio; Kondou, Kunio; Hirotsu, Nobuo; Kawashima, Takashi; Maeda, Tetsunari; Tanaka, Osame; Doniwa, Ken-ichi; Iwakuni, Osamu; Egashira, Keisuke; Yamaji, Kouzaburo; Kashiwagi, Seizaburo

    2012-04-01

    Comparison of the viral persistence of pandemic H1N1 (H1N1pdm) and seasonal H1N1 with or without H275Y mutation after oseltamivir therapy has not been adequately done. Virus was isolated before and on days 4-6 from the start of oseltamivir treatment for 158 cases of seasonal (2007-2008 and 2008-2009 seasons) or pandemic (2009-2010 season) H1N1 influenza. Sequence analysis was done for each season and NA inhibition assay (IC(50)) was done in the 2009-2010 season. H275Y mutation before therapy was 0% in the 2007-2008 and 2009-2010 seasons, but 100% in the 2008-2009 season. Fever and other symptoms were noticeably prolonged after oseltamivir therapy for children with H275Y mutated seasonal H1N1 (2008-2009 season), but not in patients with seasonal H1N1 without mutation (2007-2008) or H1N1pdm (2009-2010). The viral persistence rate was significantly higher for patients 15 years or younger than for those 16 years and older with H275Y mutated seasonal H1N1 (46.2% and 10.5%, respectively) or with H1N1pdm (43.3% and 11.5%, respectively). The H275Y mutation emerged after oseltamivir treatment in 2.4% (2/82) of all patients with H1N1pdm. In two children, the H275Y mutation emerged after therapy and the IC(50) increased more than 200 fold; however, the prolongation of fever was not so prominent. In conclusion, oseltamivir was effective for fever and other clinical symptoms; however, the virus persisted longer than expected after treatment in H1N1pdm influenza-infected children in the 2009-2010 season, similar to seasonal H1N1 with H275Y mutation in the 2008-2009 season.

  18. Coinfection with influenza A(H1N1pdm09 and dengue virus in fatal cases

    Directory of Open Access Journals (Sweden)

    Anne Carolinne Bezerra Perdigão

    2016-01-01

    Full Text Available Abstract We report on four patients with fatal influenza A(H1N1pdm09 and dengue virus coinfections. Clinical, necropsy and histopathologic findings presented in all cases were characteristic of influenza-dengue coinfections, and all were laboratory-confirmed for both infections. The possibility of influenza and dengue coinfection should be considered in locations where these two viruses’ epidemic periods coincide to avoid fatal outcomes. Dengue is a mosquito-borne viral infection caused by one of the four dengue viruses (DENV-1 to 4. Each of these viruses is capable of causing nonspecific febrile illnesses, classic dengue fever and dengue haemorrhagic fever (Gubler 1998. As a result, dengue is often difficult to diagnose clinically, especially because peak dengue season often coincides with that of other common febrile illnesses in tropical regions (Chacon et al. 2015. In April 2009, a new virus, influenza A/H1N1/pandemic (FluA/H1N1/09pdm, caused a severe outbreak in Mexico. The virus quickly spread throughout the world, and in June 2009, the World Health Organization declared a pandemic (WHO 2010. In Brazil, the first laboratory confirmed case of FluA/H1N1/09pdm was in July 2009 (Pires Neto et al. 2013. The state of Ceará, in Northeast Brazil, is a dengue endemic area. In this state, the virus influenza A(H1N1pdm09 has circulated since 2009, and through the first half of 2012, 11 deaths caused by the virus were confirmed (Pires Neto et al. 2013. The influenza and dengue seasons in Ceará overlap, which led to diagnostic difficulties. We report four cases of laboratory-confirmed coinfection of deadly influenza A(H1N1pdm09 with DENV, which occurred during the dengue and influenza season in 2012 and 2013 in Ceará.

  19. Coinfection with influenza A(H1N1)pdm09 and dengue virus in fatal cases

    Science.gov (United States)

    Perdigão, Anne Carolinne Bezerra; Ramalho, Izabel Letícia Cavalcante; Guedes, Maria Izabel Florindo; Braga, Deborah Nunes Melo; Cavalcanti, Luciano Pamplona Góes; de Melo, Maria Elisabeth Lisboa; Araújo, Rafael Montenegro de Carvalho; Lima, Elza Gadelha; da Silva, Luciene Alexandre Bié; Araújo, Lia de Carvalho; Araújo, Fernanda Montenegro de Carvalho

    2016-01-01

    Abstract We report on four patients with fatal influenza A(H1N1)pdm09 and dengue virus coinfections. Clinical, necropsy and histopathologic findings presented in all cases were characteristic of influenza-dengue coinfections, and all were laboratory-confirmed for both infections. The possibility of influenza and dengue coinfection should be considered in locations where these two viruses’ epidemic periods coincide to avoid fatal outcomes. Dengue is a mosquito-borne viral infection caused by one of the four dengue viruses (DENV-1 to 4). Each of these viruses is capable of causing nonspecific febrile illnesses, classic dengue fever and dengue haemorrhagic fever (Gubler 1998). As a result, dengue is often difficult to diagnose clinically, especially because peak dengue season often coincides with that of other common febrile illnesses in tropical regions (Chacon et al. 2015). In April 2009, a new virus, influenza A/H1N1/pandemic (FluA/H1N1/09pdm), caused a severe outbreak in Mexico. The virus quickly spread throughout the world, and in June 2009, the World Health Organization declared a pandemic (WHO 2010). In Brazil, the first laboratory confirmed case of FluA/H1N1/09pdm was in July 2009 (Pires Neto et al. 2013). The state of Ceará, in Northeast Brazil, is a dengue endemic area. In this state, the virus influenza A(H1N1)pdm09 has circulated since 2009, and through the first half of 2012, 11 deaths caused by the virus were confirmed (Pires Neto et al. 2013). The influenza and dengue seasons in Ceará overlap, which led to diagnostic difficulties. We report four cases of laboratory-confirmed coinfection of deadly influenza A(H1N1)pdm09 with DENV, which occurred during the dengue and influenza season in 2012 and 2013 in Ceará. PMID:27598244

  20. Efficacy of a high-growth reassortant H1N1 influenza virus vaccine against the classical swine H1N1 subtype influenza virus in mice and pigs.

    Science.gov (United States)

    Wen, Feng; Yu, Hai; Yang, Fu-Ru; Huang, Meng; Yang, Sheng; Zhou, Yan-Jun; Li, Ze-Jun; Tong, Guang-Zhi

    2014-11-01

    Swine influenza (SI) is an acute, highly contagious respiratory disease caused by swine influenza A viruses (SwIVs), and it poses a potential global threat to human health. Classical H1N1 (cH1N1) SwIVs are still circulating and remain the predominant subtype in the swine population in China. In this study, a high-growth reassortant virus (GD/PR8) harboring the hemagglutinin (HA) and neuraminidase (NA) genes from a novel cH1N1 isolate in China, A/Swine/Guangdong/1/2011 (GD/11) and six internal genes from the high-growth A/Puerto Rico/8/34(PR8) virus was generated by plasmid-based reverse genetics and tested as a candidate seed virus for the preparation of an inactivated vaccine. The protective efficacy of this vaccine was evaluated in mice and pigs challenged with GD/11 virus. Prime and boost inoculation of GD/PR8 vaccine yielded high-titer serum hemagglutination inhibiting (HI) antibodies and IgG antibodies for GD/11 in both mice and pigs. Complete protection of mice and pigs against cH1N1 SIV challenge was observed, with significantly fewer lung lesions and reduced viral shedding in vaccine-inoculated animals compared with unvaccinated control animals. Our data demonstrated that the GD/PR8 may serve as the seed virus for a promising SwIVs vaccine to protect the swine population.

  1. Simple, rapid detection of influenza A (H1N1) viruses using a highly sensitive peptide-based molecular beacon.

    Science.gov (United States)

    Lim, Eun-Kyung; Guk, Kyeonghye; Kim, Hyeran; Chung, Bong-Hyun; Jung, Juyeon

    2016-01-01

    A peptide-based molecular beacon (PEP-MB) was prepared for the simple, rapid, and specific detection of H1N1 viruses using a fluorescence resonance energy transfer (FRET) system. The PEP-MB exhibited minimal fluorescence in its "closed" hairpin structure. However, in the presence of H1N1 viruses, the specific recognition of the hemagglutinin (HA) protein of H1 strains by the PEP-MB causes the beacon to assume an "open" structure that emits strong fluorescence. The PEP-MB could detect H1N1 viruses within 15 min or even 5 min and can exhibit strong fluorescence even at low viral concentrations, with a detection limit of 4 copies.

  2. PLC-γ1 is involved in the inflammatory response induced by influenza A virus H1N1 infection.

    Science.gov (United States)

    Zhu, Liqian; Yuan, Chen; Ding, Xiuyan; Xu, Shuai; Yang, Jiayun; Liang, Yuying; Zhu, Qiyun

    2016-09-01

    We have previously reported that phosphoinositide-specific phospholipase γ1 (PLC-γ1) signaling is activated by influenza virus H1N1 infection and mediates efficient viral entry in human epithelial cells. In this study, we show that H1N1 also activates PLCγ-1 signaling in human promonocytic cell line -derived macrophages. Surprisingly, the activated PLCγ-1 signaling is not important for viral replication in macrophages, but is involved in the virus-induced inflammatory responses. PLC-γ1-specific inhibitor U73122 strongly inhibits the H1N1 virus-induced NF-κB signaling, blocking the up-regulation of TNF-α, IL-6, MIP-1α, and reactive oxidative species. In a positive feedback loop, IL-1β and TNF-α activate the PLCγ-1 signaling in both epithelial and macrophage cell lines. In summary, we have shown for the first time that the PLCγ-1 signaling plays an important role in the H1N1-induced inflammatory responses. Our study suggests that targeting the PLCγ-1 signaling is a potential antiviral therapy against H1N1 by inhibiting both viral replication and excessive inflammation.

  3. IL-17 response mediates acute lung injury induced by the 2009 Pandemic Influenza A(H1N1)Virus

    Institute of Scientific and Technical Information of China (English)

    Chenggang Li; Chen Wang; Zhongwei Chen; Li Xing; Chong Tang; Xiangwu Ju; Feng Guo; Jiejie Deng; Yan Zhao; Peng Yang; Jun Tang; Penghui Yang; Huanling Wang; Zhongpeng Zhao; Zhinan Yin; Bin Cao; Xiliang Wang; Chengyu Jiang; Yang Sun; Taisheng Li; Chen Wang; Zhong Wang; Zhen Zou; Yiwu Yan; Wei Wang

    2012-01-01

    The 2009 flu pandemic involved the emergence of a new strain of a swine-origin H1N1 influenza virus(S-OIV H1N1)that infected almost every country in the world.Most infections resulted in respiratory illness and some severe cases resulted in acute lung injury.In this report,we are the first to describe a mouse model of S-OIV virus infection with acute lung injury and immune responses that reflect human clinical disease.The clinical efficacy of the antiviral oseltamivir(Tamiflu)administered in the early stages of S-OIV H1N1 infection was confirmed in the mouse model.Moreover,elevated levels of IL-17,Th-17 mediators and IL-17-responsive cytokines were found in serum samples of S-OIV-infected patients in Beijing.IL-17 deficiency or treatment with monoclonal antibodies against IL-17-ameliorated acute lung injury induced by the S-OIV H1N1 virus in mice.These results suggest that IL-17 plays an important role in S-OIV-induced acute lung injury and that monoclonal antibodies against IL-17 could be useful as a potential therapeutic remedy for future S-OIV H1N1 pandemics.

  4. Development of oseltamivir and zanamivir resistance in influenza A(H1N1)pdm09 virus, Denmark, 2014

    DEFF Research Database (Denmark)

    Trebbien, Ramona; Pedersen, Svend Stenvang; Vorborg, Kristine

    2017-01-01

    Antiviral treatment of immunocompromised patients with prolonged influenza virus infection can lead to multidrug resistance. This study reveals the selection of antiviral resistance mutations in influenza A(H1N1)pdm09 virus in an immunocompromised patient during a 6-month period. The patient...

  5. Co-infection of classic swine H1N1 influenza virus in pigs persistently infected with porcine rubulavirus.

    Science.gov (United States)

    Rivera-Benitez, José Francisco; De la Luz-Armendáriz, Jazmín; Saavedra-Montañez, Manuel; Jasso-Escutia, Miguel Ángel; Sánchez-Betancourt, Ivan; Pérez-Torres, Armando; Reyes-Leyva, Julio; Hernández, Jesús; Martínez-Lara, Atalo; Ramírez-Mendoza, Humberto

    2016-02-29

    Porcine rubulavirus (PorPV) and swine influenza virus infection causes respiratory disease in pigs. PorPV persistent infection could facilitate the establishment of secondary infections. The aim of this study was to analyse the pathogenicity of classic swine H1N1 influenza virus (swH1N1) in growing pigs persistently infected with porcine rubulavirus. Conventional six-week-old pigs were intranasally inoculated with PorPV, swH1N1, or PorPV/swH1N1. A mock-infected group was included. The co-infection with swH1N1 was at 44 days post-infection (DPI), right after clinical signs of PorPV infection had stopped. The pigs of the co-infection group presented an increase of clinical signs compared to the simple infection groups. In all infected groups, the most recurrent lung lesion was hyperplasia of the bronchiolar-associated lymphoid tissue and interstitial pneumonia. By means of immunohistochemical evaluation it was possible to demonstrate the presence of the two viral agents infecting simultaneously the bronchiolar epithelium. Viral excretion of PorPV in nasal and oral fluid was recorded at 28 and 52 DPI, respectively. PorPV persisted in several samples from respiratory tissues (RT), secondary lymphoid organs (SLO), and bronchoalveolar lavage fluid (BALF). For swH1N1, the viral excretion in nasal fluids was significantly higher in single-infected swH1N1 pigs than in the co-infected group. However, the co-infection group exhibited an increase in the presence of swH1N1 in RT, SLO, and BALF at two days after co-infection. In conclusion, the results obtained confirm an increase in the clinical signs of infection, and PorPV was observed to impact the spread of swH1N1 in analysed tissues in the early stage of co-infection, although viral shedding was not enhanced. In the present study, the interaction of swH1N1 infection is demonstrated in pigs persistently infected with PorPV.

  6. Course of pandemic influenza A(H1N1) 2009 virus infection in Dutch patients

    NARCIS (Netherlands)

    Friesema, Ingrid H. M.; Meijer, Adam; van Gageldonk-Lafeber, Arianne B.; van der Lubben, Mariken; van Beek, Janko; Donker, Ge A.; Prins, Jan M.; de Jong, Menno D.; Boskamp, Simone; Isken, Leslie D.; Koopmans, Marion P. G.; van der Sande, Marianne A. B.

    2012-01-01

    The clinical dynamics of influenza A(H1N1) 2009 infections in 61 laboratory-confirmed Dutch cases were examined. An episode lasted a median of 7 5 days of which 2 days included fever. Respiratory symptoms resolved slowly, while systemic symptoms peaked early in the episode and disappeared quickly. S

  7. An analysis of peripheral blood cells in patients with influenza A (H1N1) virus infection or non-H1N1 virus infection%甲型H1N1流感病毒与非甲型H1N1流感病毒患者外周血象的对比分析

    Institute of Scientific and Technical Information of China (English)

    王新华; 邵冬华; 梁国威; 曹清云

    2010-01-01

    目的:对航天中心医院就诊的甲型H1N1流感病毒感染者与非甲型H1N1流感病毒感染者、正常对照者的外周血象进行对比分析,以期为临床的诊断、治疗以及病情监测提供有利的工具.方法:采用RT-PCR的方法对患者是否患甲型H1N1流感进行确认.采用流式细胞技术的方法,利用全血细胞计数仪对甲型H1N1组、非甲型H1N1组患者以及正常对照组外周血象进行对比分析.利用免疫比浊的方法对3组患者外周血中C反应蛋白(CRP)浓度进行比较分析.结果:甲型H1N1组患者中单核细胞百分数阳性百分率占77.1%,非甲型H1N1组患者单核细胞百分数阳性百分率占7.8%.正常对照组单核细胞百分数阳性百分率占6.7%.甲型H1N1组白细胞总数、淋巴细胞百分比以及嗜酸细胞百分比与非甲型H1N1组相比明显降低,但甲型H1N1组中性粒细胞百分比与正常对照组相比明显升高,而单核细胞百分比在甲型H1N1组中显著升高.甲型H1N1组血小板总数、血小板压积与非甲型H1N1组相比降低,而血小板分布宽度相比非甲型H1N1组数值升高,但与正常对照组相比,血小板总数以及3项参数未有明显差异.甲型H1N1组中CRP浓度与非甲型H1N1组相比差异无显著性,但与正常对照组相比明显升高.结论:甲型H1N1感染患者外周血象与一般流感存在相似之处,但它有其独特特点,在诊断过程中不应该以一般流感的外周血象以及CRP浓度特点来排除甲型H1N1流感病毒的感染.

  8. Genetic makeup of amantadine-resistant and oseltamivir-resistant human influenza A/H1N1 viruses.

    Science.gov (United States)

    Zaraket, Hassan; Saito, Reiko; Suzuki, Yasushi; Baranovich, Tatiana; Dapat, Clyde; Caperig-Dapat, Isolde; Suzuki, Hiroshi

    2010-04-01

    The emergence and widespread occurrence of antiviral drug-resistant seasonal human influenza A viruses, especially oseltamivir-resistant A/H1N1 virus, are major concerns. To understand the genetic background of antiviral drug-resistant A/H1N1 viruses, we performed full genome sequencing of prepandemic A/H1N1 strains. Seasonal influenza A/H1N1 viruses, including antiviral-susceptible viruses, amantadine-resistant viruses, and oseltamivir-resistant viruses, obtained from several areas in Japan during the 2007-2008 and 2008-2009 influenza seasons were analyzed. Sequencing of the full genomes of these viruses was performed, and the phylogenetic relationships among the sequences of each individual genome segment were inferred. Reference genome sequences from the Influenza Virus Resource database were included to determine the closest ancestor for each segment. Phylogenetic analysis revealed that the oseltamivir-resistant strain evolved from a reassortant oseltamivir-susceptible strain (clade 2B) which circulated in the 2007-2008 season by acquiring the H275Y resistance-conferring mutation in the NA gene. The oseltamivir-resistant lineage (corresponding to the Northern European resistant lineage) represented 100% of the H1N1 isolates from the 2008-2009 season and further acquired at least one mutation in each of the polymerase basic protein 2 (PB2), polymerase basic protein 1 (PB1), hemagglutinin (HA), and neuraminidase (NA) genes. Therefore, a reassortment event involving two distinct oseltamivir-susceptible lineages, followed by the H275Y substitution in the NA gene and other mutations elsewhere in the genome, contributed to the emergence of the oseltamivir-resistant lineage. In contrast, amantadine-resistant viruses from the 2007-2008 season distinctly clustered in clade 2C and were characterized by extensive amino acid substitutions across their genomes, suggesting that a fitness gap among its genetic components might have driven these mutations to maintain it in the

  9. Computational 3D structures of drug-targeting proteins in the 2009-H1N1 influenza A virus

    Science.gov (United States)

    Du, Qi-Shi; Wang, Shu-Qing; Huang, Ri-Bo; Chou, Kuo-Chen

    2010-01-01

    The neuraminidase (NA) and M2 proton channel of influenza virus are the drug-targeting proteins, based on which several drugs were developed. However these once powerful drugs encountered drug-resistant problem to the H5N1 and H1N1 flu. To address this problem, the computational 3D structures of NA and M2 proteins of 2009-H1N1 influenza virus were built using the molecular modeling technique and computational chemistry method. Based on the models the structure features of NA and M2 proteins were analyzed, the docking structures of drug-protein complexes were computed, and the residue mutations were annotated. The results may help to solve the drug-resistant problem and stimulate designing more effective drugs against 2009-H1N1 influenza pandemic.

  10. Influenza virus H1N1 induced apoptosis of mouse astrocytes and the effect on protein expression

    Institute of Scientific and Technical Information of China (English)

    Xu-Dong Pei; Yu-Feng Zhai; Huai-Hong Zhang

    2014-01-01

    Objective:To investigate the effects of influenzaA virusH1N1 infection on the proliferation and apoptosis of mouse astrocytes cells and its protein expression.Methods:After mouse astrocytes was infected with purified influenzaA virusH1N1 in vitro, viral integration and replication status of the cells were detected byRT-PCR assay, cell proliferation and apoptosis was determined by MTT method and flow cytometry, respectively.Associated protein expression was detected by Western blotting.Results:Agarose gel electrophoresis showedH1N1 virus can infect astrocytes and can be copied.MTT staining showedH1N1 virus infection can inhibit the proliferation of mouse astrocytes, which makes cell viability decreased significantly.Flow cytometry showed that the proportion ofAnneinV staining positive vascular endothelial cells in the influenzaA virus group was significantly higher than that in the control group.Western blot analysis showed after 24 h and32 h of infection, there were cells caspase-3 protein and the expression of its active form (lysed caspase-3 protein) increased.The proportion ofBax/Bcl-2 also increased.Conclusions:InfluenzaA virus can infect human vascular endothelial cells and proliferation and it can induce apoptosis of endothelial cells.

  11. [Clinical analysis of 8 children with plastic bronchitis associated with influenza A virus (H1N1) infection].

    Science.gov (United States)

    Zheng, Yue-jie; Deng, Ji-kui; Lu, Zhi-wei; Ma, Hong-ling; Li, Jing; Wang, Li

    2012-07-01

    To analyze the clinical characteristics of plastic bronchitis associated with 2009 influenza A virus (H1N1) infection. A retrospective investigation of the clinical manifestation, bronchoscopy, and the histology of the cast, clinical course and outcome of 8 children with plastic bronchitis associated with influenza A virus (H1N1) infection during winter of 2009 and 2010 was performed. All 8 cases were boys, the range of age was 3 to 6 years. Five cases occurred in 2009 winter, accounting for 3.3% (5/150) of hospitalized children with influenza A (H1N1) infection; 3 cases occurred in 2010 winter, accounting for 15.8% (3/19) of hospitalized children with influenza A (H1N1) infection. Two patients had an underlying chronic disease, 1 had asthma, and the other had allergic rhinitis and atopic dermatitis. All the 8 cases had fever, cough and sputum; 2 had wheezing; 5 had respiratory distress. All 8 cases were diagnosed as influenza A virus (H1N1) infection complicated with pneumonia, of whom 5 patients had atelectasis, 2 had pneumothorax, 1 had pneumomediastinum, 1 had parapneumonic effusion, 2 patients were suspected of foreign body aspiration. Seven cases were admitted to an ICU, 5 patients developed respiratory failure, and 3 patients required mechanical ventilation. Flexible bronchoscopy and bronchial lavage was performed in all cases and showed bronchial cast. Histological examination of the bronchial cast revealed a fibrinous material containing large quantity of eosinophils, neutrophils, and lymphocytes in 7 patients, fibrinous material and necrotic material without inflammatory cells in 1 patient. After the bronchial cast was removed, all patients were improved greatly, no patients died. Plastic bronchitis is a life-threatening complication associated with 2009 influenza A (H1N1) virus infection in children. In children with rapid and progressive respiratory distress with lung atelectasis or consolidation on chest radiograph, plastic bronchitis should be

  12. Vaccination with a soluble recombinant hemagglutinin trimer protects pigs against a challenge with pandemic (H1N1) 2009 influenza virus to high titres

    NARCIS (Netherlands)

    Loeffen, W.L.A.; Vries, de R.P.; Stockhofe, N.; Zoelen-Bos, van D.J.; Maas, H.A.; Koch, G.; Moormann, R.J.M.; Rottier, P.J.M.; Haan, de C.A.M.

    2011-01-01

    In 2009 a new influenza A/H1N1 virus strain (“pandemic (H1N1) 2009”, H1N1v) emerged that rapidly spread around the world. The virus is suspected to have originated in swine through reassortment and to have subsequently crossed the species-barrier towards humans. Several cases of reintroduction into

  13. Epidemiological survey on pandemic influenza A (H1N1) virus infection in Kurdistan province, Islamic Republic of Iran, 2009.

    Science.gov (United States)

    Afrasiabian, S; Mohsenpour, B; Bagheri, K H; Barari, M; Ghaderi, E; Hashemi, R; Garibi, F

    2014-04-03

    This study evaluated the epidemiology of suspected cases of pandemic influenza A (H1N1) virus infection in 2009-2010 in Kurdistan province, a frontier province of the Islamic Republic of Iran. A questionnaire covering demographic characteristics, clinical presentation and outcome, and history of exposure and travel was completed by patients attending health centres and hospitals in the province. Nasal and throat swabs were analysed by RT-PCR. A total of 1059 suspected cases were assessed; H1N1 influenza A was confirmed in 157 (14.8%). The highest proportion of confirmed cases was 30.0%, among children aged Kurdistan.

  14. Information Needs and Seeking Behavior During the H1N1 Virus Outbreak

    Directory of Open Access Journals (Sweden)

    Majid, Shaheen

    2013-03-01

    Full Text Available Timely access to quality healthcare information during an outbreak plays an important role in curtailing its spread. The aim of this study was to investigate the information needs and seeking behavior of the general public in Singapore during the H1N1 pandemic. A pre-tested questionnaire was used for data collection. The convenience snowball sampling method was used and 260 working adults and tertiary-level students participated in this study. The most crucial information needs of a majority of the participants were: symptoms of H1N1, causes of the infection, preventive measures, and possible treatments. Data analysis also revealed that mass media such as television, newspapers, and radio were most frequently used for seeking the needed information. The use of human information sources was also quite high while only a small number of the respondents accessed online news and healthcare websites. About three-quarters of the participants indicated that the gathered information helped them to stay vigilant and take necessary precautionary measures. A major problem identified by the participants in using H1N1 information was the lack of understanding of certain terms used in public communications. This paper suggests certain measures for strengthening health information communication during future outbreaks.

  15. Information Needs and Seeking Behavior During the H1N1 Virus Outbreak

    Directory of Open Access Journals (Sweden)

    Nor Ain Rahmat

    2013-03-01

    Full Text Available Timely access to quality healthcare information during an outbreak plays an important role in curtailing its spread. The aim of this study was to investigate the information needs and seeking behavior of the general public in Singapore during the H1N1 pandemic. A pre-tested questionnaire was used for data collection. The convenience snowball sampling method was used and 260 working adults and tertiary-level students participated in this study. The most crucial information needs of a majority of the participants were: symptoms of H1N1, causes of the infection, preventive measures, and possible treatments. Data analysis also revealed that mass media such as television, newspapers, and radio were most frequently used for seeking the needed information. The use of human information sources was also quite high while only a small number of the respondents accessed online news and healthcare websites. About three-quarters of the participants indicated that the gathered information helped them to stay vigilant and take necessary precautionary measures. A major problem identified by the participants in using H1N1 information was the lack of understanding of certain terms used in public communications. This paper suggests certain measures for strengthening health information communication during future outbreaks.

  16. Novel virus influenza A (H1N1sw in South-Eastern France, April-August 2009.

    Directory of Open Access Journals (Sweden)

    Antoine Nougairède

    Full Text Available BACKGROUND: In April 2009, the first cases of pandemic (H1N1-2009 influenza [H1N1sw] virus were detected in France. Virological surveillance was undertaken in reference laboratories of the seven French Defence Zones. METHODOLOGY/PRINCIPAL FINDINGS: We report results of virological analyses performed in the Public Hospitals of Marseille during the first months of the outbreak. (i Nasal swabs were tested using rapid influenza diagnostic test (RIDT and two RT-PCR assays. Epidemiological characteristics of the 99 first suspected cases were analyzed, including detection of influenza virus and 18 other respiratory viruses. During three months, a total of 1,815 patients were tested (including 236 patients infected H1N1sw virus and distribution in age groups and results of RIDT were analyzed. (ii 600 sera received before April 2009 and randomly selected from in-patients were tested by a standard hemagglutination inhibition assay for antibody to the novel H1N1sw virus. (iii One early (May 2009 and one late (July 2009 viral isolates were characterized by sequencing the complete hemagglutinine and neuraminidase genes. (iiii Epidemiological characteristics of a cluster of cases that occurred in July 2009 in a summer camp were analyzed. CONCLUSIONS/SIGNIFICANCE: This study presents new virological and epidemiological data regarding infection by the pandemic A/H1N1 virus in Europe. Distribution in age groups was found to be similar to that previously reported for seasonal H1N1. The first seroprevalence data made available for a European population suggest a previous exposure of individuals over 40 years old to influenza viruses antigenically related to the pandemic (H1N1-2009 virus. Genomic analysis indicates that strains harbouring a new amino-acid pattern in the neuraminidase gene appeared secondarily and tended to supplant the first strains. Finally, in contrast with previous reports, our data support the use of RIDT for the detection of infection in

  17. Influenza A(H1N1) oseltamivir resistant viruses in the Netherlands during the winter 2007/2008.

    NARCIS (Netherlands)

    Dijkstra, F.; Jonges, M.; Beek, R. van; Donker, G.A.; Schellevis, F.G.; Koopmans, M.; Sande, M.A.B. van der; Osterhaus, A.D.M.E.; Boucher, C.A.B.; Rimmelzwaan, G.F.; Meijer, A.

    2011-01-01

    Background: Antiviral susceptibility surveillance in the Netherlands was intensified after the first reports about the emergence of influenza A(H1N1) oseltamivir resistant viruses in Norway in January, 2008. Methods: Within the existing influenza surveillance an additional questionnaire study was pe

  18. Influenza A(H1N1) oseltamivir resistant viruses in the Netherlands during the winter 2007/2008.

    NARCIS (Netherlands)

    Dijkstra, F.; Jonges, M.; Beek, R. van; Donker, G.A.; Schellevis, F.G.; Koopmans, M.; Sande, M.A.B. van der; Osterhaus, A.D.M.E.; Boucher, C.A.B.; Rimmelzwaan, G.F.; Meijer, A.

    2011-01-01

    Background: Antiviral susceptibility surveillance in the Netherlands was intensified after the first reports about the emergence of influenza A(H1N1) oseltamivir resistant viruses in Norway in January, 2008. Methods: Within the existing influenza surveillance an additional questionnaire study was pe

  19. Protection by Face Masks against H1N1 Virus on Trans-Pacific Passenger Aircraft, 2009

    Centers for Disease Control (CDC) Podcasts

    2013-07-10

    Dr. Mike Miller reads an abridged version of the Emerging Infectious Diseases’ article, Protection by Face Masks against H1N1 Virus on Trans-Pacific Passenger Aircraft, 2009.  Created: 7/10/2013 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 7/11/2013.

  20. Integrated microfluidic system for rapid detection of influenza H1N1 virus using a sandwich-based aptamer assay.

    Science.gov (United States)

    Tseng, Yi-Ting; Wang, Chih-Hung; Chang, Chih-Peng; Lee, Gwo-Bin

    2016-08-15

    The rapid spread of influenza-associated H1N1 viruses has caused serious concern in recent years. Therefore, there is an urgent need for the development of automatic, point-of-care devices for rapid diagnosis of the influenza virus. Conventional approaches suffer from several critical issues; notably, they are time-consuming, labor-intensive, and are characterized by relatively low sensitivity. In this work, we present a new approach for fluorescence-based detection of the influenza A H1N1 virus using a sandwich-based aptamer assay that is automatically performed on an integrated microfluidic system. The entire detection process was shortened to 30min using this chip-based system which is much faster than the conventional viral culture method. The limit of detection was significantly improved to 0.032 hemagglutination unit due to the high affinity and high specificity of the H1N1-specific aptamers. The results showed that the two-aptamer microfluidic system had about 10(3) times higher sensitivity than the conventional serological diagnosis. It was demonstrated that the developed microfluidic system may play as a powerful tool in the detection of the H1N1 virus.

  1. Hemophagocytic Lymphohistiocytosis Induced by Severe Pandemic Influenza A (H1N1 2009 Virus Infection: A Case Report

    Directory of Open Access Journals (Sweden)

    Xiang-Yan Zhang

    2011-01-01

    Full Text Available After early outbreaks in North America in April 2009, the pandemic influenza A (H1N1 virus spread rapidly around the world, and even some patients developed certain severe complications. We reported one case of hemophagocytic lymphohistiocytosis (HLH induced by severe pandemic influenza A (H1N1 virus infection. A 17-year-old girl had acute onset of fever, dry cough, rhinorrhea, and sore throat Her family members and close friends also had the similar symptoms. Anti-infection treatment with penicillin was given after 8 days of the onset of symptoms in the local hospital, and her chest radiograph showed consolidation of the left lung. Then, she was sent to the People's Hospital of Guizhou Province in China and endotracheal intubation were underwent on the ninth day for acute hypoxic respiratory failure. She was diagnosed with HLH induced by severe pandemic influenza A (H1N1 2009 virus. Oseltamivir, steroids, immunoglobulin, and plasmapheresis were given immediately after admission. After being treated in the People's Hospital of Guizhou Province for 16 days, she was discharged. This experience shows that HLH may be a life-threatening complication for severe pandemic influenza A (H1N1 2009 virus infection and responds well to therapy.

  2. Aptamers that bind to the hemagglutinin of the recent pandemic influenza virus H1N1 and efficiently inhibit agglutination.

    Science.gov (United States)

    Gopinath, Subash C B; Kumar, Penmetcha K R

    2013-11-01

    Influenza virus hemagglutinin (HA) mediates both receptor (glycan) binding and membrane fusion for cell entry and has been the basis for typing influenza A viruses. In this study we have selected RNA aptamers (D-12 and D-26) that specifically target the HA protein of the recent pandemic influenza virus pdmH1N1 (A/California/07/2009). Among the selected aptamers the D-26 aptamer showed higher affinity for the HA of pdmH1N1 and was able to distinguish HA derived from other sub-types of influenza A viruses. The affinity of the D-26 aptamer was further improved upon incorporation of 2'-fluoropyrimidines to a level of 67 fM. Furthermore, the high affinity D-12 and D-26 aptamers were tested for their ability to interfere with HA-glycan interactions using a chicken red blood cell (RBC) agglutination assay. At a concentration of 200 nM the D-26 aptamer completely abolished the agglutination of RBCs, whereas D-12 only did so at 400 nM. These studies suggest that the selected aptamer D-26 not only has a higher affinity and specificity for the HA of pdmH1N1 but also has a better ability to efficiently interfere with HA-glycan interactions compared with the D-12 aptamer. The D-26 aptamer warrants further study regarding its application in developing topical virucidal products against the pdmH1N1 virus and also in surveillance of the pdmH1N1 influenza virus.

  3. Molecular and phylogenetic analysis of influenza A H1N1 pandemic viruses in Cuba, May 2009 to August 2010.

    Science.gov (United States)

    Ramos, Alexander Piñón; Herrera, Belsy Acosta; Ramírez, Odalys Valdés; García, Amely Arencibia; Jiménez, Mayra Muné; Valdés, Clara Savón; Fernández, Angel Goyenechea; González, Grehete; Fernández, Suset I Oropesa; Báez, Guelsys González; Espinosa, Bárbara Hernández

    2013-07-01

    The influenza A(H1N1)pdm09 virus was detected in Cuba in May 2009. The introduction of a new virus with increased transmissibility into a population makes surveillance of the pandemic strain to the molecular level necessary. The aim of the present study was the molecular and phylogenetic analysis of pandemic influenza A(H1N1)pdm09 strains that circulated in Cuba between May 2009 and August 2010. Seventy clinical samples were included in the study. Nucleotide sequences from the hemagglutinin HA1 region segment were obtained directly from clinical samples. Genetic distances were calculated using MEGA v.5.05. A phylogenetic tree was constructed using MrBayes v.3.1.2 software. Potential N-glycosylation sites were predicted using NetNGlyc server 1.0. The 48 Cuban sequences of influenza A(H1N1)pdm09 obtained were similar to the A/California/07/2009 (H1N1) vaccine strain. Most of the Cuban strains belonged to clade 7. Cuban viruses showed amino acid changes, some of them located at three antigenic sites: Ca, Sa, and Sb. Two dominant mutations were detected: P83S (100%) and S203T (85.7%). Glycosylation site analysis revealed the gain of one site at position 162 in 13 sequences. The findings in this study contribute to our understanding of the progress of the influenza A(H1N1)pdm09 virus, since this virus is at the starting point of its evolution in humans.

  4. Age-related sensitivity and pathological differences in infections by 2009 pandemic influenza A (H1N1 virus

    Directory of Open Access Journals (Sweden)

    Wu Xiaohong

    2011-02-01

    Full Text Available Abstract Background The highly pandemic 2009 influenza A H1N1 virus infection showed distinguished skewed age distribution with majority of infection and death in children and young adults. Although previous exposure to related antigen has been proposed as an explanation, the mechanism of age protection is still unknown. Methods In this study, murine model of different ages were inoculated intranasally with H1N1 (A/Beijing/501/09 virus and the susceptibility and pathological response to 2009 H1N1 infection were investigated. Results Our results showed that the younger mice had higher mortality rate when infected with the same dose of virus and the lethal dose increased with age. Immunohistochemical staining of H1N1 antigens in mice lung indicated infection was in the lower respiratory tract. Most bronchial and bronchiolar epithelial cells in 4-week mice were infected while only a minor percentage of those cells in 6-month and 1-year old mice did. The young mice developed much more severe lung lesions and had higher virus load in lung than the two older groups of mice while older mice formed more inducible bronchus-associated lymphoid tissue in their lungs and more severe damage in spleen. Conclusions These results suggest that young individuals are more sensitive to H1N1 infection and have less protective immune responses than older adults. The age factor should be considered when studying the pathogenesis and transmission of influenza virus and formulating strategies on vaccination and treatment.

  5. Structure and anti-influenza A (H1N1) virus activity of three polysaccharides from Eucheuma denticulatum

    Science.gov (United States)

    Yu, Guangli; Li, Miaomiao; Wang, Wei; Liu, Xin; Zhao, Xiaoliang; Lv, Youjing; Li, Guangsheng; Jiao, Guangling; Zhao, Xia

    2012-12-01

    Three polysaccharides (EW, EH and EA) were prepared from a red alga Eucheuma denticulatum by sequential extraction with cold water, hot water and sodium hydroxide water solution. Their monosaccharide compositions, relative molecular mass and structural characterization were determined by gas chromatography, high performance 1iquid chromatography, fourier transform infrared spectroscopy and nuclear magnetic resonance spectroscopy methods. EW was hybrid ı/κ/ν-carrageenan (70 ı/17κ/13ν-carrabiose), EH was mainly ı-carrageenan, and EA was mainly α-1,4-Glucan (88%) but mixed with small amount of ı-carrageenan (12%). The relative molecular mass of EW, EH and EA was 480, 580 and 510 kDa, respectively. The anti-influenza A (H1N1) virus activity of these three polysaccharides was evaluated using the Madin-Darby canine kidney cells model. EW showed good anti-H1N1 virus activity, its IC50 was 276.5 μg mL-1, and the inhibition rate to H1N1 virus was 52% when its concentration was 250 μg mL-1. The IC50 of ı-carrageenan EH was 366.4 μg mL-1, whereas EA showed lower anti-H1N1 virus activity (IC50>430 μg mL-1). Available data obtained give positive evidence that the hybrid carrageenan EW from Eucheuma denticulatum can be used as potential anti-H1N1 virus inhibitor in future.

  6. Structure and Anti-influenza A (H1N1) Virus Activity of Three Polysaccharides from Eucheuma denticulatum

    Institute of Scientific and Technical Information of China (English)

    YU Guangli; LI Miaomiao; WANG Wei; LIU Xin; ZHAO Xiaoliang; LV Youjing; LI Guangsheng; JIAO Guangling; ZHAO Xia

    2012-01-01

    Three polysaccharides (EW,EH and EA) were prepared from a red alga Eucheuma denticulatum by sequential extraction with cold water,hot water and sodium hydroxide water solution.Their monosaccharide compositions,relative molecular mass and structural characterization were determined by gas chromatography,high performance liquid chromatography,fourier transform infrared spectroscopy and nuclear magnetic resonance spectroscopy methods.EW was hybrid ι/κ/v-carrageenan (70ι/17κ/13v-carrabiose),EH was mainly ι-carrageenan,and EA was mainly α-1,4-Glucan (88%) but mixed with small amount of ι-carrageenan (12%).The relative molecular mass of EW,EH and EA was 480,580 and 510kDa,respectively.The anti-influenza A (H1N1) virus activity of these three polysaccharides was evaluated using the Madin-Darby canine kidney cells model.EW showed good anti-H1N1 virus activity,its IC50 was 276.5 μg mL-1,and the inhibition rate to H1N1 virus was 52% when its concentration was 250 μg mL-1.The IC50 of ι-carrageenan EH was 366.4 μgmL-1,whereas EA showed lower anti-H1N1 virus activity (IC50>430 μgmL-1).Available data obtained give positive evidence that the hybrid carrageenan EW from Eucheuma denticulatum can be used as potential anti-H1N1 virus inhibitor in future.

  7. Porcine mast cells infected with H1N1 influenza virus release histamine and inflammatory cytokines and chemokines.

    Science.gov (United States)

    Lee, In Hong; Kim, Hyun Soo; Seo, Sang Heui

    2017-04-01

    Mast cells reside in many tissues, including the lungs, and might play a role in enhancing influenza virus infections in animals. In this study, we cultured porcine mast cells from porcine bone marrow cells with IL-3 and stem cell factor to study the infectivity and activation of the 2009 pandemic H1N1 influenza virus of swine origin. Porcine mast cells were infected with H1N1 influenza virus, without the subsequent production of infectious viruses but were activated, as indicated by the release of histamines. Inflammatory cytokine- and chemokine-encoding genes, including IL-1α, IL-6, CXCL9, CXCL10, and CXCL11, were upregulated in the infected porcine mast cells. Our results suggest that mast cells could be involved in enhancing influenza-virus-mediated disease in infected animals.

  8. Development of oseltamivir and zanamivir resistance in influenza A(H1N1)pdm09 virus, Denmark, 2014

    DEFF Research Database (Denmark)

    Trebbien, Ramona; Pedersen, Svend Stenvang; Vorborg, Kristine

    2017-01-01

    Antiviral treatment of immunocompromised patients with prolonged influenza virus infection can lead to multidrug resistance. This study reveals the selection of antiviral resistance mutations in influenza A(H1N1)pdm09 virus in an immunocompromised patient during a 6-month period. The patient was ...... for treatment of individual patients as well as for preventive measures to control the development and transmission of antiviral resistant viruses.......Antiviral treatment of immunocompromised patients with prolonged influenza virus infection can lead to multidrug resistance. This study reveals the selection of antiviral resistance mutations in influenza A(H1N1)pdm09 virus in an immunocompromised patient during a 6-month period. The patient...

  9. Substitutions in position 222 of haemagglutinin of pandemic influenza A (H1N1) 2009 viruses in Spain.

    Science.gov (United States)

    Ledesma, Juan; Pozo, Francisco; Pérez Ruiz, Mercedes; Navarro, Jose María; Piñeiro, Luis; Montes, Milagros; Pérez Castro, Sonia; Suárez Fernández, Jonathan; García Costa, Juan; Fernández, Mirian; Galán, Juan Carlos; Cuevas, María Teresa; Casas, Inmaculada; Pérez Breña, Pilar

    2011-05-01

    A change of aspartic acid (D) to glycine (G) at position 222 in the haemagglutinin (HA) protein of pandemic influenza A (H1N1) 2009 viruses was described in Norway on November 2009 with considerable frequency in fatal and severe cases. This change was detected in other countries and was related only with severe disease. Other substitutions to glutamic acid (E) or asparagine (N) at position 222 were detected among pandemic viruses but it is unclear what implications might have in terms of severity. To analyse the appearance of amino acid substitutions at position 222 in the HA protein of circulating viruses in Spain and to determine their relationships with the disease symptoms observed. Pandemic influenza A (H1N1) 2009 viruses detected in respiratory samples of 273 severe and 533 non-severe cases from different Spanish regions were selected for sequencing of a partial segment of HA1 subunit and studied to monitor substitutions at position 222. D222G substitution was only detected in viruses from 14 severe cases (5.12%). D222E was found in viruses from 47 severe (17.21%) and from 52 non-severe cases (9.75%). D222N occurred in viruses from 3 additional severe cases (0.37%). Appearance of D222G and D222E substitution in HA of pandemic influenza A (H1N1) viruses circulating in Spain might be related with severe respiratory disease. Copyright © 2011 Elsevier B.V. All rights reserved.

  10. 64 multidetector CT findings of influenza A (H1N1) virus in patients with hematologic malignancies

    Energy Technology Data Exchange (ETDEWEB)

    El-Badrawy, Adel [Dept. of Radiology, Mansoura Faculty of Medicine, Mansoura (Egypt)], E-mail: adelelbadrawy@hotmail.com; Zeidan, Amany [Dept. of Thoracic Medicine, Mansoura Faculty of Medicine, Mansoura (Egypt); Ebrahim, Mohamed A. [Dept. of Medical Oncology, Mansoura Faculty of Medicine, Mansoura (Egypt)

    2012-07-15

    Background. The pandemic of swine-origin H1N1 influenza that began in early 2009 has provided evidence that radiology can assist in the early diagnosis of severe cases. Immunocompromised patients are at increased risk for morbidity and mortality. MDCT is superior to radiography in showing the distribution of the disease. Purpose. To review the 64 multidetector CT thoracic findings of novel swine-origin influenza A (H1N1) virus in patients with hematologic malignancies. Material and Methods. This study included 12 patients (3 women, 9 men; mean age, 32.2 years). All patients proved to be infected with influenza A (H1N1) virus. The hematologic malignancies were acute myeloid leukemia (n = 8), chronic lymphocytic leukemia (n = 2), multiple myeloma (n = 1), and myelodysplastic syndrome (n = 1). All the patients underwent CT scanning using a 64 multidetector CT scanner. Chest CT scans were reviewed for ground-glass opacities (GGOs), consolidation, airway thickening/dilatation, nodules, mediastinal lymphadenopathy, and pleural effusion. Results. More than one CT finding was detected in every patient. Pulmonary affection was bilateral, more on the left side. The affections were mainly peribronchial. Airway wall thickening and dilatation were detected in all 12 patients, GGO in 9/12 patients, nodules in 6/12 patients, consolidation in 6/12 patients, hilar lymphadenopathy in 3/12 patients, and pleural effusion in 2/12 patients. Conclusion. Acute myeloid leukemia is the most common hematologic malignancy affected by influenza A (H1N1) virus. The left lung is affected more than the right one. The most common multidetector CT findings are unilateral or bilateral airway thickening and dilatation. Multidetector CT can be used for early and accurate assessment of pulmonary affection with influenza A H1N1 virus infection.

  11. Specific Inhibitory Effect of κ-Carrageenan Polysaccharide on Swine Pandemic 2009 H1N1 Influenza Virus.

    Science.gov (United States)

    Shao, Qiang; Guo, Qiang; Xu, Wen ping; Li, Zandong; Zhao, Tong tong

    2015-01-01

    The 2009 influenza A H1N1 pandemic placed unprecedented demands on antiviral drug resources and the vaccine industry. Carrageenan, an extractive of red algae, has been proven to inhibit infection and multiplication of various enveloped viruses. The aim of this study was to examine the ability of κ-carrageenan to inhibit swine pandemic 2009 H1N1 influenza virus to gain an understanding of antiviral ability of κ-carrageenan. It was here demonstrated that κ-carrageenan had no cytotoxicity at concentrations below 1000 μg/ml. Hemagglutination, 50% tissue culture infectious dose (TCID50) and cytopathic effect (CPE) inhibition assays showed that κ-carrageenan inhibited A/Swine/Shandong/731/2009 H1N1 (SW731) and A/California/04/2009 H1N1 (CA04) replication in a dose-dependent fashion. Mechanism studies show that the inhibition of SW731 multiplication and mRNA expression was maximized when κ-carrageenan was added before or during adsorption. The result of Hemagglutination inhibition assay indicate that κ-carrageenan specifically targeted HA of SW731 and CA04, both of which are pandemic H1N/2009 viruses, without effect on A/Pureto Rico/8/34 H1N1 (PR8), A/WSN/1933 H1N1 (WSN), A/Swine/Beijing/26/2008 H1N1 (SW26), A/Chicken/Shandong/LY/2008 H9N2 (LY08), and A/Chicken/Shandong/ZB/2007 H9N2 (ZB07) viruses. Immunofluorescence assay and Western blot showed that κ-carrageenan also inhibited SW731 protein expression after its internalization into cells. These results suggest that κ-carrageenan can significantly inhibit SW731 replication by interfering with a few replication steps in the SW731 life cycles, including adsorption, transcription, and viral protein expression, especially interactions between HA and cells. In this way, κ-carrageenan might be a suitable alternative approach to therapy meant to address anti-IAV, which contains an HA homologous to that of SW731.

  12. Specific Inhibitory Effect of κ-Carrageenan Polysaccharide on Swine Pandemic 2009 H1N1 Influenza Virus.

    Directory of Open Access Journals (Sweden)

    Qiang Shao

    Full Text Available The 2009 influenza A H1N1 pandemic placed unprecedented demands on antiviral drug resources and the vaccine industry. Carrageenan, an extractive of red algae, has been proven to inhibit infection and multiplication of various enveloped viruses. The aim of this study was to examine the ability of κ-carrageenan to inhibit swine pandemic 2009 H1N1 influenza virus to gain an understanding of antiviral ability of κ-carrageenan. It was here demonstrated that κ-carrageenan had no cytotoxicity at concentrations below 1000 μg/ml. Hemagglutination, 50% tissue culture infectious dose (TCID50 and cytopathic effect (CPE inhibition assays showed that κ-carrageenan inhibited A/Swine/Shandong/731/2009 H1N1 (SW731 and A/California/04/2009 H1N1 (CA04 replication in a dose-dependent fashion. Mechanism studies show that the inhibition of SW731 multiplication and mRNA expression was maximized when κ-carrageenan was added before or during adsorption. The result of Hemagglutination inhibition assay indicate that κ-carrageenan specifically targeted HA of SW731 and CA04, both of which are pandemic H1N/2009 viruses, without effect on A/Pureto Rico/8/34 H1N1 (PR8, A/WSN/1933 H1N1 (WSN, A/Swine/Beijing/26/2008 H1N1 (SW26, A/Chicken/Shandong/LY/2008 H9N2 (LY08, and A/Chicken/Shandong/ZB/2007 H9N2 (ZB07 viruses. Immunofluorescence assay and Western blot showed that κ-carrageenan also inhibited SW731 protein expression after its internalization into cells. These results suggest that κ-carrageenan can significantly inhibit SW731 replication by interfering with a few replication steps in the SW731 life cycles, including adsorption, transcription, and viral protein expression, especially interactions between HA and cells. In this way, κ-carrageenan might be a suitable alternative approach to therapy meant to address anti-IAV, which contains an HA homologous to that of SW731.

  13. Structure modeling and spatial epitope analysis for HA protein of the novel H1N1 influenza virus

    Institute of Scientific and Technical Information of China (English)

    WU Di; XU TianLei; SUN Jing; DAI JianXin; DING GuoHui; HE YunGang; ZHOU ZhengFeng; XIONG Hui; DONG Hui; JIN WeiRong; BIAN Chao; JIN Li; WANG HongYan; WANG XiaoNing; YANG Zhong; ZHONG Yang; WANG Hao; CHE XiaoYan; HUANG Zhong; LAN Ke; SUN Bing; WU Fan; YUAN ZhenAn; ZHANG Xi; ZHOU XiaoNong; ZHOU JiaHai; MA ZhiYong; TONG GuangZhi; GUO YaJun; ZHAO GuoPing; LI YiXue; CAO ZhiWei

    2009-01-01

    In recent months,a novel influenza virus H1N1 broke out around the world.With bioinformatics technology,the 3D structure of HA protein was obtained,and the epitope residues were predicted with the method developed in our group for this novel flu virus.58 amino acids were identified as potential epitope residues,the majority of which clustered at the surface of the globular head of HA protein.Although it is located at the similar position,the epitope of HA protein for the novel H1N1 flu virus has obvious differences in the electrostatic potential compared to that of HA proteins from previous flu viruses.

  14. Acute phase protein response during subclinical infection of pigs with H1N1 swine influenza virus.

    Science.gov (United States)

    Pomorska-Mól, Małgorzata; Markowska-Daniel, Iwona; Pejsak, Zygmunt

    2012-10-12

    In the present study acute phase proteins (APPs) responses in pigs after subclinical infection with H1N1 swine influenza virus (SwH1N1) were evaluated. Fourteen 5 weeks old, seronegative piglets, both sexes were used. Ten of them were infected intranasally with SwH1N1. C-reactive protein (CRP), haptoglobin (Hp), serum amyloid A (SAA) and pig major acute phase protein (Pig-MAP) concentrations in serum were measured using commercial ELISAs. No significant clinical signs were observed in any of the infected pigs, however, all infected animals developed specific antibodies against SwH1N1 and viral shedding was observed from 2 to 5 dpi. Only concentrations of Hp and SAA were significantly induced after infection, with mean maximum levels from days 1 to 2 post infection (dpi). The concentrations of CRP and Pig-MAP remained generally unchanged, however in half of infected pigs the concentration of CRP tended to increase at 1 dpi (but without statistical significance). The results of our study confirmed that monitoring of APPs may be useful for detection of subclinically infected pigs. The use of SAA or Hp and Pig-MAP may be a valuable in combination [i.e. Hp (increased concentration) and Pig-MAP (unchanged concentration)] to detect subclinically SIV infected pigs, or to identify pigs actually producing a large amount of virus. Additional studies need to be done in order to confirm these findings.

  15. Virulence-associated substitution D222G in the hemagglutinin of 2009 pandemic influenza A(H1N1) virus affects receptor binding

    NARCIS (Netherlands)

    S. Chutinimitkul (Salin); S. Herfst (Sander); J. Steel (John); A.C. Lowen (Anice); J. Ye (Jian); D.A.J. van Riel (Debby); E.J.A. Schrauwen (Eefje); T.M. Bestebroer (Theo); B.F. Koel (Björn); D.F. Burke (David); K.H. Sutherland-Cash (Kyle); C.S. Whittleson (Chris); C.A. Russell (Colin); D.J. Wales (David); D.J. Smith (Derek); M. Jonges (Marcel); A. Meijer (Adam); M. Koopmans (Matty); G.F. Rimmelzwaan (Guus); T. Kuiken (Thijs); A.D.M.E. Osterhaus (Albert); A. García-Sastre (Adolfo); D.R. Perez (Daniel); R.A.M. Fouchier (Ron)

    2010-01-01

    textabstractThe clinical impact of the 2009 pandemic influenza A(H1N1) virus (pdmH1N1) has been relatively low. However, amino acid substitution D222G in the hemagglutinin of pdmH1N1 has been associated with cases of severe disease and fatalities. D222G was introduced in a prototype pdmH1N1 by rever

  16. Can breathing circuit filters help prevent the spread of influenza A (H1N1 virus from intubated patients?

    Directory of Open Access Journals (Sweden)

    Heuer, Jan F.

    2013-04-01

    Full Text Available [english] Introduction: In March 2010, more than 213 countries worldwide reported laboratory confirmed cases of influenza H1N1 infections with at least 16,813 deaths. In some countries, roughly 10 to 30% of the hospitalized patients were admitted to the ICU and up to 70% of those required mechanical ventilation. The question now arises whether breathing system filters can prevent virus particles from an infected patient from entering the breathing system and passing through the ventilator into the ambient air.We tested the filters routinely used in our institution for their removal efficacy and efficiency for the influenza virus A H1N1 (A/PR/8/34.Methods: Laboratory investigation of three filters (PALL Ultipor 25, Uor 100 and Pall BB50T Breathing Circuit Filter, manufactured by Pall Life Sciences using a monodispersed aerosol of human influenza A (H1N1 virus in an air stream model with virus particles quantified as cytopathic effects in cultured canine kidney cells (MDCK. Results: The initial viral load of 7.74±0.27 log was reduced to a viral load of ≤2.43 log, behind the filter. This represents a viral filtration efficiency of ≥99.9995%. Conclusion: The three tested filters retained the virus input, indicating that their use in the breathing systems of intubated and mechanically ventilated patients can reduce the risk of spreading the virus to the breathing system and the ambient air.

  17. Reassortment ability of the 2009 pandemic H1N1 influenza virus with circulating human and avian influenza viruses: public health risk implications.

    Science.gov (United States)

    Stincarelli, Maria; Arvia, Rosaria; De Marco, Maria Alessandra; Clausi, Valeria; Corcioli, Fabiana; Cotti, Claudia; Delogu, Mauro; Donatelli, Isabella; Azzi, Alberta; Giannecchini, Simone

    2013-08-01

    Exploring the reassortment ability of the 2009 pandemic H1N1 (A/H1N1pdm09) influenza virus with other circulating human or avian influenza viruses is the main concern related to the generation of more virulent or new variants having implications for public health. After different coinfection experiments in human A549 cells, by using the A/H1N1pdm09 virus plus one of human seasonal influenza viruses of H1N1 and H3N2 subtype or one of H11, H10, H9, H7 and H1 avian influenza viruses, several reassortant viruses were obtained. Among these, the HA of H1N1 was the main segment of human seasonal influenza virus reassorted in the A/H1N1pdm09 virus backbone. Conversely, HA and each of the three polymerase segments, alone or in combination, of the avian influenza viruses mainly reassorted in the A/H1N1pdm09 virus backbone. Of note, A/H1N1pdm09 viruses that reassorted with HA of H1N1 seasonal human or H11N6 avian viruses or carried different combination of avian origin polymerase segments, exerted a higher replication effectiveness than that of the parental viruses. These results confirm that reassortment of the A/H1N1pdm09 with circulating low pathogenic avian influenza viruses should not be misjudged in the prediction of the next pandemic. Copyright © 2013 Elsevier B.V. All rights reserved.

  18. CNS INVOLVEMENT BY NOVEL INFLUENZA VIRUS TYPE A (H1N1, THE FIRST REPORT FROM IRAN

    Directory of Open Access Journals (Sweden)

    Ahad GHAZAVI

    2010-11-01

    Full Text Available AbstractObjectiveThis is the first report of CNS involvement by the new influenza virus (influenza A [H1N1] in Iran. The patient was a 10-year-old boy with chief complaints of fever, malaise, and cranial nerve involvement, resulting in respiratory muscle paralysis and intubation. This shows that the new influenza virus, as well as the seasonal flu, can cause neurologic complications; however, the severity of the signs and symptoms is less and the disease may resolve without complications in the case of seasonal flu. Therefore, in each patient with neurologic involvement and typical influenza signs & symptoms or a flu-like syndrome, diagnostic tests for H1N1 flu virus should be considered, especially during epidemics, and treatment with oseltamivir should be started.

  19. Manifestations of infection by the novel influenza A (H1N1) virus at chest computed tomography; Manifestacoes da infeccao pelo novo virus influenza A (H1N1) na tomografia computadorizada de torax

    Energy Technology Data Exchange (ETDEWEB)

    Verrastro, Carlos Gustavo Yuji; D' Ippolito, Giuseppe [Universidade Federal de Sao Paulo (UNIFESP/EPM), Sao Paulo, SP (Brazil). Dept. de Diagnostico por Imagem], e-mail: giuseppe_dr@uol.com.br; Abreu Junior, Luiz de; Hitomi, Diego Ziotti; Antonio, Emerson Pelarigo [Hospital e Maternidade Sao Luiz, Sao Paulo, SP (Brazil). Servico de Diagnostico por Imagem; Neves, Rodrigo Azambuja [Hospital do Rim e Hipertensao, Sao Paulo, SP (Brazil)

    2009-11-15

    Objective: the objective of this study was to describe chest computed tomography findings in confirmed cases of infection by the novel influenza A (H1N1) virus. Materials and methods: computed tomography studies of nine patients with laboratory-confirmed infection by the novel influenza A (H1N1) virus were consensually evaluated by three observers. The sample of the present study included five male and four female patients with ages ranging from 14 to 64 years (mean, 40 years). Four of the patients were previously healthy, four were kidney transplant recipients and one was pregnant at the time of diagnosis. Presence, extent and distribution of the following findings were evaluated: ground-glass opacities; centrilobular nodules; consolidation; interlobular septa thickening; pleural effusion; lymphadenopathy. Results: The most frequent findings were ground-glass opacities, centrilobular nodules and consolidations, present in nine (100%), five (55%) and four (44%) of cases, respectively. Pleural effusions and lymphadenopathy were less common findings, occurring in only two (22%) of the cases. Conclusion: ground-glass opacities, centrilobular nodules and consolidation were the most frequent findings in cases of infection by the novel influenza A (H1N1) virus. These changes are not typical or unique to this agent and may also occur in other viral or bacterial infections. (author)

  20. A(H1N1)流感病毒及抗病毒新药的筛选%A(H1N1) Influenza Virus and Screening of New Anti-influenza Virus Drugs

    Institute of Scientific and Technical Information of China (English)

    陈执中

    2009-01-01

    A(H1N1) influenza virus is a novel strain of influenza virus mutant,which was found in March to April 2009 in USA and Mexico. The spread of epidemic influenza brings about a serious attention by every country in the world and World Health Organization. In this paper, the A (H1N1) influenza virus and its symptom, virulence and spread are introduced. Meanwhile, the mutant' s resistance to anti-influenza drugs, the characterization of the 1918 pandemic influenza virus polymerase, the crystal structure of human and avian influenza virus polymerase and its action in influenza are also discussed. Accordingly, we put forward the screening ideas and research orientation for anti-influenza virus drugs, which will be a beneficial reference for the further design and development of new anti-influenza virus drugs.%A(H1N1)流感病毒是2009年3~4月在美国和墨西哥发现的一种流感病毒变异的新病毒株.这类流感疫情的蔓延引起了世界各国和世界卫生组织的严重关注.本文介绍了A(H1N1)流感新病毒株及感染这种病毒患者的症状,A(H1N1)流感病毒的致命力和传播,流感病毒变异对抗病毒药的抗药性,以及1918年流感大流行病毒聚合酶特性,人流感病毒和禽流感病毒聚合酶的结晶结构及其在感染中的作用.据此,提出了抗流感病毒药的筛选思路和研究方向,为抗流感病毒新药的设计和开发提供有益的参考.

  1. Seroprotective Titers against 2009 H1N1 Influenza A Virus after Vaccination in Allogeneic Hematopoietic Stem Cell Transplantation Recipients

    Science.gov (United States)

    Issa, Nicolas C.; Marty, Francisco M.; Gagne, Lisa S.; Koo, Sophia; Verrill, Kelly A.; Alyea, Edwin P.; Cutler, Corey S.; Koreth, John; Armand, Philippe; Ho, Vincent T.; Antin, Joseph H.; Soiffer, Robert J.; Baden, Lindsey R.

    2012-01-01

    Little data are available regarding the safety and immunologic response to pandemic H1N1 influenza vaccine in recipients of allogeneic hematopoietic stem cell transplantation (HSCT). We measured serum antibody titers against A/California/7/2009 H1N1 using a hemagglutination inhibition assay in 82 allogeneic HSCT recipients who received the 2009 H1N1 vaccine between November 2009 and January 2010 after it became available at our institution. The median time between HSCT and vaccination was 19 months (range, 2.5–94 months), and the median time from vaccination to specimen collection was 56 days (range, 14–140 days). Seroprotective antibody titers (hemagglutination inhibition titer ≥1:40) against 2009 H1N1 influenza A virus were detected in 51% of patients. The presence of chronic graft-versus-host disease and type of conditioning regimen did not affect the rate of detection of seroprotective titers after vaccination. Patients were more likely to have a seroprotective titer the farther away from HSCT they were (adjusted odds ratio, 1.79 per year; 95% confidence interval, 1.12–2.85). Rituximab administration in the year before vaccination was associated with a lack of seroprotective titer (adjusted odds ratio, 0.11; 95% confidence interval, 0.01–0.97). The vaccine was safe and well tolerated. Strategies are needed to improve the influenza vaccine response in this population, especially those receiving immunotherapy. PMID:20950701

  2. 甲型H1N1流感病毒临床实验室诊断策略%Clinical Laboratory Diagnostic Strategies of Influenza A/H1N1 Virus

    Institute of Scientific and Technical Information of China (English)

    苏明权; 杨柳; 马越云; 郝晓柯

    2011-01-01

    Objective To study a clinical labaratory diagnostic strategy for influenza A/H1N1 patients. Methods To detect the influenza A virus antigen by Dot-ELISA method in influenza patients , initially diagnosed as influenza A or non-influenza; for the influenza A virus antigen-positive patients ,further testing influenza A/H1N1 virus-specific nucleic acid using real-time RT-PCR method. Results For 44.448 cases of influenza patients in xi'an to screened influenza A virus antigen,the positive rate as 28. 25%;further detected influenza A/H1N1 virus nucleic acid for 17 714 cases of antigen-positive patients,the positive rate of 41. 92%.Conclusion First screening the influenza A virus antigen,to exclude non-influenza A virus;and then within the framewark of influenza A virus to detect influenza A/H1N1 virus,that increased the detection efficiency of influenza A viruses,but also reduced the pressure on influenza A/H1N1 virus nucleic acid testing and the economic burden of patients. This detection strategy provided reference for laboratory diagnosis of influenza A/H1N1,and more effective control,diagnose influenza A/H1N1 virus infection.%目的 探讨用于甲型H1N1流感患者临床实验室诊断的策略.方法 采用Dot-ELISA法检测流感患者中的甲型流感病毒的抗原,初步明确为甲型流感或排除非甲型流感;采用real-time RT-PCR法检测甲型流感病毒抗原阳性患者中的甲型H1N1流感病毒特异性核酸,进一步确定甲型H1N1流感病毒.结果 对44 448例在西安地区就诊的发热伴有流感样症状者的鼻咽腔取分泌物进行甲型流感病毒抗原筛查,其阳性筛检率为28.25%;对甲型流感病毒抗原筛查阳性的17 714例患者进行甲型H1N1流感病毒核酸检测,其阳性检出率为41.92%.结论 首先用甲型流感病毒抗原筛查,排除非甲型流感病毒;进而在甲型流感病毒的范围内进行甲型H1N1流感病毒的检测,即加快了甲型流感病毒的排查效率,又减轻了甲型H

  3. Probable transmisión vertical del virus de la influenza A (H1N1: a propósito de un caso Probable vertical transmission of the influenza virus A (H1N1: apropos of a case

    Directory of Open Access Journals (Sweden)

    Rubén D. Vásquez

    2010-09-01

    Full Text Available Se reporta el caso de un recién nacido varón, producto de embarazo de 36 semanas, con diagnóstico de neumonía congénita y examen confirmatorio de infección por el virus de la influenza A (H1N1, sin ningún otro tipo de contacto sospechoso. La madre ingresó al hospital con insuficiencia respiratoria y antecedente de proceso gripal de cinco días de evolución, durante los primeros días de la pandemia en el Perú. Por la evolución grave del proceso respiratorio, se le administró ventilación mecánica para luego ser sometida a cesárea por sufrimiento fetal agudo y oligoamnios. Se confirmó en la madre infección por el virus de la influenza A H1N1 epidémico y tuberculosis pulmonar.We report the case of a male newborn, product of a 36 week pregnancy, with diagnosis of congenital pneumonia and with a confirmatory test for influenza A (H1N1 virus, without any other suspicious contact. The mother was admitted to the hospital with respiratory failure and the history of a flu-like episode of 5 days of evolution, during the first days of the pandemic in Peru. Due to the severe evolution of the respiratory process, assisted ventilation was given to her and then a cesarean section was performed due to acute fetal distress and oligoamnios. The mother was later confirmed as a case of epidemic influenza A (H1N1 and pulmonary tuberculosis.

  4. Recurrent plastic bronchitis in a child with 2009 influenza A (H1N1) and influenza B virus infection.

    Science.gov (United States)

    Kim, Sun; Cho, Hwa Jin; Han, Dong Kyun; Choi, Yoo Duk; Yang, Eun Seok; Cho, Young Kuk; Ma, Jae Sook

    2012-09-01

    Plastic bronchitis is an uncommon disorder characterized by the formation of bronchial casts. It is associated with congenital heart disease or pulmonary disease. In children with underlying conditions such as allergy or asthma, influenza can cause severe plastic bronchitis resulting in respiratory failure. A review of the literature showed nine cases of plastic bronchitis with H1N1 including this case. We report a case of a child with recurrent plastic bronchitis with eosinophilic cast associated with influenza B infection, who had recovered from plastic bronchitis associated with an influenza A (H1N1) virus infection 5 months previously. To the best of our knowledge, this is the first case of recurrent plastic bronchitis related to influenza viral infection. If patients with influenza virus infection manifest acute respiratory distress with total lung atelectasis, clinicians should consider plastic bronchitis and early bronchoscopy should be intervened. In addition, management for underlying disease may prevent from recurrence of plastic bronchitis.

  5. Genetic Characteristics and Immunogenicity of Pandemic H1N1 Influenza Virus Isolate from Pig in Korea

    Science.gov (United States)

    Moon, Hyoung Joon; Oh, Jin Sik; Na, Woonsung; Yeom, Minjoo; Han, Sang Yoon; Kim, Sung Jae; Park, Bong Kyun

    2016-01-01

    A pandemic influenza A (H1N1) virus strain was isolated from a pig farm in Korea in December 2009. The strain was propagated in and isolated from both the Madin-Darby canine kidney cell line and embryonated eggs. The partial and complete sequences of the strain were identical to those of A/California/04/2009, with >99% sequence similarity in the HA, NA, M, NS, NP, PA, PB1, and PB2 genes. The isolated strain was inactivated and used to prepare a swine influenza vaccine. This trial vaccine, containing the new isolate that has high sequence similarity with the pandemic influenza A (H1N1) virus, resulted in seroconversion in Guinea pigs and piglets. This strain could therefore be a potential vaccine candidate for swine influenza control in commercial farms.

  6. The mutation network for the hemagglutinin gene from the novel influenza A (H1N1) virus

    Institute of Scientific and Technical Information of China (English)

    HE YunGang; DING GuoHui; BIAN Chao; HUANG Zhong; LAN Ke; SUN Bing; WANG XueCai; LI YiXue; WANG HongYan; WANG XiaoNing; YANG Zhong; ZHONG Yang; JIN WeiRong; XIONG Hui; DAI JianXin; GUO YaJun; WANG Hao; CHE XiaoYan; WU Fan; YUAN ZhenAn; ZHANG Xi; CAO ZhiWei; ZHOU XiaoNong; ZHOU JiaHai; MA ZhiYong; TONG GuangZhi; ZHAO GuoPing; JIN Li

    2009-01-01

    A mutation network for the hemagglutinin gene (HA) of the novel type A (H1N1) influenza virus was constructed.Sequence homology analysis indicated that one HA sequence type from the viruses mainly isolated from Mexico was likely the original type in this epidemic.Based on the 658A and 1408T mutations in HA,the viruses evolving into this epidemic were divided into three categories,the Mexico,the transitional and the New York type.The three groups of viruses presented distinctive clustering features in their geographic distributions.

  7. Antigenic Drift of the Pandemic 2009 A(H1N1) Influenza Virus in a Ferret Model

    Science.gov (United States)

    Guarnaccia, Teagan; Carolan, Louise A.; Maurer-Stroh, Sebastian; Lee, Raphael T. C.; Job, Emma; Reading, Patrick C.; Petrie, Stephen; McCaw, James M.; McVernon, Jodie; Hurt, Aeron C.; Kelso, Anne; Mosse, Jennifer; Barr, Ian G.; Laurie, Karen L.

    2013-01-01

    Surveillance data indicate that most circulating A(H1N1)pdm09 influenza viruses have remained antigenically similar since they emerged in humans in 2009. However, antigenic drift is likely to occur in the future in response to increasing population immunity induced by infection or vaccination. In this study, sequential passaging of A(H1N1)pdm09 virus by contact transmission through two independent series of suboptimally vaccinated ferrets resulted in selection of variant viruses with an amino acid substitution (N156K, H1 numbering without signal peptide; N159K, H3 numbering without signal peptide; N173K, H1 numbering from first methionine) in a known antigenic site of the viral HA. The N156K HA variant replicated and transmitted efficiently between naïve ferrets and outgrew wildtype virus in vivo in ferrets in the presence and absence of immune pressure. In vitro, in a range of cell culture systems, the N156K variant rapidly adapted, acquiring additional mutations in the viral HA that also potentially affected antigenic properties. The N156K escape mutant was antigenically distinct from wildtype virus as shown by binding of HA-specific antibodies. Glycan binding assays demonstrated the N156K escape mutant had altered receptor binding preferences compared to wildtype virus, which was supported by computational modeling predictions. The N156K substitution, and culture adaptations, have been detected in human A(H1N1)pdm09 viruses with N156K preferentially reported in sequences from original clinical samples rather than cultured isolates. This study demonstrates the ability of the A(H1N1)pdm09 virus to undergo rapid antigenic change to evade a low level vaccine response, while remaining fit in a ferret transmission model of immunization and infection. Furthermore, the potential changes in receptor binding properties that accompany antigenic changes highlight the importance of routine characterization of clinical samples in human A(H1N1)pdm09 influenza surveillance

  8. Research progress of β-defensins and infection of H1N1 virus%β防御素与甲型H1N1流感病毒感染最新研究进展

    Institute of Scientific and Technical Information of China (English)

    李佳佳; 曹彬

    2014-01-01

    流感是影响人类健康的最重要疾病之一.2009年甲型H1N1流感的大流行造成数十万人感染,接近20 000人死亡,研究发现人体的固有免疫影响甲型H1N1流感病毒感染后的严重程度.防御素是近年来发现的一种小分子内源性多肽,它是固有免疫中一种重要组成成分,它不仅可以通过直接杀菌作用抵御细菌、真菌及包膜病毒的入侵,还在介导获得性免疫反应、调节机体的免疫炎症反应和创伤修复过程中起着重要作用.本文结合近几年β防御素的相关研究,就β防御素、甲型H1N1流感病毒感染以及二者免疫关系做简要的综述.%The flu is one of the most serious diseases that affect human health.In 2009,thousands of people infected with pandemic H1N1 virus,closing to twenty thousands people were killed.Recently some study found that after infected with H1N1 the human natural immune affect the severity of the illness.Defensins,a small molecule endogenous peptide,is one of the most important natural immune components.It can fight against bacteria,fungi,and virus directly.Also defensins can mediate acquired immune response,regulate the body's immune inflammation and repaire wound.Based on related researches in recent years,this article briefly reviews β-defensins,H1N1 virus,and the immune relationship between β-defensions and H1N1 virus infection.

  9. [Virological surveillance of pandemic (H1N1) 2009 virus and its genetic characteristics in Hunan Province, 2009-2011].

    Science.gov (United States)

    Zhang, Hong; Huang, Yi-Wei; Liu, Yun-Zhi; Li, Fang-Cai; Chen, Zhang; Li, Wen-Chao; Deng, Zhi-Hong; Hu, Shi-Xiong; Gao, Li-Dong

    2013-03-01

    To understand and master the dynamic variation of the pandemic influenza A (H1N1) 2009 in Hunan province from 2009 to 2011, and to know the genetic characteristics and drug resistance of the pandemic (H1N1) 2009 viruses. Throat swab specimens of influenza-like illness patients were collected from sentinel hospitals and tested for influenza by fluorescent PCR or virus isolation methods. Partial isolates were selected for sequencing. The sequences were used for phylogenetic analysis by MEGA 5. 05 software. From the 20th week of 2009 to the 52nd week of 2011, 17 773 specimens were tested. 3 831 specimens were influenza-positive with a positive rate of 21. 6%, of which 1 794 were positive specimens of pandemic (H1N1) 2009, accounting for 46. 8%00 of the influenza-positives. There were 2 epidemic peaks of pandemic (H1N1) 2009, which were in the 41st-53rd week of 2009 and the 1st-12nd week of 2011, respectively. The HA genes of 23 strains that were selected for sequencing had close relationship; the distribution of strains in the phylogenetic tree was basically in chronological order. The complete genome sequence analysis showed that all of 8 gene segments of 7 strains were homologous to the vaccine strain, and there was no gene reassortment. The HA amino acid sites of the 23 strains were highly similar to the vaccine strain (98. 2% - 100. 0% in homology), but all 23 strains had P83S, S203T and 1321V mutations. The 222 site mutation that may lead to enhanced virulence was found in the A/Hunan/YQ30/2009 strain. The mutation was D222E. There was no oseltamivir resistance mutation found in all strains. The pandemic (H1N1) 2009 in Hunan province from 2009 to 2011 had a bimodal distribution. There was no large-scale variation of virus genes. The clinical use of oseltamivir was still effective. Key words: Pandemic (H1N1) 2009; Surveillance; Genetic characteristics

  10. Antiviral and anti-inflammatory activity of arbidol hydrochloride in influenza A (H1N1) virus infection

    Institute of Scientific and Technical Information of China (English)

    Qiang LIU; Hai-rong XIONG; Li LU; Yuan-yuan LIU; Fan LUO; Wei HOU; Zhan-qiu YANG

    2013-01-01

    Aim:To investigate the effects of arbidol hydrochloride (ARB),a widely used antiviral agent,on the inflammation induced by influenza virus.Methods:MDCK cells were infected with seasonal influenza A/FM/1/47 (H1N1) or pandemic influenza A/Hubei/71/2009 (H1N1).In vitro cytotoxicity and antiviral activity of ARB was determined using MTT assay.BALB/c mice were infected with A/FM/1/47 (H1N1).Four hours later the mice were administered ARB (45,90,and 180 mg·kg-1·d-1) or the neuraminidase inhibitor oseltamivir (22.5mg·kg-1·d-1) via oral gavage once a day for 5 d.Body-weight,median survival time,viral titer,and lung index of the mice were measured.The levels of inflammatory cytokines were examined using real-time RT-PCR and ELISA.Results:Both H1N1 stains were equally sensitive to ARB as tested in vitro.In the infected mice,ARB (90 and 180 mg·kg-1·d-1)significantly decreased the mortality,alleviated virus-induced lung lesions and viral titers.Furthermore,ARB suppressed the levels of IL-1β,IL-6,IL-12,and TNF-α,and elevated the level of IL-10 in the bronchoalveolar lavage fluids and lung tissues.However,ARB did not significantly affect the levels of IFN-α and IFN-γ,but reduced the level of IFN-β1 in lung tissues at 5 dpi.In peritoneal macrophages challenged with A/FM/1/47 (H1N1) or poly I∶C,ARB (20 μmol/L) suppressed the levels of IL-1β,IL-6,IL-12,and TNF-α,and elevated the level of IL-10.Oseltamivir produced comparable alleviation of virus-induced lung lesions with more reduction in the viral titers,but less effective modulation of the inflammatory cytokines.Conclusion:ARB efficiently inhibits both H1N1 stains and diminishes both viral replication and acute inflammation through modulating the expression of inflammatory cytokines.

  11. 2009甲型H1N1流感病毒的研究综述%Review of the 2009 A ( H1N1 ) Influenza Virus

    Institute of Scientific and Technical Information of China (English)

    刘超; 胡春吉; 徐瑞芹

    2011-01-01

    2009年4月初,出现1种新型甲型( H1N1)流感病毒,并通过人—人传播蔓延全球,文章介绍了该病毒的分类与宿主范围,并对其病毒学及分子特征进行了概述,最后指出加强对猪群中流行的流感病毒监管的必要性及研制通用疫苗的重要性.%A novel influenza A/H1N1 virus, emerged in early April 2009. It quickly spread worldwide through human-to-human transmission. The classification and host range of the virus were introduced, and its virdogy and molecular characteristics were described. Then concluded that the necessity of supervision on strengthening pandemic influenza virus in swine and importance of developing common vaccines.

  12. Chest Radiographic Findings of Novel Swine-Origin Influenza A (H1N1) Virus Infection in Children

    Energy Technology Data Exchange (ETDEWEB)

    Bae, So Young; Hong, Eun Sook; Paik, Sang Hyun; Park, Seong Jin; Cha, Jang Gyu; Lee, Hae Kyung [Dept. of Radiology, Soonchunhyang University Bucheon Hospital, Bucheon (Korea, Republic of); Jang, Yun Woo [Dept. of Radiology, Soonchunhyang University Hospital, Seoul (Korea, Republic of)

    2011-06-15

    To analyze chest radiographic findings in children infected with laboratory confirmed novel swine-origin influenza A (H1N1) virus. Three hundred seventy-two out of 2,014 children with laboratory confirmed H1N1 infection and who also underwent a chest radiograph from September to November 2009 were enrolled in this study. Patients were divided into in-patients, out-patients, and patients with co-infections and further subdivided into with underlying disease and without underlying disease as well as age (<2 years old, 2-5 years, 5-10 years, 10-18 years old). The initial radiographs were evaluated for radiographic findings and the anatomic distribution of abnormalities. The initial radiographs were abnormal in 154 (41.39%) patients. The predominant radiographic findings were peribronchial wall opacity found in 85 (22.84%) patients and hyperinflation observed in 69 (18.54%) patients. Further, 75 (71.42%) patients exhibited central predominance and the right lower lung zone was also commonly involved. There were statistically significant differences in the radiological findings between in-patient and out-patient groups. However, there were no significant differences in the radiographic findings between in-patients and the co-infection group with respect the presence of underlying disease and age. Initial radiographs of children with laboratory confirmed H1N1 virus were abnormal in 41.39% of cases. The common radiographic findings included peribronchial opacities, hyperinflation, lower lung zonal distribution, and central predominance

  13. Radiological and Clinical Characteristics of a Military Outbreak of Pandemic H1N1 2009 Influenza Virus Infection

    Energy Technology Data Exchange (ETDEWEB)

    Yun, Tae Jin; Kwon, Gu Jin; Oh, Mi Kyeong; Woo, Sung Koo; Park, Seung Hoon; Choi, Seung Hong; Lee, Hyun Ju; Goo, Jin Mo; Yim, Jae Joon; Kim, Jong Sung; Park, Chang Min [Seoul National University Hospital, Seoul (Korea, Republic of)

    2010-08-15

    To describe detailed clinical and radiological features of the pandemic H1N1 2009 influenza viral infection among healthy young males in a semiclosed institutionalized setting. A total of 18 patients confirmed with the pandemic H1N1 2009 influenza virus infection from July 18 to July 30, 2009 were enrolled in this study. Each patient underwent an evaluation to determine detailed clinical and radiological features. All patients presented with high fever (> 38.0..C), with accompanying symptoms of cough, rhinorrhea, sore throat, myalgia and diarrhea, and increased C-reactive protein (CRP) values with no leukocytosis nor elevated erythrocyte sedimentation rate (ESR). All patients, including one patient who progressed into acute respiratory distress syndrome, were treated with oseltamivir phosphate and quickly recovered from their symptoms. Chest radiographs showed abnormalities of small nodules and lobar consolidation in only two out of 18 patients. However, six of 12 patients who underwent thin-section CT examinations showed abnormal findings for small ground-glass opacities (GGOs) in addition to poorly-defined nodules with upper lobe predominance. In a population of healthy young adults, elevated CRP with normal ESR and white blood cell levels combined with GGOs and nodules on thin section CT scans may indicate early signs of infection by the pandemic H1N1 2009 influenza virus

  14. Immunogenicity, boostability, and sustainability of the immune response after vaccination against Influenza A virus (H1N1) 2009 in a healthy population

    NARCIS (Netherlands)

    Huijskens, Elisabeth; Rossen, John; Mulder, Paul; van Beek, Ruud; van Vugt, Hennie; Verbakel, Johannes; Rimmelzwaan, Guus; Koopmans, Marion; Peeters, Marcel

    2011-01-01

    The emergence of a new influenza A virus (H1N1) variant in 2009 led to a worldwide vaccination program, which was prepared in a relatively short period of time. This study investigated the humoral immunity against this virus before and after vaccination with a 2009 influenza A virus (H1N1) monovalen

  15. Antibody-Dependent Cell-Mediated Cytotoxicity Epitopes on the Hemagglutinin Head Region of Pandemic H1N1 Influenza Virus Play Detrimental Roles in H1N1-Infected Mice

    Science.gov (United States)

    Ye, Zi-Wei; Yuan, Shuofeng; Poon, Kwok-Man; Wen, Lei; Yang, Dong; Sun, Zehua; Li, Cun; Hu, Meng; Shuai, Huiping; Zhou, Jie; Zhang, Mei-Yun; Zheng, Bo-Jian; Chu, Hin; Yuen, Kwok-Yung

    2017-01-01

    Engaging the antibody-dependent cell-mediated cytotoxicity (ADCC) for killing of virus-infected cells and secretion of antiviral cytokines and chemokines was incorporated as one of the important features in the design of universal influenza vaccines. However, investigation of the ADCC epitopes on the highly immunogenic influenza hemagglutinin (HA) head region has been rarely reported. In this study, we determined the ADCC and antiviral activities of two putative ADCC epitopes, designated E1 and E2, on the HA head of a pandemic H1N1 influenza virus in vitro and in a lethal mouse model. Our data demonstrated that sera from the E1-vaccinated mice could induce high ADCC activities. Importantly, the induction of ADCC response modestly decreased viral load in the lungs of H1N1-infected mice. However, the elevated ADCC significantly increased mouse alveolar damage and mortality than that of the PBS-vaccinated group (P H1N1 influenza virus challenge. Overall, our data suggested that ADCC elicited by certain domains of HA head region might have a detrimental rather than protective effect during influenza virus infection. Thus, future design of universal influenza vaccine shall strike a balance between the induction of protective immunity and potential side effects of ADCC. PMID:28377769

  16. Mutations in polymerase genes enhanced the virulence of 2009 pandemic H1N1 influenza virus in mice.

    Directory of Open Access Journals (Sweden)

    Wenfei Zhu

    Full Text Available Influenza A virus can infect a wide variety of animal species with illness ranging from mild to severe, and is a continual cause for concern. Genetic mutations that occur either naturally or during viral adaptation in a poorly susceptible host are key mechanisms underlying the evolution and virulence of influenza A virus. Here, the variants containing PA-A36T or PB2-H357N observed in the mouse-adapted descendants of 2009 pandemic H1N1 virus (pH1N1, A/Sichuan/1/2009 (SC, were characterized. Both mutations enhanced polymerase activity in mammalian cells. These effects were confirmed using recombinant SC virus containing polymerase genes with wild type (WT or mutant PA or PB2. The PA-A36T mutant showed enhanced growth property compared to the WT in both human A549 cells and porcine PK15 cells in vitro, without significant effect on viral propagation in murine LA-4 cells and pathogenicity in mice; however, it did enhance the lung virus titer. PB2-H357N variant demonstrated growth ability comparable to the WT in A549 cells, but replicated well in PK15, LA-4 cells and in mice with an enhanced pathogenic phenotype. Despite such mutations are rare in nature, they could be observed in avian H5 and H7 subtype viruses which were currently recognized to pose potential threat to human. Our findings indicated that pH1N1 may adapt well in mammals when acquiring these mutations. Therefore, future molecular epidemiological surveillance should include scrutiny of both markers because of their potential impact on pathogenesis.

  17. Comparative Pathogenesis of an Avian H5N2 and a Swine H1N1 Influenza Virus in Pigs

    DEFF Research Database (Denmark)

    De Vleeschauwer, Annebel; Atanasova, Kalina; Van Borm, Steven

    2009-01-01

    Pigs are considered intermediate hosts for the transmission of avian influenza viruses (AIVs) to humans but the basic organ pathogenesis of AIVs in pigs has been barely studied. We have used 42 four-week-old influenza naive pigs and two different inoculation routes (intranasal and intratracheal......) to compare the pathogenesis of a low pathogenic (LP) H5N2 AIV with that of an H1N1 swine influenza virus. The respiratory tract and selected extra-respiratory tissues were examined for virus replication by titration, immunofluorescence and RT-PCR throughout the course of infection. Both viruses caused...... milder with the avian than with the swine virus, corresponding with lower viral loads in the lungs. The brainstem was the single extra-respiratory tissue found positive for virus and viral RNA with both viruses. Our data do not reject the theory of the pig as an intermediate host for AIVs...

  18. Association of swine influenza H1N1 pandemic virus (SIV-H1N1p) with porcine respiratory disease complex in sows from commercial pig farms in Colombia.

    Science.gov (United States)

    Jiménez, Luisa Fernanda Mancipe; Ramírez Nieto, Gloria; Alfonso, Victor Vera; Correa, Jairo Jaime

    2014-08-01

    Porcine respiratory disease complex (PRDC) is a serious health problem that mainly affects growing and finishing pigs. PRDC is caused by a combination of viral and bacterial agents, such as porcine reproductive and respiratory syndrome virus (PRRSV), swine influenza virus (SIV), Mycoplasma hyopneumoniae (Myh), Actinobacillus pleuropneumoniae (APP), Pasteurella multocida and Porcine circovirus 2 (PCV2). To characterize the specific role of swine influenza virus in PRDC presentation in Colombia, 11 farms from three major production regions in Colombia were examined in this study. Nasal swabs, bronchial lavage and lung tissue samples were obtained from animals displaying symptoms compatible with SIV. Isolation of SIV was performed in 9-day embryonated chicken eggs or Madin-Darby Canine Kidney (MDCK) cells. Positive isolates, identified via the hemagglutination inhibition test, were further analyzed using PCR. Overall, 7 of the 11 farms were positive for SIV. Notably, sequencing of the gene encoding the hemagglutinin (HA) protein led to grouping of strains into circulating viruses identified during the human outbreak of 2009, classified as pandemic H1N1-2009. Serum samples from 198 gilts and multiparous sows between 2008 and 2009 were obtained to determine antibody presence of APP, Myh, PCV2 and PRRSV in both SIV-H1N1p-negative and -positive farms, but higher levels were recorded for SIV-H1N1p-positive farms. Odds ratio (OR) and P values revealed statistically significant differences (p<0.05) in PRDC presentation in gilts and multiparous sows of farms positive for SIV-H1N1p. Our findings indicate that positive farms have increased risk of PRDC presentation, in particular, PCV2, APP and Myh.

  19. Neuraminidase and hemagglutinin matching patterns of a highly pathogenic avian and two pandemic H1N1 influenza A viruses.

    Directory of Open Access Journals (Sweden)

    Yonghui Zhang

    Full Text Available BACKGROUND: Influenza A virus displays strong reassortment characteristics, which enable it to achieve adaptation in human infection. Surveying the reassortment and virulence of novel viruses is important in the prevention and control of an influenza pandemic. Meanwhile, studying the mechanism of reassortment may accelerate the development of anti-influenza strategies. METHODOLOGY/PRINCIPAL FINDINGS: The hemagglutinin (HA and neuraminidase (NA matching patterns of two pandemic H1N1 viruses (the 1918 and current 2009 strains and a highly pathogenic avian influenza A virus (H5N1 were studied using a pseudotyped particle (pp system. Our data showed that four of the six chimeric HA/NA combinations could produce infectious pps, and that some of the chimeric pps had greater infectivity than did their ancestors, raising the possibility of reassortment among these viruses. The NA of H5N1 (A/Anhui/1/2005 could hardly reassort with the HAs of the two H1N1 viruses. Many biological characteristics of HA and NA, including infectivity, hemagglutinating ability, and NA activity, are dependent on their matching pattern. CONCLUSIONS/SIGNIFICANCE: Our data suggest the existence of an interaction between HA and NA, and the HA NA matching pattern is critical for valid viral reassortment.

  20. Can breathing circuit filters help prevent the spread of influenza A (H1N1) virus from intubated patients?

    Science.gov (United States)

    Heuer, Jan F; Crozier, Thomas A; Howard, Glenn; Quintel, Michael

    2013-01-01

    Zielsetzung: Im März 2010 berichteten weltweit mehr als 213 Länder über laborchemisch bestätigte Influenza H1N1-Infektionen mit mindestens 16.813 Toten. In einigen Ländern wurden rund 10 bis 30% der hospitalisierten Patienten auf eine Intensivstation aufgenommen und bis zu 70% dieser Patienten benötigten eine mechanische Beatmung. Es stellt sich die Frage, ob Beatmungsfilter in der Lage sind Viruspartikel von einem infizierten Patienten daran zu hindern, das Beatmungsgerät sowie die Raumluft zu kontaminieren. Wir untersuchten Filter, die routinemäßig in unserer Abteilung benutzt werden, auf ihre Wirksamkeit und Effizienz hinsichtlich des Influenza Virus H1N1 (A/PR/8/34)). Methoden: Laboruntersuchungen von drei Filtern (PALL Ultipor(®) 25, Ultipor(®) 100 und Pall BB50T Beatmungsfilter, hergestellt von Pall Life Sciences) unter Verwendung eines monodispersen Aerosols von Influenza A (H1N1) Virus in einem Luftströmungsmodel mit Viruspartikeln quantifiziert als zytopathologische Effekte in kultivierten Kaninchen-Nierenzellen (MDCK). Ergebnisse: Die initiale Viruslast von 7.74±0.27 log10 wurde hinter den Filtern auf eine Viruslast von ≤2.43 log10 reduziert. Dieses Ergebnis entspricht einer Virusfiltration von ≥99.9995%.Schlussfolgerung: Die drei getesteten Filter verhinderten eine Ausbreitung des Virus, es deutet also daraufhin, dass die Verwendung dieser Filter das Risiko einer Virusübertragung von intubierten und beatmeten Patienten an das Beatmungsgerät und die Raumluft reduzieren kann.

  1. Carbohydrate determinants in ferret conjunctiva are affected by infection with influenza H1N1 virus

    DEFF Research Database (Denmark)

    Kirkeby, Svend; Martel, Cyril; Aasted, Bent

    2013-01-01

    Carbohydrates often accomplish as cell-surface receptors for microorganisms and influenza virus preferentially binds to sialic acid through the viral haemagglutinin. The virus may attach not only to the epithelium in the airways, but also to the surface ocular epithelium....

  2. Oseltamivir-resistant pandemic A(H1N1) 2009 influenza viruses detected through enhanced surveillance in the Netherlands, 2009-2010

    NARCIS (Netherlands)

    Meijer, Adam; Jonges, Marcel; Abbink, Floor; Ang, Wim; van Beek, Janko; Beersma, Matthias; Bloembergen, Peter; Boucher, Charles; Claas, Eric; Donker, Ge; van Gageldonk-Lafeber, Rianne; Isken, Leslie; Kroes, Aloys; Leenders, Sander; van der Lubben, Mariken; Mascini, Ellen; Niesters, Bert; Oosterheert, Jan Jelrik; Osterhaus, Albert; Riesmeijer, Rob; Riezebos-Brilman, Annelies; Schutten, Martin; Sebens, Fre; Stelma, Foekje; Swaan, Corien; Timen, Aura; van 't Veen, Annemarie; van der Vries, Erhard; Wierik, Margreet Te; Koopmans, Marion; de Jong, A

    2011-01-01

    Enhanced surveillance of infections due to the pandemic A(H1N1) influenza virus, which included monitoring for antiviral resistance, was carried out in the Netherlands from late April 2009 through late May 2010. More than 1100 instances of infection with the pandemic A(H1N1) influenza virus from 200

  3. Novel reassortant influenza viruses between pandemic (H1N1) 2009 and other influenza viruses pose a risk to public health.

    Science.gov (United States)

    Kong, Weili; Wang, Feibing; Dong, Bin; Ou, Changbo; Meng, Demei; Liu, Jinhua; Fan, Zhen-Chuan

    2015-12-01

    Influenza A virus (IAV) is characterized by eight single-stranded, negative sense RNA segments, which allows for gene reassortment among different IAV subtypes when they co-infect a single host cell simultaneously. Genetic reassortment is an important way to favor the evolution of influenza virus. Novel reassortant virus may pose a pandemic among humans. In history, three human pandemic influenza viruses were caused by genetic reassortment between avian, human and swine influenza viruses. Since 2009, pandemic (H1N1) 2009 (pdm/09 H1N1) influenza virus composed of two swine influenza virus genes highlighted the genetic reassortment again. Due to wide host species and high transmission of the pdm/09 H1N1 influenza virus, many different avian, human or swine influenza virus subtypes may reassert with it to generate novel reassortant viruses, which may result in a next pandemic among humans. So, it is necessary to understand the potential threat of current reassortant viruses between the pdm/09 H1N1 and other influenza viruses to public health. This study summarized the status of the reassortant viruses between the pdm/09 H1N1 and other influenza viruses of different species origins in natural and experimental conditions. The aim of this summarization is to facilitate us to further understand the potential threats of novel reassortant influenza viruses to public health and to make effective prevention and control strategies for these pathogens.

  4. Detection of swine-origin influenza A (H1N1) viruses using a paired surface plasma waves biosensor

    Science.gov (United States)

    Su, Li-Chen; Chang, Ying-Feng; Li, Ying-Chang; Hsieh, Jo-Ping; Lee, Cheng-Chung; Chou, Chien

    2010-08-01

    In order to enhance the sensitivity of conventional rapid test technique for the detection of swine-origin influenza A (H1N1) viruses (S-OIVs), we used a paired surface plasma waves biosensor (PSPWB) based on SPR in conjunction with an optical heterodyne technique. Experimentally, PSPWB showed a 125-fold improvement at least in the S-OIV detection as compared to conventional enzyme linked immunosorbent assay. Moreover, the detection limit of the PSPWB for the S-OIV detection was enhanced 250-fold in buffer at least in comparison with that of conventional rapid influenza diagnostic test.

  5. 人季节性H1N1流感病毒小鼠感染模型的建立%Establishment of a mouse infection model of human seasonal H1N1 influenza virus

    Institute of Scientific and Technical Information of China (English)

    郑倩倩; 毕振强; 赵丽; 谢克勤; 刘倜; 姚萍; 李忠; 温红玲; 宋艳艳; 王显军; 徐爱强

    2012-01-01

    目的 制备人季节性H1N1流感病毒的小鼠感染模型,为研究流感病毒致病性、研发抗病毒药物提供模型动物.方法 将人季节性H1N1流感病毒在鸡胚尿囊腔扩增后,滴鼻接种小鼠,4d后将小鼠处死,挑选感染体征严重者进行实时荧光PCR(FQ-PCR)检测肺中的流感病毒,将检测阳性的肺上清在鸡胚尿囊腔扩增,接种于下一代小鼠.比较各代小鼠对流感病毒的适应情况,直至小鼠出现明显的感染体征,取肺研磨制成匀浆,获得流感病毒鼠肺适应株并检测其半数致死量( LD50).将10 LD50的病毒液接种于小鼠,建立人季节性H1N1流感病毒的小鼠感染模型,观察模型小鼠的一般活动状态、体质量变化、肺部病变,HE染色观察肺部病理切片,计算肺指数,FQ-PCR检测病毒RNA.结果 人季节性流感病毒在小鼠体内传代4次后,鼠肺适应株制备完成,其经鼻的LD50为10-2.41/0.05 mL.人季节性流感病毒的小鼠感染模型,一般状态差,体质量明显减轻,肺指数增大,70%出现死亡.病理切片观察病变明显,FQ-PCR显示流感病毒阳性.结论 成功建立了人季节性H1N1流感病毒的小鼠感染模型.%Objective To establish a mouse infection model of human seasonal influenza virus ( HINl), and make preparations for the study on influenza viral pathogenicity and new antiviral drugs. Methods Mice were inoculated with influenza virus (H1 N1) by the nasal cavity. After 4 days, mice with serious infectious signs were killed. A pneumonic homogenate that was confirmed with influenza virus infection by real time fluorescence quantitative polymerase chain reaction (FQ-PCR) was injected into the chick embryo allantoic cavity. Allantoic fluid was inoculated in to the next generation of mice. When infected mice presented obvious infectious signs, the 50% lethal dose (LD50) was calculated. The virus of 10LD50 was inoculated into mice to establish the infection model. Then, general condition, weight

  6. Recipients of vaccine against the 1976 "swine flu" have enhanced neutralization responses to the 2009 novel H1N1 influenza virus.

    Science.gov (United States)

    McCullers, Jonathan A; Van De Velde, Lee-Ann; Allison, Kim J; Branum, Kristen C; Webby, Richard J; Flynn, Patricia M

    2010-06-01

    BACKGROUND. The world is facing a novel H1N1 influenza pandemic. A pandemic scare with a similar influenza virus in 1976 resulted in the vaccination of nearly 45 million persons. We hypothesized that prior receipt of the 1976 "swine flu" vaccine would enhance immune responses to the 2009 novel H1N1 influenza strain. METHODS. A prospective, volunteer sample of employees aged > or = 55 years at a children's cancer hospital in August 2009 was assessed for antibody responses to the 2009 pandemic H1N1 influenza virus and the 2008-2009 seasonal H1N1 influenza virus. RESULTS. Antibody responses by hemagglutination-inhibition assay were high against both the seasonal influenza virus (89.7% had a titer considered seroprotective) and pandemic H1N1 influenza virus (88.8% had a seroprotective titer). These antibodies were effective at neutralizing the seasonal H1N1 influenza virus in 68.1% of participants (titer > or = 40), but only 18.1% had detectable neutralizing titers against the pandemic H1N1 influenza virus. Of 116 participants, 46 (39.7%) received the 1976 "swine flu" vaccine. Receipt of this vaccine significantly enhanced neutralization responses; 8 (17.4%) of 46 vaccine recipients had titers > or = 160, compared with only 3 (4.3%) of 70 who did not receive the vaccine (P = .018 by chi(2) test). CONCLUSIONS. In this cohort, persons aged > or = 55 years had evidence of robust immunity to the 2008-2009 seasonal H1N1 influenza virus. These antibodies were cross-reactive but nonneutralizing against the 2009 pandemic H1N1 influenza strain. Receipt of a vaccine to a related virus significantly enhanced the neutralization capacity of these responses, suggesting homologous vaccination against the 2009 pandemic H1N1 influenza virus would have a similar effect.

  7. Point of care strategy for rapid diagnosis of novel A/H1N1 influenza virus.

    Directory of Open Access Journals (Sweden)

    Antoine Nougairede

    Full Text Available Within months of the emergence of the novel A/H1N1 pandemic influenza virus (nA/H1N1v, systematic screening for the surveillance of the pandemic was abandoned in France and in some other countries. At the end of June 2009, we implemented, for the public hospitals of Marseille, a Point Of Care (POC strategy for rapid diagnosis of the novel A/H1N1 influenza virus, in order to maintain local surveillance and to evaluate locally the kinetics of the pandemic.Two POC laboratories, located in strategic places, were organized to receive and test samples 24 h/24. POC strategy consisted of receiving and processing naso-pharyngeal specimens in preparation for the rapid influenza diagnostic test (RIDT and real-time RT-PCR assay (rtRT-PCR. This strategy had the theoretical capacity of processing up to 36 samples per 24 h. When the flow of samples was too high, the rtRT-PCR test was abandoned in the POC laboratories and transferred to the core virology laboratory. Confirmatory diagnosis was performed in the core virology laboratory twice a day using two distinct rtRT-PCR techniques that detect either influenza A virus or nA/N1N1v. Over a period of three months, 1974 samples were received in the POC laboratories, of which 111 were positive for nA/H1N1v. Specificity and sensitivity of RIDT were 100%, and 57.7% respectively. Positive results obtained using RIDT were transmitted to clinical practitioners in less than 2 hours. POC processed rtRT-PCR results were available within 7 hours, and rtRT-PCR confirmation within 24 hours.The POC strategy is of benefit, in all cases (with or without rtRT-PCR assay, because it provides continuous reception/processing of samples and reduction of the time to provide consolidated results to the clinical practitioners. We believe that implementation of the POC strategy for the largest number of suspect cases may improve the quality of patient care and our knowledge of the epidemiology of the pandemic.

  8. 58例甲型H1N1流感病毒性肺炎临床分析%Clinical analysis of 58 patients with influenza A (H1N1) virus pneumonia in our hospital

    Institute of Scientific and Technical Information of China (English)

    赵志海; 黄建安; 陈延斌; 张秀琴; 金均

    2011-01-01

    Objective To analyze the clinical features of influenza A (H1N1) virus pneumonia. Methods The clinical data of 58 patients with influenza A ( H1N1 )virus pneumonia in our hospital from 2009.10.31 to 2010. 1.15 were analyzed retrospectively, the severe cases,age,underlying diseases,respiratory symptoms,imaging datas,and prognosis. Results The Clinical features of 58 patients:high fever , coughing white mucus sputum ,inducing respiratory failure, X-ray chest radiography or chest CT shows patchy consolidation or ground-glass opacity in lung. 20 cases were severe pneumonia,4 cases of ARDS,4 cases with MODS, 3 cases were died. The treatment was mainly with Oseltamivir and corticosteroids,giving mechanical ventilation necessarily, assisting with nutritional support. Conclusion The key to improve the cure rate and reduce mortality is to make a diagnosis and treat the influenza A( H1N1 ) virus pneumonia as soon as possible.%目的 探讨H1N1流感病毒性肺炎的临床特点、治疗以及预后.方法 回顾性分析我院2009年10月31日-2010年1月15日58例H1N1流感病毒性肺炎的临床资料,并对重症病例、发病年龄、基础病、呼吸道症状、影像学资料、治疗及预后进行分析.结果 58例患者临床特点为:高热,咳白色粘液痰,可引起呼吸衰竭,全胸片或胸部CT示肺部斑片状致密影或磨玻璃影.治疗以奥司他韦,糖皮质激素为主,必要时予机械通气,辅以营养支持等,其中20例符合重症肺炎的诊断结果,4例并发ARDS,4例并发多脏器功能障碍,3例死亡.结论 及早诊断和治疗,是提高治愈率的关键.

  9. 1 case of H1N1 influenza virus infection combined with hemolytic anemia%甲型 H1 N1流感病毒感染合并溶血性贫血1例

    Institute of Scientific and Technical Information of China (English)

    李国强; 李国锋; 燕朋波; 魏路清

    2015-01-01

    报道1例甲型H1 N1流感病毒感染合并溶血性贫血病例,分析其临床表现、实验室检查及治疗经过特点,并进行文献复习。分析表明:对于H1 N1病毒感染可能合并溶血性贫血病例,临床给予血浆置换、机械通气和持续肾脏替代联合治疗( continuous renal replacement therapy, CRRT)可有效治愈。%A case of H1N1 influenza virus infection combined with hemolytic anemia were reported,and its clinical, laboratory characteristics and treatment of the case were reviewed, and related literature were reviewed as well.This case demonstrates that the ef-fective use of therapeutic plasma exchange, mechanical ventilation, and continuous renal replacement therapy ( CRRT) successfully made the patient recover from multiple organ failure.

  10. Molecular Characterization of Avian-like H1N1 Swine Influenza A Viruses Isolated in Eastern China, 2011

    Institute of Scientific and Technical Information of China (English)

    Xian Qi; Yuning Pan; Yuanfang Qin; Rongqiang Zu; Fengyang Tang; Minghao Zhou; Hua Wang; Yongchun Song

    2012-01-01

    Currently,three predominant subtypes of influenza virus are prevalent in pig populations worldwide:H1N1,H3N2,and H1N2.European avian-like H1N1 viruses,which were initially detected in European pig populations in 1979,have been circulating in pigs in eastern China since 2007.In this study,six influenza A viruses were isolated from 60 swine lung samples collected from January to April 2011 in eastern China.Based on whole genome sequencing,molecular characteristics of two isolates were determined.Phylogenetic analysis showed the eight genes of the two isolates were closely related to those of the avian-like H1N1 viruses circulating in pig populations,especially similar to those found in China.Four potential glycosylation sites were observed at positions 13,26,198,277 in the HA1 proteins of the two isolates.Due to the presence of a stop codon at codon 12,the isolates contained truncated PB1-F2 proteins.In this study,the isolates contained 591Q,627E and 701N in the polymerase subunit PB2,which had been shown to be determinants of virulence and host adaptation.The isolates also had a D rather than E at position 92 of the NS1,a marker of mammalian adaptation.Both isolates contained the GPKV motif at the PDZ ligand domain of the 3' end of the NS1,a characteristic marker of the European avian-like swine viruses since about 1999,which is distinct from those of avian,human and classical swine viruses.The M2 proteins of the isolates have the mutation (S31N),a characteristic marker of the European avian-like swine viruses since about 1987,which may confer resistance to amantadine and rimantadine antivirals.Our findings further emphasize the importance of surveillance on the genetic diversity of influenza A viruses in pigs,and raise more concerns about the occurrence of cross-species transmission events.

  11. Impact of Influenza A(H1N1)pdm09 Virus on Circulation Dynamics of Seasonal Influenza Strains in Kenya

    Science.gov (United States)

    Majanja, Janet; Njoroge, Rose N.; Achilla, Rachel; Wurapa, Eyako K.; Wadegu, Meshack; Mukunzi, Silvanos; Mwangi, Josephat; Njiri, James; Gachara, George; Bulimo, Wallace

    2013-01-01

    We describe virus variations from patients with influenza-like illness before and after the appearance of influenza A(H1N1)pdm09 in Kenya during January 2008–July 2011. A total of 11,592 nasopharyngeal swabs were collected from consenting patients. Seasonal influenza B, A/H1N1, A/H3N2, A/H5N1, and influenza A(H1N1)pdm09 viruses were detected by real-time reverse transcription–polymerase chain reaction. Of patients enrolled, 2073 (17.9%) had influenza. A total of 1,524 (73.4%) of 2,073 samples were positive for influenza A virus and 549 (26.6%) were positive for influenza B virus. Influenza B virus predominated in 2008 and seasonal A(H1N1) virus predominated in the first half of 2009. Influenza A(H1N1)pdm09 virus predominated in the second half of 2009. Influenza A/H3N2 virus predominated in 2010, and co-circulation of influenza A(H1N1)pdm09 virus and influenza B virus predominated the first half of 2011. The reduction and displacement of seasonal A(H1N1) virus was the most obvious effect of the arrival of influenza A(H1N1)pdm09 virus. The decision of the World Health Organization to replace seasonal A(H1N1) virus with the pandemic virus strain for the southern hemisphere vaccine was appropriate for Kenya. PMID:23458953

  12. Relapse of minimal change disease following infection with the 2009 pandemic influenza (H1N1) virus.

    Science.gov (United States)

    Kim, Seo Rin; Lee, Soo Bong; Kim, Il Young; Lee, Dong Won; Rhee, Harin; Seong, Eun Young; Song, Sang Heon; Kwak, Ihm Soo

    2012-04-01

    We report a case of relapse of minimal change disease following infection with the influenza A (H1N1) virus responsible for the 2009 pandemic. A 22-year-old man who had been diagnosed with minimal change disease presented with systemic edema. He had achieved complete remission with an oral steroid (prednisolone 1 mg/kg/day) by the 17th day of administration. On the 27th day of prednisolone administration, he presented with a new onset of generalized edema after several days of productive coughing. His urine showed proteinuria (4+) with a protein/creatinine ratio (PCR) of 2852.1 mg/g. His nasal swab sample was positive for the 2009 pandemic influenza (H1N1) virus by real-time reverse-transcriptase polymerase chain reaction (RT-PCR). He received oseltamivir (150 mg/day) for 5 days. A day after completing the oseltamivir therapy, his proteinuria returned to a normal range; urinalysis was negative for protein with PCR 79.2 mg/g. One month later, the patient remained normal with no proteinuria.

  13. Epidemiological and clinical characteristics of childhood pandemic 2009 H1N1 virus infection: an observational cohort study

    Directory of Open Access Journals (Sweden)

    Youn You-Sook

    2011-08-01

    Full Text Available Abstract Background There was a pandemic influenza around the world in 2009 including South Korea since last pandemic occurred four decades ago. We aimed to evaluate the epidemiological and clinical characteristics of this infection in childhood. Methods We evaluated the epidemiologic characteristics of all the subjects infected with the 2009 H1N1 influenza A virus (2,971 patients, ≤ 15 years of age, and the clinical and laboratory findings of the inpatients (217 patients, 80 had pneumonia between 1 September 2009 and 31 January 2010 in a single hospital throughout the epidemic. Results The age distribution of all the subjects was relatively even. Over 90% of cases occurred during a two-month period. Two hundred and five patients (94.5% received oseltamivir within 48 h of fever onset, and 97% of inpatients defervesced within 48 h of medication. The group with pneumonia included more males than females, and had higher leukocytes counts with lower lymphocyte differentials than the group without pneumonia. The white blood cell count and lymphocyte differential were associated with the severity of pneumonia. Corticosteroid treatment for severe pneumonia patients was highly effective in preventing disease progression. Conclusion Children of all ages affected with even rates of infection, but males were predominant in pneumonia patients. Pneumonia patients showed lymphopenia and its severity was associated with the severity of illness. Our results suggest that the mechanism of lung injury in 2009 H1N1 virus infection may be associated with the host immune response.

  14. In silico modification of oseltamivir as neuraminidase inhibitor of influenza A virus subtype H1N1

    Institute of Scientific and Technical Information of China (English)

    Usman Sumo Friend Tambunan; Rizky Archintya Rachmania; Arli Aditya Parikesit

    2015-01-01

    This research focused on the modification of the functional groups of oseltamivir as neuraminidase inhibitor against influenza A virus subtype H1N1.Interactions of three of the best ligands were evaluated in the hydrated state using molecular dynamics simulation at two different temperatures.The docking result showed that AD3BF2D ligand (N-[(1S,6R)-5-amino-5-{[(2R,3S,4S)-3,4-dihydroxy-4-(hydroxymethyl) tetrahydrofuran-2-yl]oxy}-4-formylcyclohex-3-en-l-yl]acetamide-3-(1-ethylpropoxy)-1-cyclohexene-1-carboxylate) had better binding energy values than standard oseltamivir.AD3BF2D had several interactions,including hydrogen bonds,with the residues in the catalytic site of neuraminidase as identified by molecular dynamics simulation.The results showed that AD3BF2D ligand can be used as a good candidate for neuraminidase inhibitor to cope with influenza A virus subtype H1N1.

  15. Immune and inflammatory response in pigs during acute influenza caused by H1N1 swine influenza virus.

    Science.gov (United States)

    Pomorska-Mól, Małgorzata; Markowska-Daniel, Iwona; Kwit, Krzysztof; Czyżewska, Ewelina; Dors, Arkadiusz; Rachubik, Jarosław; Pejsak, Zygmunt

    2014-10-01

    Swine influenza (SI) is an acute respiratory disease of pigs, caused by swine influenza virus (SIV). Little is known about the inflammatory response in the lung during acute SI and its correlation with clinical signs or lung pathology. Moreover, until now there has been a limited amount of data available on the relationship between the concentrations of pro- and anti-inflammatory cytokines in the lungs and the serum concentration of acute-phase proteins (APPs) in SIV-infected pigs. In the present study, the porcine inflammatory and immune responses during acute influenza caused by H1N1 SIV (SwH1N1) were studied. Nine pigs were infected intratracheally, and five served as controls. Antibodies against SIV were measured by haemagglutination inhibition assay, and the influenza-virus-specific T-cell response was measured using a proliferation assay. C-reactive protein (CRP), haptoglobin (Hp), serum amyloid A (SAA), and pig major acute-phase protein (Pig-MAP) the concentrations in serum and concentration of IL-1β, IL-6, IL-8, IL-10, TNF-α and IFN-γ in lung tissues were measured using commercial ELISAs.

  16. High-resolution computed tomography findings from adult patients with Influenza A (H1N1) virus-associated pneumonia

    Energy Technology Data Exchange (ETDEWEB)

    Marchiori, Edson [Fluminense Federal University, Rio de Janeiro (Brazil); Federal University of Rio de Janeiro, Rio de Janeiro (Brazil)], E-mail: edmarchiori@gmail.com; Zanetti, Glaucia [Federal University of Rio de Janeiro, Rio de Janeiro (Brazil)], E-mail: glauciazanetti@gmail.com; Hochhegger, Bruno [Federal University of Rio de Janeiro, Rio de Janeiro (Brazil)], E-mail: brunohochhegger@gmail.com; Rodrigues, Rosana Souza [Federal University of Rio de Janeiro, Rio de Janeiro (Brazil); D' OR Institute for Research and Education, Rio de Janeiro (Brazil)], E-mail: rosana.souzarodrigues@gmail.com; Fontes, Cristina Asvolinsque Pantaleao [Fluminense Federal University, Rio de Janeiro (Brazil)], E-mail: cristinasvolinsque@gmail.com; Nobre, Luiz Felipe [Santa Catarina Federal University, Florianopolis (Brazil)], E-mail: luizfelipenobresc@gmail.com; Dias Mancano, Alexandre [Anchieta Hospital, Taguatinga, DF (Brazil)], E-mail: alex.manzano1@gmail.com; Meirelles, Gustavo [Sao Paulo Federal University, Sao Paulo (Brazil)], E-mail: gmeirelles@gmail.com; Irion, Klaus Loureiro [Liverpool Heart and Chest Hospital NHS Trust, Liverpool (United Kingdom); Royal Liverpool and Broadgreen University Hospital NHS, Liverpool (United Kingdom)], E-mail: klaus.irion@btinternet.com

    2010-04-15

    Objective: The aim of this study was to assess the high-resolution computed tomography (HRCT) findings at presentation in patients diagnosed with Influenza A (H1N1) virus-associated pneumonia. Materials and methods: We reviewed the HRCT findings from 20 patients diagnosed with Influenza A (H1N1) and compared their HRCT scans with chest radiographs, obtained on the same day. The imaging studies were obtained 4-9 days after the onset of symptoms. The patients included 11 men and 9 women (ages 24-62 years; mean 42.7 years). All patients had a body temperature greater than 100.4 deg. F (>38 deg. C), tachypnea, and cough. Other common symptoms included diarrhea (60%) and sore throat (30%). The radiographs and HRCT scans were reviewed independently by two observers who reached a consensus decision. Results: The predominant HRCT findings consisted of bilateral ground-glass opacities (n = 12), bilateral areas of consolidation (n = 2), or a mixed bilateral pattern of ground-glass opacities and areas of consolidation (n = 6). The abnormalities were bilateral in all of the 20 patients, had a predominantly sub-pleural distribution in 13 patients, and had a random distribution in the remaining 7 patients. The predominant radiographic findings were consolidations. Normal radiographs were found in 4 out of the 20 patients. Conclusion: HRCT may reveal parenchymal abnormalities in patients with Influenza A (H1N1) infection who have normal findings on radiographs. The predominant HRCT findings were bilateral, peripheral, ground-glass opacities and/or bilateral areas of consolidation. The patients who presented consolidations had more severe clinical course.

  17. Influenza A Viruses Detected in Swine in Southern Germany after the H1N1 Pandemic in 2009.

    Science.gov (United States)

    Pippig, J; Ritzmann, M; Büttner, M; Neubauer-Juric, A

    2016-11-01

    Infections with influenza A viruses (IAV) are highly prevalent in swine populations, and stable cocirculation of at least three lineages has been well documented in European swine - till 2009. However, since the emergence of the human pandemic pdmH1N1 virus in 2009, which has been (re)introduced into individual swine herds worldwide, the situation has been changing. These variations in the respective IAV pools within pig populations are of major interest, and the zoonotic potential of putative emerging viruses needs to be evaluated. As data on recent IAV in swine from southern Germany were relatively sparse, the purpose of this study was to determine the major IAV subtypes actually present in this region. To this aim, from 2010 to 2013, 1417 nasal swabs or lung tissue samples from pigs with respiratory disease were screened for IAV genomes. Overall, in 130 holdings IAV genomes were detected by real-time RT-PCR targeting the matrix protein gene. For further analyses, several PCR protocols were adapted to quickly subtype between H1, pdmH1, H3, N1 and N2 sequences. Taken together, cocirculation of the three stable European lineages of IAV was confirmed for Bavaria. H1N1 sequences were identified in 59, whereas H1N2 genomes were only diagnosed in 14, and H3N2 in 9 of the holdings analysed. However, pdmH1 in combination with N1 was detected in 2010, 2012 and 2013 confirming a presence, albeit in low prevalence, likewise pdmH1N2 reassortant viruses. Interestingly, individual cases of coinfections with more than one subtype were diagnosed. Partial genome sequences were determined and phylogenetic analyses performed. Clearly other than in the human population classically circulating IAV have not been displaced by pdmH1N1 in Bavarian swine. However, some interesting viruses were detected. Further surveillance of these viruses in the Bavarian pig population will be of major importance, to monitor future developments. © 2016 Blackwell Verlag GmbH.

  18. Estimating the fitness advantage conferred by permissive neuraminidase mutations in recent oseltamivir-resistant A(H1N1)pdm09 influenza viruses.

    Science.gov (United States)

    Butler, Jeff; Hooper, Kathryn A; Petrie, Stephen; Lee, Raphael; Maurer-Stroh, Sebastian; Reh, Lucia; Guarnaccia, Teagan; Baas, Chantal; Xue, Lumin; Vitesnik, Sophie; Leang, Sook-Kwan; McVernon, Jodie; Kelso, Anne; Barr, Ian G; McCaw, James M; Bloom, Jesse D; Hurt, Aeron C

    2014-04-01

    Oseltamivir is relied upon worldwide as the drug of choice for the treatment of human influenza infection. Surveillance for oseltamivir resistance is routinely performed to ensure the ongoing efficacy of oseltamivir against circulating viruses. Since the emergence of the pandemic 2009 A(H1N1) influenza virus (A(H1N1)pdm09), the proportion of A(H1N1)pdm09 viruses that are oseltamivir resistant (OR) has generally been low. However, a cluster of OR A(H1N1)pdm09 viruses, encoding the neuraminidase (NA) H275Y oseltamivir resistance mutation, was detected in Australia in 2011 amongst community patients that had not been treated with oseltamivir. Here we combine a competitive mixtures ferret model of influenza infection with a mathematical model to assess the fitness, both within and between hosts, of recent OR A(H1N1)pdm09 viruses. In conjunction with data from in vitro analyses of NA expression and activity we demonstrate that contemporary A(H1N1)pdm09 viruses are now more capable of acquiring H275Y without compromising their fitness, than earlier A(H1N1)pdm09 viruses circulating in 2009. Furthermore, using reverse engineered viruses we demonstrate that a pair of permissive secondary NA mutations, V241I and N369K, confers robust fitness on recent H275Y A(H1N1)pdm09 viruses, which correlated with enhanced surface expression and enzymatic activity of the A(H1N1)pdm09 NA protein. These permissive mutations first emerged in 2010 and are now present in almost all circulating A(H1N1)pdm09 viruses. Our findings suggest that recent A(H1N1)pdm09 viruses are now more permissive to the acquisition of H275Y than earlier A(H1N1)pdm09 viruses, increasing the risk that OR A(H1N1)pdm09 will emerge and spread worldwide.

  19. Estimating the fitness advantage conferred by permissive neuraminidase mutations in recent oseltamivir-resistant A(H1N1pdm09 influenza viruses.

    Directory of Open Access Journals (Sweden)

    Jeff Butler

    2014-04-01

    Full Text Available Oseltamivir is relied upon worldwide as the drug of choice for the treatment of human influenza infection. Surveillance for oseltamivir resistance is routinely performed to ensure the ongoing efficacy of oseltamivir against circulating viruses. Since the emergence of the pandemic 2009 A(H1N1 influenza virus (A(H1N1pdm09, the proportion of A(H1N1pdm09 viruses that are oseltamivir resistant (OR has generally been low. However, a cluster of OR A(H1N1pdm09 viruses, encoding the neuraminidase (NA H275Y oseltamivir resistance mutation, was detected in Australia in 2011 amongst community patients that had not been treated with oseltamivir. Here we combine a competitive mixtures ferret model of influenza infection with a mathematical model to assess the fitness, both within and between hosts, of recent OR A(H1N1pdm09 viruses. In conjunction with data from in vitro analyses of NA expression and activity we demonstrate that contemporary A(H1N1pdm09 viruses are now more capable of acquiring H275Y without compromising their fitness, than earlier A(H1N1pdm09 viruses circulating in 2009. Furthermore, using reverse engineered viruses we demonstrate that a pair of permissive secondary NA mutations, V241I and N369K, confers robust fitness on recent H275Y A(H1N1pdm09 viruses, which correlated with enhanced surface expression and enzymatic activity of the A(H1N1pdm09 NA protein. These permissive mutations first emerged in 2010 and are now present in almost all circulating A(H1N1pdm09 viruses. Our findings suggest that recent A(H1N1pdm09 viruses are now more permissive to the acquisition of H275Y than earlier A(H1N1pdm09 viruses, increasing the risk that OR A(H1N1pdm09 will emerge and spread worldwide.

  20. Estimating the Fitness Advantage Conferred by Permissive Neuraminidase Mutations in Recent Oseltamivir-Resistant A(H1N1)pdm09 Influenza Viruses

    Science.gov (United States)

    Butler, Jeff; Hooper, Kathryn A.; Petrie, Stephen; Lee, Raphael; Maurer-Stroh, Sebastian; Reh, Lucia; Guarnaccia, Teagan; Baas, Chantal; Xue, Lumin; Vitesnik, Sophie; Leang, Sook-Kwan; McVernon, Jodie; Kelso, Anne; Barr, Ian G.; McCaw, James M.; Bloom, Jesse D.; Hurt, Aeron C.

    2014-01-01

    Oseltamivir is relied upon worldwide as the drug of choice for the treatment of human influenza infection. Surveillance for oseltamivir resistance is routinely performed to ensure the ongoing efficacy of oseltamivir against circulating viruses. Since the emergence of the pandemic 2009 A(H1N1) influenza virus (A(H1N1)pdm09), the proportion of A(H1N1)pdm09 viruses that are oseltamivir resistant (OR) has generally been low. However, a cluster of OR A(H1N1)pdm09 viruses, encoding the neuraminidase (NA) H275Y oseltamivir resistance mutation, was detected in Australia in 2011 amongst community patients that had not been treated with oseltamivir. Here we combine a competitive mixtures ferret model of influenza infection with a mathematical model to assess the fitness, both within and between hosts, of recent OR A(H1N1)pdm09 viruses. In conjunction with data from in vitro analyses of NA expression and activity we demonstrate that contemporary A(H1N1)pdm09 viruses are now more capable of acquiring H275Y without compromising their fitness, than earlier A(H1N1)pdm09 viruses circulating in 2009. Furthermore, using reverse engineered viruses we demonstrate that a pair of permissive secondary NA mutations, V241I and N369K, confers robust fitness on recent H275Y A(H1N1)pdm09 viruses, which correlated with enhanced surface expression and enzymatic activity of the A(H1N1)pdm09 NA protein. These permissive mutations first emerged in 2010 and are now present in almost all circulating A(H1N1)pdm09 viruses. Our findings suggest that recent A(H1N1)pdm09 viruses are now more permissive to the acquisition of H275Y than earlier A(H1N1)pdm09 viruses, increasing the risk that OR A(H1N1)pdm09 will emerge and spread worldwide. PMID:24699865

  1. Efficacy of a pandemic (H1N1) 2009 virus vaccine in pigs against the pandemic influenza virus is superior to commercially available swine influenza vaccines.

    Science.gov (United States)

    Loeffen, W L A; Stockhofe, N; Weesendorp, E; van Zoelen-Bos, D; Heutink, R; Quak, S; Goovaerts, D; Heldens, J G M; Maas, R; Moormann, R J; Koch, G

    2011-09-28

    In April 2009 a new influenza A/H1N1 strain, currently named "pandemic (H1N1) influenza 2009" (H1N1v), started the first official pandemic in humans since 1968. Several incursions of this virus in pig herds have also been reported from all over the world. Vaccination of pigs may be an option to reduce exposure of human contacts with infected pigs, thereby preventing cross-species transfer, but also to protect pigs themselves, should this virus cause damage in the pig population. Three swine influenza vaccines, two of them commercially available and one experimental, were therefore tested and compared for their efficacy against an H1N1v challenge. One of the commercial vaccines is based on an American classical H1N1 influenza strain, the other is based on a European avian H1N1 influenza strain. The experimental vaccine is based on reassortant virus NYMC X179A (containing the hemagglutinin (HA) and neuraminidase (NA) genes of A/California/7/2009 (H1N1v) and the internal genes of A/Puerto Rico/8/34 (H1N1)). Excretion of infectious virus was reduced by 0.5-3 log(10) by the commercial vaccines, depending on vaccine and sample type. Both vaccines were able to reduce virus replication especially in the lower respiratory tract, with less pathological lesions in vaccinated and subsequently challenged pigs than in unvaccinated controls. In pigs vaccinated with the experimental vaccine, excretion levels of infectious virus in nasal and oropharyngeal swabs, were at or below 1 log(10)TCID(50) per swab and lasted for only 1 or 2 days. An inactivated vaccine containing the HA and NA of an H1N1v is able to protect pigs from an infection with H1N1v, whereas swine influenza vaccines that are currently available are of limited efficaciousness. Whether vaccination of pigs against H1N1v will become opportune remains to be seen and will depend on future evolution of this strain in the pig population. Close monitoring of the pig population, focussing on presence and evolution of

  2. Detection of extensive cross-neutralization between pandemic and seasonal A/H1N1 Influenza Viruses using a pseudotype neutralization assay.

    Directory of Open Access Journals (Sweden)

    Béatrice Labrosse

    Full Text Available BACKGROUND: Cross-immunity between seasonal and pandemic A/H1N1 influenza viruses remains uncertain. In particular, the extent that previous infection or vaccination by seasonal A/H1N1 viruses can elicit protective immunity against pandemic A/H1N1 is unclear. METHODOLOGY/PRINCIPAL FINDINGS: Neutralizing titers against seasonal A/H1N1 (A/Brisbane/59/2007 and against pandemic A/H1N1 (A/California/04/2009 were measured using an HIV-1-based pseudovirus neutralization assay. Using this highly sensitive assay, we found that a large fraction of subjects who had never been exposed to pandemic A/H1N1 express high levels of pandemic A/H1N1 neutralizing titers. A significant correlation was seen between neutralization of pandemic A/H1N1 and neutralization of a standard seasonal A/H1N1 strain. Significantly higher pandemic A/H1N1 neutralizing titers were measured in subjects who had received vaccination against seasonal influenza in 2008-2009. Higher pandemic neutralizing titers were also measured in subjects over 60 years of age. CONCLUSIONS/SIGNIFICANCE: Our findings reveal that the extent of protective cross-immunity between seasonal and pandemic A/H1N1 influenza viruses may be more important than previously estimated. This cross-immunity could provide a possible explanation of the relatively mild profile of the recent influenza pandemic.

  3. Origin and future distribution of the new A (H1N1) influenza virus emerging in North America in 2009

    Institute of Scientific and Technical Information of China (English)

    CHEN JiMing; SUN YingXue; LIU Shuo; JIANG WenMing; CHEN Jie; HOU GuangYu; LI JinPing

    2009-01-01

    The origin of the new A (H1N1) influenza virus recently emerging in North America is a hot controversial topic of significance in disease control and risk assessment.Some experts claimed that it was an unusually mongrelized mix of human,avian and swine influenza viruses,while some others concluded that it was totally a simple re-assortment hybrid of two lineages of swine influenza viruses.Here the phylogenetic diversity of the viral PB1,PA and PB2 gene sequences using online web servers,and the results suggest that all the 8 genetic segments of the new virus were possibly from two lineages of swine influenza viruses,and one of the lineage was a mongrelized mix of human,avian and swine influenza viruses emerging in the world approximately 10 years ago.Considering the recent epidemiological trends of the new virus,we believe it will spread more widely in the world and persist long in human populations.It also could spread among swine populations.The future wide spreading of the new virus may coincide the disappearance of a subtype of previous human influenza A virus.

  4. Probable transmisión vertical del virus de la influenza A (H1N1): a propósito de un caso Probable vertical transmission of the influenza virus A (H1N1): apropos of a case

    OpenAIRE

    Rubén D. Vásquez; Víctor M. Chávez; Iris E. Gamio; Richard I. Muñoz; Marcos F. Polar; Raúl Montalvo; Eduardo Ticona

    2010-01-01

    Se reporta el caso de un recién nacido varón, producto de embarazo de 36 semanas, con diagnóstico de neumonía congénita y examen confirmatorio de infección por el virus de la influenza A (H1N1), sin ningún otro tipo de contacto sospechoso. La madre ingresó al hospital con insuficiencia respiratoria y antecedente de proceso gripal de cinco días de evolución, durante los primeros días de la pandemia en el Perú. Por la evolución grave del proceso respiratorio, se le administró ventilación mecáni...

  5. Dynamics of a New Strain of the H1N1 Influenza A Virus Incorporating the Effects of Repetitive Contacts

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    Puntani Pongsumpun

    2014-01-01

    Full Text Available The respiratory disease caused by the Influenza A Virus is occurring worldwide. The transmission for new strain of the H1N1 Influenza A virus is studied by formulating a SEIQR (susceptible, exposed, infected, quarantine, and recovered model to describe its spread. In the present model, we have assumed that a fraction of the infected population will die from the disease. This changes the mathematical equations governing the transmission. The effect of repetitive contact is also included in the model. Analysis of the model by using standard dynamical modeling method is given. Conditions for the stability of equilibrium state are given. Numerical solutions are presented for different values of parameters. It is found that increasing the amount of repetitive contacts leads to a decrease in the peak numbers of exposed and infectious humans. A stability analysis shows that the solutions are robust.

  6. Comparing Deaths from Influenza H1N1 and Seasonal Influenza A: Main Sociodemographic and Clinical Differences between the Most Prevalent 2009 Viruses

    Science.gov (United States)

    Gutierrez, Juan Pablo

    2012-01-01

    Background. During the 2009 spring epidemic outbreak in Mexico, an important research and policy question faced was related to the differences in clinical profile and population characteristics of those affected by the new H1N1 virus compared with the seasonal virus. Methods and Findings. Data from clinical files from all influenza A deaths in Mexico between April 10 and July 13, 2009 were analyzed to describe differences in clinical and socioeconomic profile between H1N1 and non-H1N1 cases. A total of 324 influenza A mortality cases were studied of which 239 presented rt-PCR confirmation for H1N1 virus and 85 for seasonal influenza A. From the differences of means and multivariate logistic regression, it was found that H1N1 deaths occurred in younger and less educated people, and among those who engage in activities where there is increased contact with other unknown persons (OR 4.52, 95% CI 1.56–13.14). Clinical symptoms were similar except for dyspnea, headache, and chest pain that were less frequently found among H1N1 cases. Conclusions. Findings suggest that age, education, and occupation are factors that may be useful to identify risk for H1N1 among influenza cases, and also that patients with early dyspnea, headache, and chest pain are more likely to be non-H1N1 cases. PMID:23346393

  7. Safety of Vaccine for A/H1N1 Influenza Split Virus%甲型H1N1流行性感冒病毒裂解疫苗的安全性监测

    Institute of Scientific and Technical Information of China (English)

    李建坡; 李瑞芳; 李琦; 张连山; 张富斌; 尹增慧

    2013-01-01

    Objective To evaluate the safety of vaccine for A/H1N1 influenza split virus.Methods At surveillance spots,AEFI cases of A/H1N1 vaccine and seasonal influenza vaccine were collected through National Adverse Events Following Immunization (AEFI) Surveillance System.The data were analyzed with descriptive methodology.Results The incidence of reported AEFI cases of influenza A/H1N1 vaccination was 14.64/105,mainly general reactions with fever below 38.5℃.No serious adverse reactions and implementation of error accidents occurred.The incidence of AEFI cases of influenza A/H1N1 vaccination was 752.63/105,which were all general reactions and mostly fever.The incidence of AEFI cases of seasonal influenza vaccination was 203.14/105,which were also all general reactions of fever.Conclusion The incidence of influenza A/H1N1 vaccination was higher than that of seasonal influenza vaccination,mild fever as the dominating reaction.The influenza A/H1N1 vaccine was safe.%目的 评价甲型H1N1流行性感冒裂解疫苗(甲流疫苗)的安全性.方法 设立主动监测点,通过全国疑似预防接种异常反应(Adverse Events Following Immunization,AEFI)信息管理系统,收集邯郸市2009-10/2010-05接种甲流疫苗和主动监测点接种季节性流感疫苗后的AEFI个案信息,采用描述性方法对相关指标进行流行病学分析.结果 邯郸市常规报告接种甲流疫苗717 288人,发生AEFI 105例,AEFI发生率14.64/10万,以一般反应为主,占88.57%,症状主要为38.5℃以下的低热,无严重不良反应和接种事故发生.主动监测点接种甲流疫苗1 993人,发生AEFI 15例,AEFI发生率752.63/10万,全部为一般反应,以发热为主.主动监测点接种季节性流感疫苗1 969人,发生AEFI 4例,AEFI发生率203.14/10万,全部为一般反应,均为发热.结论 邯郸市监测点甲流疫苗接种后AEFI发生率高于季节性流感疫苗,反应类型以一般反应为主,且多为低热.甲流疫苗是安全的.

  8. Estimating the Disease Burden of Pandemic (H1N1) 2009 Virus Infection in Hunter New England, Northern New South Wales, Australia, 2009

    Science.gov (United States)

    Dawood, Fatimah S.; Hope, Kirsty G.; Durrheim, David N.; Givney, Rodney; Fry, Alicia M.; Dalton, Craig B.

    2010-01-01

    Introduction On May 26, 2009, the first confirmed case of Pandemic (H1N1) 2009 virus (pH1N1) infection in Hunter New England (HNE), New South Wales (NSW), Australia (population 866,000) was identified. We used local surveillance data to estimate pH1N1-associated disease burden during the first wave of pH1N1 circulation in HNE. Methods Surveillance was established during June 1-August 30, 2009, for: 1) laboratory detection of pH1N1 at HNE and NSW laboratories, 2) pH1N1 community influenza-like illness (ILI) using an internet survey of HNE residents, and 3) pH1N1-associated hospitalizations and deaths using respiratory illness International Classification of Diseases 10 codes at 35 HNE hospitals and mandatory reporting of confirmed pH1N1-associated hospitalizations and deaths to the public health service. The proportion of pH1N1 positive specimens was applied to estimates of ILI, hospitalizations, and deaths to estimate disease burden. Results Of 34,177 specimens tested at NSW laboratories, 4,094 (12%) were pH1N1 positive. Of 1,881 specimens from patients evaluated in emergency departments and/or hospitalized, 524 (26%) were pH1N1 positive. The estimated number of persons with pH1N1-associated ILI in the HNE region was 53,383 (range 37,828–70,597) suggesting a 6.2% attack rate (range 4.4–8.2%). An estimated 509 pH1N1-associated hospitalizations (range 388–630) occurred (reported: 184), and up to 10 pH1N1-associated deaths (range 8–13) occurred (reported: 5). The estimated case hospitalization ratio was 1% and case fatality ratio was 0.02%. Discussion The first wave of pH1N1 activity in HNE resulted in symptomatic infection in a small proportion of the population, and the number of HNE pH1N1-associated hospitalizations and deaths is likely higher than officially reported. PMID:20360868

  9. Hospitalized patients with novel influenza A (H1N1) virus infection: Shanghai, June-July 2009

    Institute of Scientific and Technical Information of China (English)

    XIAO Hong; LU Shui-hua; OU Qiang; CHEN Ying-ying; HUANG Shao-ping

    2010-01-01

    Background From late May 2009, sporadic imported cases of novel influenza A (H1N1) were continuously confirmed in Shanghai, but there were few reports on its clinical presentation in China. The aim of the study was to investigate the demographic and clinical features of the laboratory-confirmed cases and the treatment with oseltamivir.Method We performed a retrospective study in the Shanghai Public Health Clinical Center (SHAPHC), reviewing the medical records of the laboratory-confirmed patients derived from June 10 to July 20, 2009. Results Atotal of 156 cases were enrolled, of whom 152 had a history of recent travel. The mean age was 22.6 years and 89 cases (57.1%) were males. The most common symptoms were fever, cough, and sore throat, with children more likely to run a temperature above 38.5℃ than adults. The mean leucocyte count was 5.4×10~9/L, the mean neutrophil count 3.2×10~9/L and the mean lymphocyte count 1.4×10~9/L. Other findings included a normal range or elevated level of C-reactive protein (CRP) and glutamic-pyruvic transaminase and a normal or decreased level of prealbumin; the levels of prealbumin and CRP were significantly lower in the children than in the adults. Fifty-two patients had abnormal chest CT results, with small unilateral or bilateral pulmonary infiltrates, axillary and mediastinal lymphadenopathy and local pleural thickening, while no cases showed symptoms of hypoxia. All the patients received oseltamivir and recovered without complications, but the duration of fever and virus shedding were significantly longer in the children than in the adults. Conclusions Travel-related circulation may be an important reason for the H1N1 epidemic in the non-epidemic areas, and the virus caused mild respiratory symptoms. The infection in children was more severe in terms of prealbumin levels, temperature, the duration of fever and virus shedding. Oseltamivir was effective for H1N1, but more effective in the adults than in the children.

  10. Intensive cytokine induction in pandemic H1N1 influenza virus infection accompanied by robust production of IL-10 and IL-6.

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    Xuelian Yu

    Full Text Available BACKGROUND: The innate immune system is the first line of defense against viruses by inducing expression of cytokines and chemokines. Many pandemic influenza H1N1 virus [P(H1N1] infected severe cases occur in young adults under 18 years old who were rarely seriously affected by seasonal influenza. Results regarding host cytokine profiles of P(H1N1 are ambivalent. In the present study we investigated host cytokine profiles in P(H1N1 patients and identified cytokines related to disease severity. METHODS AND PRINCIPAL FINDINGS: We retrieved 77, 59, 26 and 26 sera samples from P(H1N1 and non-flu influenza like illness (non-ILIs cases with mild symptoms (mild patients, P(H1N1 vaccinees and healthy individuals, respectively. Nine and 16 sera were from hospitalized P(H1N1 and non-ILIs patients with severe symptoms (severe patients. Cytokines of IL-1, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IFN-γ and TNF-α were assayed by cytokine bead array, IL-17 and IL-23 measured with ELISA. Mild P(H1N1 patients produced significantly elevated IL-2, IL-12, IFN-γ, IL-6, TNF-α, IL-5, IL-10, IL-17 and IL-23 versus to healthy controls. While an overwhelming IL-6 and IL-10 production were observed in severe P(H1N1 patients. Higher IL-10 secretion in P(H1N1 vaccinees confirmed our observation that highly increased level of sera IL-6 and IL-10 in P(H1N1 patients may lead to disease progression. CONCLUSION AND SIGNIFICANCE: A comprehensive innate immune response was activated at the early stage of P(H1N1 infection with a combine Th1/Th2/Th3 cytokines production. As disease progression, a systemic production of IL-6 and IL-10 were observed in severe P(H1N1 patients. Further analysis found a strong correlation between IL-6 and IL-10 production in the severe P(H1N1 patients. IL-6 may be served as a mediator to induce IL-10 production. Highly elevated level of sera IL-6 and IL-10 in P(H1N1 patients may lead to disease progression, but the underlying mechanism awaits

  11. A case of benign acute childhood myositis associated with influenza A (H1N1) virus infection.

    Science.gov (United States)

    Koliou, M; Hadjiloizou, S; Ourani, S; Demosthenous, A; Hadjidemetriou, A

    2010-02-01

    Benign acute childhood myositis (BACM) is a rare transient condition usually occurring at the early convalescent phase of a viral upper respiratory tract illness, normally influenza A, and, more frequently, influenza B infection. It is characterized by acute-onset difficulty in walking as a result of severe bilateral calf pain and by elevated muscle enzymes including creatinine kinase. It is self-limiting because there is rapid full recovery usually within 1 week. We describe the first case of BACM in association with the new pandemic influenza A (H1N1) virus infection in an 11-year-old boy from Cyprus. The child had the typical clinical and laboratory characteristics of this clinical syndrome. Prompt diagnosis of this clinical entity is essential to prevent unnecessary investigations and therapeutic interventions and to reassure the patient and parents of the excellent prognosis.

  12. TGF-β Blood Levels Distinguish Between Influenza A (H1N1)pdm09 Virus Sepsis and Sepsis due to Other Forms of Community-Acquired Pneumonia.

    Science.gov (United States)

    Rendón-Ramirez, Erick J; Ortiz-Stern, Alejandro; Martinez-Mejia, Corazon; Salinas-Carmona, Mario C; Rendon, Adrian; Mata-Tijerina, Viviana L; Rosas-Taraco, Adrian G

    2015-06-01

    There is a strong interest in finding adequate biomarkers to aid in the diagnosis and prognosis of influenza A (H1N1)pdm09 virus infection. In this study, serum levels of inflammatory cytokines and laboratory markers were evaluated to assess their usefulness as biomarkers of influenza A (H1N1)pdm09 and their association with fatal cases. Serum samples of consecutive patients with a clinical presentation suggestive of influenza A (H1N1)pdm09 and progression to sepsis were evaluated. Serum inflammatory cytokines and routine laboratory tests were performed and correlated with positivity for influenza A (H1N1)pdm09 influenza by real time reverse transcription polymerase chain reaction and the results of three clinical severity scores (Sequential Organ Failure Assessment [SOFA], CURB-65, and Acute Physiology and Chronic Health Evaluation II [APACHE II]). High SOFA scores and some of its individual components, but not CURB-65 or APACHE II scores, correlate with fatal cases regardless of etiology. Total and unconjugated bilirubin, Ca(++), Cl(-), prothrombin times, and partial thromboplastin times discriminate influenza A (H1N1)pdm09 from other causes of community-acquired pneumonia. High levels of IL-8, IL-10, and IL-17 were increased in influenza A (H1N1)pdm09 patients when compared with controls (pH1N1)pdm09 patients and non-(H1N1)pdm09 patients when compared with controls (pH1N1)pdm09 patients, and patients with other causes of community-acquired pneumonia. TGF-β levels were negatively correlated with SOFA on admission in influenza A (H1N1)pdm09 patients. TGF-β levels are a useful tool for differentiating influenza A (H1N1)pdm09 from other causes of pneumonia progressing to sepsis.

  13. CD206+ Cell Number Differentiates Influenza A (H1N1pdm09 from Seasonal Influenza A Virus in Fatal Cases

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    Heidi G. Rodriguez-Ramirez

    2014-01-01

    Full Text Available In 2009, a new influenza A (H1N1 virus affected many persons around the world. There is an urgent need for finding biomarkers to distinguish between influenza A (H1N1pdm09 and seasonal influenza virus. We investigated these possible biomarkers in the lung of fatal cases of confirmed influenza A (H1N1pdm09. Cytokines (inflammatory and anti-inflammatory and cellular markers (macrophages and lymphocytes subpopulation markers were analyzed in lung tissue from both influenza A (H1N1pdm09 and seasonal influenza virus. High levels of IL-17, IFN-γ, and TNF-α positive cells were identical in lung tissue from the influenza A (H1N1pdm09 and seasonal cases when compared with healthy lung tissue (P<0.05. Increased IL-4+ cells, and CD4+ and CD14+ cells were also found in high levels in both influenza A (H1N1pdm09 and seasonal influenza virus (P<0.05. Low levels of CD206+ cells (marker of alternatively activated macrophages marker in lung were found in influenza A (H1N1pdm09 when compared with seasonal influenza virus (P<0.05, and the ratio of CD206/CD14+ cells was 2.5-fold higher in seasonal and noninfluenza group compared with influenza A (H1N1pdm09 (P<0.05. In conclusion, CD206+ cells differentiate between influenza A (H1N1pdm09 and seasonal influenza virus in lung tissue of fatal cases.

  14. CD206+ Cell Number Differentiates Influenza A (H1N1)pdm09 from Seasonal Influenza A Virus in Fatal Cases

    Science.gov (United States)

    Rodriguez-Ramirez, Heidi G.; Salinas-Carmona, Mario C.; Barboza-Quintana, Oralia; Melo-de la Garza, Americo; Ceceñas-Falcon, Luis Angel; Rangel-Martinez, Lilia M.; Rosas-Taraco, Adrian G.

    2014-01-01

    In 2009, a new influenza A (H1N1) virus affected many persons around the world. There is an urgent need for finding biomarkers to distinguish between influenza A (H1N1)pdm09 and seasonal influenza virus. We investigated these possible biomarkers in the lung of fatal cases of confirmed influenza A (H1N1)pdm09. Cytokines (inflammatory and anti-inflammatory) and cellular markers (macrophages and lymphocytes subpopulation markers) were analyzed in lung tissue from both influenza A (H1N1)pdm09 and seasonal influenza virus. High levels of IL-17, IFN-γ, and TNF-α positive cells were identical in lung tissue from the influenza A (H1N1)pdm09 and seasonal cases when compared with healthy lung tissue (P < 0.05). Increased IL-4+ cells, and CD4+ and CD14+ cells were also found in high levels in both influenza A (H1N1)pdm09 and seasonal influenza virus (P < 0.05). Low levels of CD206+ cells (marker of alternatively activated macrophages marker in lung) were found in influenza A (H1N1)pdm09 when compared with seasonal influenza virus (P < 0.05), and the ratio of CD206/CD14+ cells was 2.5-fold higher in seasonal and noninfluenza group compared with influenza A (H1N1)pdm09 (P < 0.05). In conclusion, CD206+ cells differentiate between influenza A (H1N1)pdm09 and seasonal influenza virus in lung tissue of fatal cases. PMID:25614715

  15. Comparative pathogenesis of an avian H5N2 and a swine H1N1 influenza virus in pigs.

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    Annebel De Vleeschauwer

    Full Text Available Pigs are considered intermediate hosts for the transmission of avian influenza viruses (AIVs to humans but the basic organ pathogenesis of AIVs in pigs has been barely studied. We have used 42 four-week-old influenza naive pigs and two different inoculation routes (intranasal and intratracheal to compare the pathogenesis of a low pathogenic (LP H5N2 AIV with that of an H1N1 swine influenza virus. The respiratory tract and selected extra-respiratory tissues were examined for virus replication by titration, immunofluorescence and RT-PCR throughout the course of infection. Both viruses caused a productive infection of the entire respiratory tract and epithelial cells in the lungs were the major target. Compared to the swine virus, the AIV produced lower virus titers and fewer antigen positive cells at all levels of the respiratory tract. The respiratory part of the nasal mucosa in particular showed only rare AIV positive cells and this was associated with reduced nasal shedding of the avian compared to the swine virus. The titers and distribution of the AIV varied extremely between individual pigs and were strongly affected by the route of inoculation. Gross lung lesions and clinical signs were milder with the avian than with the swine virus, corresponding with lower viral loads in the lungs. The brainstem was the single extra-respiratory tissue found positive for virus and viral RNA with both viruses. Our data do not reject the theory of the pig as an intermediate host for AIVs, but they suggest that AIVs need to undergo genetic changes to establish full replication potential in pigs. From a biomedical perspective, experimental LP H5 AIV infection of pigs may be useful to examine heterologous protection provided by H5 vaccines or other immunization strategies, as well as for further studies on the molecular pathogenesis and neurotropism of AIVs in mammals.

  16. Pneumonia in novel swine-origin influenza A (H1N1) virus infection: High-resolution CT findings

    Energy Technology Data Exchange (ETDEWEB)

    Li Ping, E-mail: pinglee_2000@yahoo.com [Department of Radiology, The Second Affiliated Hospital of Harbin Medical University, 246 Xue Fu Road, Harbin 150086 (China); Su Dongju, E-mail: hyd_sdj@yahoo.com.cn [Department of Respiratory, The Second Affiliated Hospital of Harbin Medical University, 246 Xue Fu Road, Harbin 150086 (China); Zhang Jifeng, E-mail: zjf2005520@163.com [Department of Radiology, The Second Affiliated Hospital of Harbin Medical University, 246 Xue Fu Road, Harbin 150086 (China); Xia Xudong, E-mail: xiaxd888@163.com [Department of Radiology, The Second Affiliated Hospital of Harbin Medical University, 246 Xue Fu Road, Harbin 150086 (China); Sui Hong, E-mail: suisuihong@126.com [Department of Statistics, Harbin Medical University, 240 Xue Fu Road, Harbin 150086 (China); Zhao Donghui, E-mail: yhwoooooo@yahoo.com.cn [Centers for Disease Control and Prevention of Heilongjiang, 187 Xiang An Street, Harbin 150036 (China)

    2011-11-15

    Objective: The purpose of our study was to review the initial high-resolution CT (HRCT) findings in pneumonia patients with presumed/laboratory-confirmed novel swine-origin influenza A (H1N1) virus (S-OIV) infection and detect pneumonia earlier. Materials and methods: High-resolution CT (HRCT) findings of 106 patients with presumed/laboratory-confirmed novel S-OIV (H1N1) infection were reviewed. The 106 patients were divided into two groups according to the serious condition of the diseases. The pattern (consolidation, ground-glass, nodules, and reticulation), distribution, and extent of abnormality on the HRCT were evaluated in both groups. The dates of the onset of symptoms of the patients were recorded. Results: The predominant CT findings in the patients at presentation were unilateral or bilateral multifocal asymmetric ground-glass opacities alone (n = 29, 27.4%), with unilateral or bilateral consolidation (n = 50, 47.2%). The consolidation had peribronchovascular and subpleural predominance. The areas of consolidation were found mainly in the posterior, middle and lower regions of the lungs. Reticular opacities were found in 6 cases of the initial MDCT scan. The extent of disease was greater in group 1 patients requiring advanced mechanical ventilation, with diffuse involvement in 19 patients (63.3%) of group 1 patients, and only 15/76 (19.7%) of group 2 patients (p < 0.01, {chi}{sup 2} test). 20 cases (19%) of the 106 patients had small bilateral or unilateral pleural effusions. None had evidence of hilar or mediastinal lymph node enlargement on CT performed at admission or later. Conclusions: The most common radiographic and CT findings in patients with S-OIV infection are unilateral or bilateral ground-glass opacities with or without associated focal or multifocal areas of consolidation. On HRCT, the ground-glass opacities had a predominant peribronchovascular and subpleural distribution. CT plays an important role in the early recognition of severe S

  17. Hemagglutinin protein of Asian strains of human influenza virus A H1N1 binds to sialic acid--a major component of human airway receptors.

    Science.gov (United States)

    Chua, K H; Chai, H C

    2012-03-16

    Hemagglutinin (HA) protein plays an important role in binding the influenza virus to infected cells and therefore mediates infection. Deposited HA sequences of 86 Asian strains of influenza A (H1N1) viruses during the first outbreak were obtained from the NCBI database and compared. Interaction of the HA protein of influenza A (H1N1) virus with the human sialic acid receptor was also studied using bioinformatics. Overall, not more than three single-point amino acid variants/changes were observed in the HA protein region of influenza A (H1N1) virus from Asian countries when a selected group sequence comparison was made. The bioinformatics study showed that the HA protein of influenza A (H1N1) binds to the sialic acid receptor in human airway receptors, possibly key to air-borne infection in humans.

  18. Next generation syndromic surveillance: molecular epidemiology, electronic health records and the pandemic Influenza A (H1N1) virus.

    Science.gov (United States)

    Rabadan, Raul; Calman, Neil; Hripcsak, George

    2009-08-22

    In the early phase of the 2009 A (H1N1) pandemic a marked increase in severity and a shift in the age distribution toward younger persons was found, with higher severity reported in patients with pre-existing medical conditions and pregnant women. Consistent with previous pandemics, the age and clinical history of the patients play a critical role in the morbidity and mortality associated with the pandemic virus. This is the first influenza pandemic in the information era, where enormous amounts of information will be available from the pathogen and the patient. Recent advances in molecular techniques have provided an enormous amount of information about pathogens in near real time and at relatively low cost. Electronic Health Records (EHRs) provide another enormously rich set of information about patients, which include patient preconditions, previous exposures, immunization history, presenting complaints, duration and severity of illness, treatment history, and geographic location. An infectious disease is a complex interplay between host and pathogen. The morbidity and mortality of a virus depend on the virus, the patient, and the environment. To evaluate and understand the severity of the pandemic virus and to identify the populations at risk of mild or severe, life-threatening illness, it is compulsory to integrate viral and patient information in a fast and accurate way. Both advances in biomedical informatics with the creation of EHRs and molecular techniques provide the framework to achieve these aims.

  19. Genetic Characterization of H1N1 and H1N2 Influenza A Viruses Circulating in Ontario Pigs in 2012.

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    Helena Grgić

    Full Text Available The objective of this study was to characterize H1N1 and H1N2 influenza A virus isolates detected during outbreaks of respiratory disease in pig herds in Ontario (Canada in 2012. Six influenza viruses were included in analysis using full genome sequencing based on the 454 platform. In five H1N1 isolates, all eight segments were genetically related to 2009 pandemic virus (A(H1N1pdm09. One H1N2 isolate had hemagglutinin (HA, polymerase A (PA and non-structural (NS genes closely related to A(H1N1pdm09, and neuraminidase (NA, matrix (M, polymerase B1 (PB1, polymerase B2 (PB2, and nucleoprotein (NP genes originating from a triple-reassortant H3N2 virus (tr H3N2. The HA gene of five Ontario H1 isolates exhibited high identity of 99% with the human A(H1N1pdm09 [A/Mexico/InDRE4487/09] from Mexico, while one Ontario H1N1 isolate had only 96.9% identity with this Mexican virus. Each of the five Ontario H1N1 viruses had between one and four amino acid (aa changes within five antigenic sites, while one Ontario H1N2 virus had two aa changes within two antigenic sites. Such aa changes in antigenic sites could have an effect on antibody recognition and ultimately have implications for immunization practices. According to aa sequence analysis of the M2 protein, Ontario H1N1 and H1N2 viruses can be expected to offer resistance to adamantane derivatives, but not to neuraminidase inhibitors.

  20. Genetic Characterization of H1N1 and H1N2 Influenza A Viruses Circulating in Ontario Pigs in 2012.

    Science.gov (United States)

    Grgić, Helena; Costa, Marcio; Friendship, Robert M; Carman, Susy; Nagy, Éva; Poljak, Zvonimir

    2015-01-01

    The objective of this study was to characterize H1N1 and H1N2 influenza A virus isolates detected during outbreaks of respiratory disease in pig herds in Ontario (Canada) in 2012. Six influenza viruses were included in analysis using full genome sequencing based on the 454 platform. In five H1N1 isolates, all eight segments were genetically related to 2009 pandemic virus (A(H1N1)pdm09). One H1N2 isolate had hemagglutinin (HA), polymerase A (PA) and non-structural (NS) genes closely related to A(H1N1)pdm09, and neuraminidase (NA), matrix (M), polymerase B1 (PB1), polymerase B2 (PB2), and nucleoprotein (NP) genes originating from a triple-reassortant H3N2 virus (tr H3N2). The HA gene of five Ontario H1 isolates exhibited high identity of 99% with the human A(H1N1)pdm09 [A/Mexico/InDRE4487/09] from Mexico, while one Ontario H1N1 isolate had only 96.9% identity with this Mexican virus. Each of the five Ontario H1N1 viruses had between one and four amino acid (aa) changes within five antigenic sites, while one Ontario H1N2 virus had two aa changes within two antigenic sites. Such aa changes in antigenic sites could have an effect on antibody recognition and ultimately have implications for immunization practices. According to aa sequence analysis of the M2 protein, Ontario H1N1 and H1N2 viruses can be expected to offer resistance to adamantane derivatives, but not to neuraminidase inhibitors.

  1. Oseltamivir for treatment and prevention of pandemic influenza A/H1N1 virus infection in households, Milwaukee, 2009

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    Miller Joel C

    2010-07-01

    Full Text Available Abstract Background During an influenza pandemic, a substantial proportion of transmission is thought to occur in households. We used data on influenza progression in individuals and their contacts collected by the City of Milwaukee Health Department (MHD to study the transmission of pandemic influenza A/H1N1 virus in 362 households in Milwaukee, WI, and the effects of oseltamivir treatment and chemoprophylaxis. Methods 135 households had chronological information on symptoms and oseltamivir usage for all household members. The effect of oseltamivir treatment and other factors on the household secondary attack rate was estimated using univariate and multivariate logistic regression with households as the unit of analysis. The effect of oseltamivir treatment and other factors on the individual secondary attack rate was estimated using univariate and multivariate logistic regression with individual household contacts as the unit of analysis, and a generalized estimating equations approach was used to fit the model to allow for clustering within households. Results Oseltamivir index treatment on onset day or the following day (early treatment was associated with a 42% reduction (OR: 0.58, 95% CI: 0.19, 1.73 in the odds of one or more secondary infections in a household and a 50% reduction (OR: 0.5, 95% CI: 0.17, 1.46 in the odds of a secondary infection in individual contacts. The confidence bounds are wide due to a small sample of households with early oseltamivir index usage - in 29 such households, 5 had a secondary attack. Younger household contacts were at higher risk of infection (OR: 2.79, 95% CI: 1.50-5.20. Conclusions Early oseltamivir treatment may be beneficial in preventing H1N1pdm influenza transmission; this may have relevance to future control measures for influenza pandemics. Larger randomized trials are needed to confirm this finding statistically.

  2. Pandemic Influenza A (H1N1) Virus Infection Increases Apoptosis and HIV-1 Replication in HIV-1 Infected Jurkat Cells.

    Science.gov (United States)

    Wang, Xue; Tan, Jiying; Biswas, Santanu; Zhao, Jiangqin; Devadas, Krishnakumar; Ye, Zhiping; Hewlett, Indira

    2016-02-02

    Influenza virus infection has a significant impact on public health, since it is a major cause of morbidity and mortality. It is not well-known whether influenza virus infection affects cell death and human immunodeficiency virus (HIV)-1 replication in HIV-1-infected patients. Using a lymphoma cell line, Jurkat, we examined the in vitro effects of pandemic influenza A (H1N1) virus (pH1N1) infection on cell death and HIV-1 RNA production in infected cells. We found that pH1N1 infection increased apoptotic cell death through Fas and Bax-mediated pathways in HIV-1-infected Jurkat cells. Infection with pH1N1 virus could promote HIV-1 RNA production by activating host transcription factors including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-ĸB), nuclear factor of activated T-cells (NFAT) and activator protein 1 (AP-1) through mitogen-activated protein kinases (MAPK) pathways and T-cell antigen receptor (TCR)-related pathways. The replication of HIV-1 latent infection could be reactivated by pH1N1 infection through TCR and apoptotic pathways. These data indicate that HIV-1 replication can be activated by pH1N1 virus in HIV-1-infected cells resulting in induction of cell death through apoptotic pathways.

  3. Fatal acute myocarditis and fulminant hepatic failure in an infant with pandemic human influenza A, H1N1 (2009 virus infection

    Directory of Open Access Journals (Sweden)

    Mortada H.F. El-Shabrawi

    2011-04-01

    Full Text Available We report the clinical presentation of a 10 month-old infant who succumbed with acute myocarditis and fulminant hepatic failure associated with a virologically confirmed human influenza A, H1N1 (2009 virus infection. To date, this is the first pediatric patient presenting with this fatal combination of complications during the current H1N1 pandemic. Therefore, we recommend meticulous assessment and follow up of the cardiac status, liver enzymes and coagulation profile in all pediatric patients with severe H1N1 influenza infection.

  4. Detection of Seasonal Influenza H1N1 and H3N2 Viruses using RT-PCR Assay during 2009 Pandemic Influenza in Golestan Province

    Directory of Open Access Journals (Sweden)

    Zhand, S. (MSc

    2014-05-01

    Full Text Available Background and Objective: The emergence of a novel H1N1influenza A virus of animal origin with transmissibility from human to human poses pandemic concern. Current subtypes of Seasonal influenza A viruses spread in human are influenza A H1N1 influenza A H3N2 and influenza type B viruses. The aim of this study was to determine current strains of the H3N2 and new H1N1 subtypes of influenza A virus from patients suspected influenza infection in 2009 flu pandemic in Golestan province, Iran. Material and Methods: In this descriptive study, respiratory samples (n = 153 from patients with acute respiratory symptoms were collected in 2009 flu pandemic applied during 2009 pandemic influenza in Golestan province. After reverse transcription of extracted viral RNA, PCR was developed for both H1N1and H3N2subtypes using CDC specific primers. Results: The mean age of patients was 16.59. Of them 45.1% were male. Thirteen (8.49% were infected with seasonal influenza H1N1 and 25(16.33% with seasonal H3N2influenza. Conclusion: The rate of infection with seasonal H1N1and H3N2is similar to other studies reported from Iran, but lower than the rate reported from other parts of the world

  5. Spillback transmission of European H1N1 avian-like swine influenza viruses to turkeys: A strain-dependent possibility?

    Science.gov (United States)

    Bonfante, Francesco; Fusaro, Alice; Tassoni, Luca; Patrono, Livia Victoria; Milani, Adelaide; Maniero, Silvia; Salviato, Annalisa; Terregino, Calogero

    2016-04-15

    In 1979, an avian influenza virus of the H1N1 subtype began to circulate in European swine herds, rapidly replacing classical swine H1N1 viruses. Spill-back transmissions to turkeys were recorded occasionally, but they might have been underreported due to the asymptomatic nature of the infection and the lack of specific surveillance. In our study, we evaluated the infectivity and transmissibility in turkeys of seven strains of H1N1 avian-like swine viruses isolated from 1979 to 2006, and compared them with their closest progenitor A/duck/Bavaria/1/77 (H1N1), to establish whether the adaptation to pigs has gradually decreased their fitness in turkeys. Our data indicate that the circulation of European H1N1 in pigs might have impaired the possibility of infecting turkeys. Nevertheless, the two swine-origin strains, which showed the ability to replicate and transmit in turkeys, possess typical swine-like genetic traits, not different from the rest of the tested isolates, suggesting replication of avian-like swine H1N1 viruses in turkeys as a strain-dependent polygenic feature.

  6. Novel Influenza A (H1N1/09) Virus Infection during Pregnancy in a Kidney Transplant Recipient

    OpenAIRE

    2011-01-01

    We report the first case of a pregnant renal transplant patient with H1N1/09 infection. The woman showed a mild clinical course after diagnosis of H1N1/09 infection and therapy with oseltamivir (2 × 45 mg per day). After delivery by cesarean section, the neonate exhibited moderate respiratory and circulatory dysregulation, which spontaneously normalised a few days postpartum. In conclusion, rapid diagnosis of H1N1/09 and dose-adapted therapy with oseltamivir resulted in successful delivery of...

  7. Fatal acute myocarditis and fulminant hepatic failure in an infant with pandemic human influenza A, H1N1 (2009) virus infection

    OpenAIRE

    Mortada H.F. El-Shabrawi; Bazaraa, Hafez M; Hanan Zekri; Hanaa I. Rady

    2011-01-01

    We report the clinical presentation of a 10 month-old infant who succumbed with acute myocarditis and fulminant hepatic failure associated with a virologically confirmed human influenza A, H1N1 (2009) virus infection. To date, this is the first pediatric patient presenting with this fatal combination of complications during the current H1N1 pandemic. Therefore, we recommend meticulous assessment and follow up of the cardiac status, liver enzymes and coagulation profile in all pediatric patien...

  8. Avian influenza viruses that cause highly virulent infections in humans exhibit distinct replicative properties in contrast to human H1N1 viruses

    Science.gov (United States)

    Simon, Philippe F.; de La Vega, Marc-Antoine; Paradis, Éric; Mendoza, Emelissa; Coombs, Kevin M.; Kobasa, Darwyn; Beauchemin, Catherine A. A.

    2016-04-01

    Avian influenza viruses present an emerging epidemiological concern as some strains of H5N1 avian influenza can cause severe infections in humans with lethality rates of up to 60%. These have been in circulation since 1997 and recently a novel H7N9-subtyped virus has been causing epizootics in China with lethality rates around 20%. To better understand the replication kinetics of these viruses, we combined several extensive viral kinetics experiments with mathematical modelling of in vitro infections in human A549 cells. We extracted fundamental replication parameters revealing that, while both the H5N1 and H7N9 viruses replicate faster and to higher titers than two low-pathogenicity H1N1 strains, they accomplish this via different mechanisms. While the H7N9 virions exhibit a faster rate of infection, the H5N1 virions are produced at a higher rate. Of the two H1N1 strains studied, the 2009 pandemic H1N1 strain exhibits the longest eclipse phase, possibly indicative of a less effective neuraminidase activity, but causes infection more rapidly than the seasonal strain. This explains, in part, the pandemic strain’s generally slower growth kinetics and permissiveness to accept mutations causing neuraminidase inhibitor resistance without significant loss in fitness. Our results highlight differential growth properties of H1N1, H5N1 and H7N9 influenza viruses.

  9. H1N1 Influenza

    Science.gov (United States)

    ... Nutrient Shortfall Questionnaire Home Diseases and Conditions H1N1 Influenza H1N1 Influenza Condition Family HealthKids and Teens Share H1N1 ... Contents1. Overview2. Symptoms3. Prevention4. Treatment What is H1N1 influenza?H1N1 influenza (also known as swine flu) is an ...

  10. Influenza A/H1N1/2009 virus - experience of the clinical microbiology laboratory of the “L. Sacco” University Hospital in Milan

    Directory of Open Access Journals (Sweden)

    Lisa Lucia Chenal

    2011-06-01

    Full Text Available In the spring of 2009, a new variant of influenza A/H1N1 virus that had never been isolated before, was identified. From April 27 to December 31, 2009 the respiratory samples of 974 patients, obtained from suspected cases of pandemic influenza A virus infection, were analyzed at the Clinical Microbiology Laboratory of the “L. Sacco” University Hospital in Milan. The diagnosis of influenza A/H1N1 infection was performed initially through the use of different molecular biological methods: Seeplex® RV12 ACE Detection (Seegene, NUCLISENS® EASYQ® INFLUENZA A/B (bioMérieux, Influenza A/B Q-PCR Alert (Nanogen running in parallel with rRT-PCR (CDC to confirm the positivity to the new influenza virus, then was used a single specific test, Fast set H1N1v (Arrow Diagnostics. Retrospective study of data showed that 293 (30.1% patients were positive for the new strain of influenza A/H1N1 virus and 8 (0.8% for influenza A other than H1N1 virus.The distribution of influenza A/H1N1 cases showed two peaks, one on July (62.9% and the other one on October (36%, moreover we observed that 155 patients (53% out of 293 positive for influenza A/H1N1 virus aged under 20 years old. The first positivity peak was found in travelers and the second one, occurred 2-3 months prior to the classic seasonal epidemic influenza, was attributed to autochthonous cases , by which the virus had spread worldwide. The highest proportion of cases were among subjects aged from 0 to 20 years and, over this age the positivity rate decreased proportionally with increasing age, in agreement with data reported in other countries.

  11. Protection of human influenza vaccines against a reassortant swine influenza virus of pandemic H1N1 origin using a pig model.

    Science.gov (United States)

    Arunorat, Jirapat; Charoenvisal, Nataya; Woonwong, Yonlayong; Kedkovid, Roongtham; Jittimanee, Supattra; Sitthicharoenchai, Panchan; Kesdangsakonwut, Sawang; Poolperm, Pariwat; Thanawongnuwech, Roongroje

    2017-02-28

    Since the pandemic H1N1 emergence in 2009 (pdmH1N1), many reassortant pdmH1N1 viruses emerged and found circulating in the pig population worldwide. Currently, commercial human subunit vaccines are used commonly to prevent the influenza symptom based on the WHO recommendation. In case of current reassortant swine influenza viruses transmitting from pigs to humans, the efficacy of current human influenza vaccines is of interest. In this study, influenza A negative pigs were vaccinated with selected commercial human subunit vaccines and challenged with rH3N2. All sera were tested with both HI and SN assays using four representative viruses from the surveillance data in 2012 (enH1N1, pdmH1N1, rH1N2 and rH3N2). The results showed no significant differences in clinical signs and macroscopic and microscopic findings among groups. However, all pig sera from vaccinated groups had protective HI titers to the enH1N1, pdmH1N1 and rH1N2 at 21DPV onward and had protective SN titers only to pdmH1N1and rH1N2 at 21DPV onward. SN test results appeared more specific than those of HI tests. All tested sera had no cross-reactivity against the rH3N2. Both studied human subunit vaccines failed to protect and to stop viral shedding with no evidence of serological reaction against rH3N2. SIV surveillance is essential for monitoring a novel SIV emergence potentially for zoonosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Investigation of Pathogenesis of H1N1 Influenza Virus and Swine Streptococcus suis Serotype 2 Co-Infection in Pigs by Microarray Analysis.

    Science.gov (United States)

    Lin, Xian; Huang, Canhui; Shi, Jian; Wang, Ruifang; Sun, Xin; Liu, Xiaokun; Zhao, Lianzhong; Jin, Meilin

    2015-01-01

    Swine influenza virus and Streptococcus suis are two important contributors to the porcine respiratory disease complex, and both have significant economic impacts. Clinically, influenza virus and Streptococcus suis co-infections in pigs are very common, which often contribute to severe pneumonia and can increase the mortality. However, the co-infection pathogenesis in pigs is unclear. In the present study, co-infection experiments were performed using swine H1N1 influenza virus and Streptococcus suis serotype 2 (SS2). The H1N1-SS2 co-infected pigs exhibited more severe clinical symptoms, serious pathological changes, and robust apoptosis of lungs at 6 days post-infection compared with separate H1N1 and SS2 infections. A comprehensive gene expression profiling using a microarray approach was performed to investigate the global host responses of swine lungs against the swine H1N1 infection, SS2 infection, co-infection, and phosphate-buffered saline control. Results showed 457, 411, and 844 differentially expressed genes in the H1N1, SS2, and H1N1-SS2 groups, respectively, compared with the control. Noticeably, genes associated with the immune, inflammatory, and apoptosis responses were highly overexpressed in the co-infected group. Pathway analysis indicated that the cytokine-cytokine receptor interactions, MAPK, toll-like receptor, complement and coagulation cascades, antigen processing and presentation, and apoptosis pathway were significantly regulated in the co-infected group. However, the genes related to these were less regulated in the separate H1N1 and SS2 infection groups. This observation suggested that a certain level of synergy was induced by H1N1 and SS2 co-infection with significantly stronger inflammatory and apoptosis responses, which may lead to more serious respiratory disease syndrome and pulmonary pathological lesion.

  13. In silico analysis and identification of novel inhibitor for new H1N1 swine influenza virus

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    Manjunath Dammalli

    2014-09-01

    Full Text Available Objective: To identify alternative drug for the treatment of pandemic disease caused by influenza virus. Methods: The structure based drug design approach was employed. New sequence was employed to build the N1 simulation structure by homology modeling which was further checked for high reliability by verify score and Ramachandran plot. Evaluation of drug likeness and absorption, distribution, metabolism, excretion, toxicity showed that the ligands satisfy all the properties to be used as a drug. Docking studies were performed using LeadIT and docking scores indicated good binding energy values towards N1. Results: Four candidates were screened and suggested as potent target candidates from the docking studies. The screened compounds from Stemonaceae family illustrated better activity compared to the drugs which are already present in the market. Conclusions: The results may help to find the alternative drug to solve the drug-resistant problem and stimulate designing more effective drugs against 2009-H1N1 influenza pandemic, yet pharmacological studies have to confirm it.

  14. Evidence of reassortment of pandemic H1N1 influenza virus in swine in Argentina: are we facing the expansion of potential epicenters of influenza emergence?

    Science.gov (United States)

    Pereda, Ariel; Rimondi, Agustina; Cappuccio, Javier; Sanguinetti, Ramon; Angel, Matthew; Ye, Jianqiang; Sutton, Troy; Dibárbora, Marina; Olivera, Valeria; Craig, Maria I.; Quiroga, Maria; Machuca, Mariana; Ferrero, Andrea; Perfumo, Carlos; Perez, Daniel R.

    2011-01-01

    Please cite this paper as: Pereda et al. (2011) Evidence of reassortment of pandemic H1N1 influenza virus in swine in Argentina: are we facing the expansion of potential epicenters of influenza emergence? Influenza and Other Respiratory Viruses 5(6), 409–412. In this report, we describe the occurrence of two novel swine influenza viruses (SIVs) in pigs in Argentina. These viruses are the result of two independent reassortment events between the H1N1 pandemic influenza virus (H1N1pdm) and human‐like SIVs, showing the constant evolution of influenza viruses at the human–swine interface and the potential health risk of H1N1pdm as it appears to be maintained in the swine population. It must be noted that because of the lack of information regarding the circulation of SIVs in South America, we cannot discard the possibility that ancestors of the H1N1pdm or other SIVs have been present in this part of the world. More importantly, these findings suggest an ever‐expanding geographic range of potential epicenters of influenza emergence with public health risks. PMID:21668680

  15. Preparing the outbreak assistance laboratory network in the Netherlands for the detection of the influenza virus A(H1N1) variant

    NARCIS (Netherlands)

    Meijer, Adam; Beerens, Antoine; Claas, Eric; Hermans, Mirjam; de Jong, Arjan; Molenkamp, Richard; Niesters, Hubert; Overduin, Pieter; Rossen, John; Schuurman, Rob; Wolffs, Petra; Fouchier, Ron; Osterhaus, Albert; Schutten, Martin; Koopmans, Marion

    2009-01-01

    BACKGROUND: Late April 2009, human infection with variant influenza virus A(H1N1)v emerged in the Northern Americas posing a threat that this virus may become the next pandemic influenza virus. OBJECTIVES: To prepare laboratories for surge capacity for molecular diagnosis of patients suspected for A

  16. Preparing the outbreak assistance laboratory network in the Netherlands for the detection of the influenza virus A(H1N1) variant.

    NARCIS (Netherlands)

    Meijer, A.; Beerens, A.; Claas, E.; Hermans, M.; Jong, A. de; Molenkamp, R.; Niesters, H.; Overduin, P.; Rossen, J.; Schuurman, R.; Wolffs, P.; Fouchier, R.; Osterhaus, A.; Schutten, M.; Koopmans, M.

    2009-01-01

    BACKGROUND: Late April 2009, human infection with variant influenza virus A(H1N1)v emerged in the Northern Americas posing a threat that this virus may become the next pandemic influenza virus. OBJECTIVES: To prepare laboratories for surge capacity for molecular diagnosis of patients suspected for A

  17. Preparing the outbreak assistance laboratory network in the Netherlands for the detection of the influenza virus A(H1N1) variant

    NARCIS (Netherlands)

    A. Meijer; A. Beerens; E. Claas; M. Hermans; A. de Jong; R. Molenkamp; H. Niesters; P. Overduin; J. Rossen; R. Schuurman; P. Wolffs; R. Fouchier; A. Osterhaus; M. Schutten; M. Koopmans

    2009-01-01

    Background: Late April 2009, human infection with variant influenza virus A(H1N1)v emerged in the Northern Americas posing a threat that this virus may become the next pandemic influenza virus. Objectives: To prepare laboratories for surge capacity for molecular diagnosis of patients suspected for A

  18. Chest radiographic findings in children with 2009 influenza A ( H1N1 ) virus infection%2009甲型H1N1流感儿童胸X线片表现

    Institute of Scientific and Technical Information of China (English)

    闫淯淳; 房萍; 白凤森; 陈慧中; 车莉; 袁新宇; 曲东; 任晓旭; 张宝元; 孙宇

    2011-01-01

    Objective To evaluate chest radiographic findings of children with 2009 influenza ( H1N1 ) virus infection. Method Data of 235 patients who had microbiologically confirmed H1N1 infection and available chest radiograph obtained between May 1st 2009 and Jan. 31st 2010 were retrospectively analyzed. The final study group was divided on the basis of clinical course [group 1 mild, outpatients without hospitalization ( n = 172 ); group 2 moderate, inpatients with brief hospitalization ( n = 49 ); group 3 severe, ICU admission (n = 14)]. Four pediatric radiologists reviewed all the chest radiographs of lung parenchyma, airway, pleural abnormalities and also anatomic distribution of the disease. Result No significant sex or age differences were found among the study groups ( P >0.05 ). The mean interval between the onset of clinical symptom and the initial chest radiography was (5.91 ± 1. 64) days (group 1 ), (3.60 ±1.43 ) days ( group 2) and ( 1.21 ± 0.41 ) days ( group 3 ), respectively. The differences among the three groups were significant statistically ( χ2 = 13.368, P < 0.01 ). The ratio of abnormality presented at initial chest X-ray was 79.7% in group 1,91.8% in group 2 and 100% in group 3. Radiographically, there were prominent peribronchial markings ( group 1, 55.2%; group 2, 83.7%; and group 3, 78.6% ),consolidation ( group 1, 34.3%; group 2, 69.4%; and group 3, 100.0% ), hyperinflation ( group 1,22.1%; group 2, 44.9%; and group 3, 50.0% ) and ground glass opacity ( group 1, 0.6%; group 2,2.0%; and group 3, 14.3% ) in the chest radiographs. The differences of presenting were statistically significant (P <0.01 ). In the severe group, the lesions distributed diffusely and asymmetrically with multi lobe involvements. Conclusion In children with 2009 influenza A H1N1 viral infection, the interval between the onset of clinical symptom and initial chest radiography, the ratio of abnormality presented at initial chest X-ray film and the severity of chest

  19. Effect of human rhinovirus infection in pediatric patients with influenza-like illness on the 2009 pandemic influenza A(H1N1) virus

    Institute of Scientific and Technical Information of China (English)

    Sun Yu; Zhu Ru'nan; Zhao Linqing; Deng Jie; Wang Fang; Ding Yaxin; Yuan Yi

    2014-01-01

    Background Some research groups have hypothesized that human rhinoviruses (HRVs) delayed the circulation of the 2009 pandemic influenza A(H1N1) virus (A(H1N1)pdm09) at the beginning of Autumn 2009 in France.This study aimed to evaluate the relationship between HRV and A(H1N1)pdm09 in pediatric patients with influenza-like illness in Beijing,China.Methods A systematic analysis to detect A(H1N1)pdm09 and seasonal influenza A virus (FLU A) was performed on 4 349 clinical samples from pediatric patients with influenza-like illness during the period June 1,2009 to February 28,2010,while a one-step real-time RT-PCR (rRT-PCR) assay was used to detect HRV in 1 146 clinical specimens selected from those 4 349 specimens.Results During the survey period,only one wave of A(H1N1)pdm09 was observed.The percentage of positive cases for A(H1N1)pdm09 increased sharply in September with a peak in November 2009 and then declined in February 2010.Data on the monthly distribution of HRVs indicated that more HRV-positive samples were detected in September (2.2%) and October (3.3%),revealing that the peak of HRV infection in 2009 was similar to that of other years.Among the 1 146 specimens examined for HRVs,21 (1.8%) were HRV-positive,which was significantly lower than that reported previously in Beijing (15.4% to 19.2%) (P <0.01).Overall,6 samples were positive for both A(H1N1)pdm09 and HRV,which represented a positive relative frequency of 1.60% and 2.08% HRV,considering the A(H1N1)pdm09-positive and-negative specimens,respectively.The odds ratio was 0.87 (95% CI 0.32; 2.44,P=0.80).Conclusions HRVs and A (H1N1)pdm09 co-circulated in this Chinese population during September and October 2009,and the HRV epidemic in 2009 did not affect A(H1N1)pdm09 infection rates in Beijing,China as suggested by other studies.However,the presence of A(H1N1)pdm09 might explain the unexpected reduction in the percentage of HRV positive cases during the period studied.

  20. A whole virus pandemic influenza H1N1 vaccine is highly immunogenic and protective in active immunization and passive protection mouse models.

    Directory of Open Access Journals (Sweden)

    Otfried Kistner

    Full Text Available The recent emergence and rapid spread of a novel swine-derived H1N1 influenza virus has resulted in the first influenza pandemic of this century. Monovalent vaccines have undergone preclinical and clinical development prior to initiation of mass immunization campaigns. We have carried out a series of immunogenicity and protection studies following active immunization of mice, which indicate that a whole virus, nonadjuvanted vaccine is immunogenic at low doses and protects against live virus challenge. The immunogenicity in this model was comparable to that of a whole virus H5N1 vaccine, which had previously been demonstrated to induce high levels of seroprotection in clinical studies. The efficacy of the H1N1 pandemic vaccine in protecting against live virus challenge was also seen to be equivalent to that of the H5N1 vaccine. The protective efficacy of the H1N1 vaccine was also confirmed using a severe combined immunodeficient (SCID mouse model. It was demonstrated that mouse and guinea pig immune sera elicited following active H1N1 vaccination resulted in 100% protection of SCID mice following passive transfer of immune sera and lethal challenge. The immune responses to a whole virus pandemic H1N1 and a split seasonal H1N1 vaccine were also compared in this study. It was demonstrated that the whole virus vaccine induced a balanced Th-1 and Th-2 response in mice, whereas the split vaccine induced mainly a Th-2 response and only minimal levels of Th-1 responses. These data supported the initiation of clinical studies with the same low doses of whole virus vaccine that had previously been demonstrated to be immunogenic in clinical studies with a whole virus H5N1 vaccine.

  1. Similarity of currently circulating H1N1 virus with the 2009 pandemic clone: viability of an imminent pandemic.

    Science.gov (United States)

    Banerjee, Rachana; Roy, Ayan; Das, Santasabuj; Basak, Surajit

    2015-06-01

    The first influenza pandemic in the 21st century commenced in March, 2009 causing nearly 300,000 deaths globally within the first year of the pandemic. In late 2013 and in early 2014, there was gradual increase in the reported case of H1N1 infection and according to World Health Organization (WHO) report, influenza activity increased in several areas of the Southern Hemisphere and was dominated by the H1N1 pandemic strain of 2009. In the present study, a comprehensive comparison of the global amino acid composition and the structural features of all HA gene sequences of H1N1, available in the Flu Database (NCBI), from 1918 to December, 2014 has been performed to trace out the possibility of a further H1N1 pandemic in near future. The results suggest that the increased potential to enhance pathogenicity for the H1N1 samples of 2013 (latter part) and 2014 could lead to a more severe outbreak in the near future.

  2. Surveillance on the levels of antibody to pandemic influenza A(H1N1)2009 virus before and after vaccination with pandemic influenza A(H1N1)2009 vaccines in Shanghai middle school students%上海地区在校中学生接种甲型H1N1流感疫苗前后抗体水平监测分析

    Institute of Scientific and Technical Information of China (English)

    高颖阳; 申惠国; 陈蓓; 杨忠东; 陈浩; 吕锡宏; 居丽雯

    2010-01-01

    Objective To understand the levels of antibody to pandemic influenza A(H1N1)2009 virus before and after vaccination with pandemic influenza A(H1N1)2009 vaccines in Shanghai middle school students, and to observe the protection of pandemic influenza A(H1N1)2009 vaccines for this group.Methods The levels of antibody to pandemic influenza A(H1N1)2009 virus in Shanghai middle school students were determined using the routine micro-hemagglutination inhibition test in three periods, and the positive rates of the antibodies in three periods were compared by Pearson's x2 test. Results Before the epidemic of pandemic influenza A(H1N1)2009, the positive rate of antibody to pandemic influenza A (H1N1)2009 virus among Shanghai middle school students was only 1.3%, and then it increased to 8.5% after a period of epidemic. After vaccination with pandemic influenza A(H1N1)2009 vaccines, the positive rate of antibody to pandemic influenza A(H1N1)2009 virus among middle school students increased to 87.3%. The result of Pearson' sx2 test showed that differences of the positive rate of antibody in three periods had statistical significance(x2 = 243.7, P < 0. 05). Conclusions Before the epidemic of pandemic influenza A(H1N1)2009, Shanghai middle school students almost have no immunity against this new type of virus, and vaccination with pandemic irfluenza A(H1N1)2009 vaccines can provide stronger protection for this group.%目的 了解上海地区在校中学生接种甲型H1N1流感疫苗前后的抗体水平,观察甲型H1N1流感疫苗对该人群的免疫保护作用.方法 应用常规微量血凝抑制试验(micro-hemagglutination inhibition test,HIT)对上海地区在校中学生分3个时间段进行甲型H1N1流感病毒抗体的血清学监测,3个时间段的抗体阳性率比较采用Pearson x2检验进行分析.结果 2009年甲型H1N1流感流行前上海地区在校中学生的血清抗体阳性率仅为1.3%.经过一段时间流行后,血清抗体阳性率升至8

  3. An H5N1 M2e-based multiple antigenic peptide vaccine confers heterosubtypic protection from lethal infection with pandemic 2009 H1N1 virus

    Directory of Open Access Journals (Sweden)

    Yu Hong

    2010-07-01

    Full Text Available Abstract Background A 2009 global influenza pandemic caused by a novel swine-origin H1N1 influenza A virus has posted an increasing threat of a potential pandemic by the highly pathogenic avian influenza (HPAI H5N1 virus, driving us to develop an influenza vaccine which confers cross-protection against both H5N1 and H1N1 viruses. Previously, we have shown that a tetra-branched multiple antigenic peptide (MAP vaccine based on the extracellular domain of M2 protein (M2e from H5N1 virus (H5N1-M2e-MAP induced strong immune responses and cross-protection against different clades of HPAI H5N1 viruses. In this report, we investigated whether such M2e-MAP presenting the H5N1-M2e consensus sequence can afford heterosubtypic protection from lethal challenge with the pandemic 2009 H1N1 virus. Results Our results demonstrated that H5N1-M2e-MAP plus Freund's or aluminum adjuvant induced strong cross-reactive IgG antibody responses against M2e of the pandemic H1N1 virus which contains one amino acid variation with M2e of H5N1 at position 13. These cross-reactive antibodies may maintain for 6 months and bounced back quickly to the previous high level after the 2nd boost administered 2 weeks before virus challenge. H5N1-M2e-MAP could afford heterosubtypic protection against lethal challenge with pandemic H1N1 virus, showing significant decrease of viral replications and obvious alleviation of histopathological damages in the challenged mouse lungs. 100% and 80% of the H5N1-M2e-MAP-vaccinated mice with Freund's and aluminum adjuvant, respectively, survived the lethal challenge with pandemic H1N1 virus. Conclusions Our results suggest that H5N1-M2e-MAP has a great potential to prevent the threat from re-emergence of pandemic H1N1 influenza and possible novel influenza pandemic due to the reassortment of HPAI H5N1 virus with the 2009 swine-origin H1N1 influenza virus.

  4. Preventive Activity against Influenza (H1N1 Virus by Intranasally Delivered RNA-Hydrolyzing Antibody in Respiratory Epithelial Cells of Mice

    Directory of Open Access Journals (Sweden)

    Seungchan Cho

    2015-09-01

    Full Text Available The antiviral effect of a catalytic RNA-hydrolyzing antibody, 3D8 scFv, for intranasal administration against avian influenza virus (H1N1 was described. The recombinant 3D8 scFv protein prevented BALB/c mice against H1N1 influenza virus infection by degradation of the viral RNA genome through its intrinsic RNA-hydrolyzing activity. Intranasal administration of 3D8 scFv (50 μg/day for five days prior to infection demonstrated an antiviral activity (70% survival against H1N1 infection. The antiviral ability of 3D8 scFv to penetrate into epithelial cells from bronchial cavity via the respiratory mucosal layer was confirmed by immunohistochemistry, qRT-PCR, and histopathological examination. The antiviral activity of 3D8 scFv against H1N1 virus infection was not due to host immune cytokines or chemokines, but rather to direct antiviral RNA-hydrolyzing activity of 3D8 scFv against the viral RNA genome. Taken together, our results suggest that the RNase activity of 3D8 scFv, coupled with its ability to penetrate epithelial cells through the respiratory mucosal layer, directly prevents H1N1 virus infection in a mouse model system.

  5. Apios americana Medik Extract Alleviates Lung Inflammation in Influenza Virus H1N1- and Endotoxin-Induced Acute Lung Injury.

    Science.gov (United States)

    Sohn, Sung-Hwa; Lee, Sang-Yeon; Cui, Jun; Jang, Ho Hee; Kang, Tae-Hoon; Kim, Jong-Keun; Kim, In-Kyoung; Lee, Deuk-Ki; Choi, Seulgi; Yoon, Il-Sub; Chung, Ji-Woo; Nam, Jae-Hwan

    2015-12-28

    Apios americana Medik (hereinafter Apios) has been reported to treat diseases, including cancer, hypertension, obesity, and diabetes. The therapeutic effect of Apios is likely to be associated with its anti-inflammatory activity. This study was conducted to evaluate the protective effects of Apios in animal models of acute lung injury induced by lipopolysaccharide (LPS) or pandemic H1N1 2009 influenza A virus (H1N1). Mice were exposed to LPS or H1N1 for 2-4 days to induce acute lung injury. The treatment groups were administered Apios extracts via oral injection for 8 weeks before LPS treatment or H1N1 infection. To investigate the effects of Apios, we assessed the mice for in vivo effects of Apios on immune cell infiltration and the level of pro-inflammatory cytokines in the bronchoalveolar lavage (BAL) fluid, and histopathological changes in the lung. After induction of acute lung injury, the numbers of neutrophils and total cells were lower in the Apios-treated groups than in the non-Apios-treated LPS and H1N1 groups. The Apios groups tended to have lower levels of tumor necrosis factor-a and interleukin-6 in BAL fluid. In addition, the histopathological changes in the lungs were markedly reduced in the Apios-treated groups. These data suggest that Apios treatment reduces LPS- and H1N1-induced lung inflammation. These protective effects of Apios suggest that it may have therapeutic potential in acute lung injury.

  6. Novel Influenza A (H1N1/09 Virus Infection during Pregnancy in a Kidney Transplant Recipient

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    Lars Rothermund

    2011-01-01

    Full Text Available We report the first case of a pregnant renal transplant patient with H1N1/09 infection. The woman showed a mild clinical course after diagnosis of H1N1/09 infection and therapy with oseltamivir (2×45 mg per day. After delivery by cesarean section, the neonate exhibited moderate respiratory and circulatory dysregulation, which spontaneously normalised a few days postpartum. In conclusion, rapid diagnosis of H1N1/09 and dose-adapted therapy with oseltamivir resulted in successful delivery of a healthy infant in our renal transplanted patient but emphasized the need for consequent vaccination strategies in pregnant transplant recipients for new influenza A pandemics in the future.

  7. TGF-β Blood Levels Distinguish Between Influenza A (H1N1)pdm09 Virus Sepsis and Sepsis due to Other Forms of Community-Acquired Pneumonia

    Science.gov (United States)

    Rendón-Ramirez, Erick J.; Ortiz-Stern, Alejandro; Martinez-Mejia, Corazon; Salinas-Carmona, Mario C.; Rendon, Adrian; Mata-Tijerina, Viviana L.

    2015-01-01

    Abstract There is a strong interest in finding adequate biomarkers to aid in the diagnosis and prognosis of influenza A (H1N1)pdm09 virus infection. In this study, serum levels of inflammatory cytokines and laboratory markers were evaluated to assess their usefulness as biomarkers of influenza A (H1N1)pdm09 and their association with fatal cases. Serum samples of consecutive patients with a clinical presentation suggestive of influenza A (H1N1)pdm09 and progression to sepsis were evaluated. Serum inflammatory cytokines and routine laboratory tests were performed and correlated with positivity for influenza A (H1N1)pdm09 influenza by real time reverse transcription polymerase chain reaction and the results of three clinical severity scores (Sequential Organ Failure Assessment [SOFA], CURB-65, and Acute Physiology and Chronic Health Evaluation II [APACHE II]). High SOFA scores and some of its individual components, but not CURB-65 or APACHE II scores, correlate with fatal cases regardless of etiology. Total and unconjugated bilirubin, Ca++, Cl−, prothrombin times, and partial thromboplastin times discriminate influenza A (H1N1)pdm09 from other causes of community-acquired pneumonia. High levels of IL-8, IL-10, and IL-17 were increased in influenza A (H1N1)pdm09 patients when compared with controls (p<0.05). IL-6 levels were significantly elevated in influenza A (H1N1)pdm09 patients and non-(H1N1)pdm09 patients when compared with controls (p<0.05). TGF-β serum levels discern between healthy controls, influenza A (H1N1)pdm09 patients, and patients with other causes of community-acquired pneumonia. TGF-β levels were negatively correlated with SOFA on admission in influenza A (H1N1)pdm09 patients. TGF-β levels are a useful tool for differentiating influenza A (H1N1)pdm09 from other causes of pneumonia progressing to sepsis. PMID:25923384

  8. Continual Reintroduction of Human Pandemic H1N1 Influenza A Viruses into Swine in the United States, 2009 to 2014.

    Science.gov (United States)

    Nelson, Martha I; Stratton, Jered; Killian, Mary Lea; Janas-Martindale, Alicia; Vincent, Amy L

    2015-06-01

    The diversity of influenza A viruses in swine (swIAVs) presents an important pandemic threat. Knowledge of the human-swine interface is particularly important for understanding how viruses with pandemic potential evolve in swine hosts. Through phylogenetic analysis of contemporary swIAVs in the United States, we demonstrate that human-to-swine transmission of pandemic H1N1 (pH1N1) viruses has occurred continuously in the years following the 2009 H1N1 pandemic and has been an important contributor to the genetic diversity of U.S. swIAVs. Although pandemic H1 and N1 segments had been largely removed from the U.S. swine population by 2013 via reassortment with other swIAVs, these antigens reemerged following multiple human-to-swine transmission events during the 2013-2014 seasonal epidemic. These findings indicate that the six internal gene segments from pH1N1 viruses are likely to be sustained long term in the U.S. swine population, with periodic reemergence of pandemic hemagglutinin (HA) and neuraminidase (NA) segments in association with seasonal pH1N1 epidemics in humans. Vaccinating U.S. swine workers may reduce infection of both humans and swine and in turn limit the role of humans as sources of influenza virus diversity in pigs. Swine are important hosts in the evolution of influenza A viruses with pandemic potential. Here, we analyze influenza virus sequence data generated by the U.S. Department of Agriculture's national surveillance system to identify the central role of humans in the reemergence of pandemic H1N1 (pH1N1) influenza viruses in U.S. swine herds in 2014. These findings emphasize the important role of humans as continuous sources of influenza virus diversity in swine and indicate that influenza viruses with pandemic HA and NA segments are likely to continue to reemerge in U.S. swine in association with seasonal pH1N1 epidemics in humans. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  9. The Primary Exploration of Enrichment Methods for Influenza A (H1N1) Virus%检测甲型H1N1流感病毒富集方法的初步探索

    Institute of Scientific and Technical Information of China (English)

    李华; 柯华昕; 龙润乡; 杨蓉; 何春艳; 白慧珠; 崔萍芳; 谢忠平

    2010-01-01

    目的 探索甲型H1N1流感病毒的富集方法,提高流感病毒核酸检测的灵敏度.方法 分别用ProteinA/G及H1N1特异性血清处理流感病毒样品,根据国家流感中心设计的H1N1亚型检测通用引物,采用反转录-聚合酶链反应(RT-PCR)方法,扩增产物为527bp,来评价病毒的富集效果.结果 两种富集方法均能提高检测灵敏度,用ProteinA/G富集处理后检测灵敏度可达10-6,用H1N1特异性血清沉淀富集处理后灵敏度为10-5.结论 初步建立的富集甲型H1N1流感病毒方法,有效提高了流感病毒RT-PCR检测的灵敏度,可用于甲型H1N1流感病毒的检测.

  10. TNF, IL6, and IL1B Polymorphisms Are Associated with Severe Influenza A (H1N1 Virus Infection in the Mexican Population.

    Directory of Open Access Journals (Sweden)

    Román Alejandro García-Ramírez

    Full Text Available Hypercytokinemia is the main immunopathological mechanism contributing to a more severe clinical course in influenza A (H1N1 virus infections. Most patients infected with the influenza A (H1N1 pdm09 virus had increased systemic levels of pro-inflammatory cytokines; including interleukin IL-6, IL-8, and tumor necrosis factor-alpha (TNF-α. We propose that single-nucleotide polymorphisms (SNPs in the promoter regions of pro-inflammatory genes are associated with the severity of influenza A (H1N1 pdm09 virus infection.145 patients with influenza A (H1N1 (pA/H1N1, 133 patients with influenza-like illness (ILI, and 360 asymptomatic healthy contacts (AHCs were included. Eleven SNPs were genotyped in six genes (TNF, LT, IL1B, IL6, CCL1, and IL8 using real-time PCR; the ancestral genotype was used for comparison. Genotypes were correlated with 27 clinical severity variables. Ten cytokines (GM-CSF, TNF-α, IL-2, IL-1β, IL-6, IL-8, IFN-γ, IL-10, IL-5, and IL-4 were measured on a Luminex 100.The IL6 rs1818879 (GA heterozygous genotype was associated with severe influenza A (H1N1 virus infection (odds ratio [OR] = 5.94, 95% confidence interval [CI] 3.05-11.56, and two IL1B SNPs, rs16944 AG and rs3136558 TC, were associated with a decreased risk of infection (OR = 0.52 and OR = 0.51, respectively. Genetic susceptibility was determined (pA/H1N1 vs. AHC: the LTA rs909253 TC heterozygous genotype conferred greater risk (OR = 1.9, and a similar association was observed with the IL1B rs3136558 CC genotype (OR = 1.89. Additionally, severely ill patients were compared with moderately ill patients. The TNF-238 GA genotype was associated with an increased risk of disease severity (OR = 16.06, p = 0.007. Compared with ILIs, patients with severe pA/H1N1 infections exhibited increased serum IL-5 (p <0.001 and IL-6 (p  =  0.007 levels.The TNF gene was associated with disease severity, whereas IL1B and IL6 SNPs were associated with influenza A (H1N1 virus

  11. TNF, IL6, and IL1B Polymorphisms Are Associated with Severe Influenza A (H1N1) Virus Infection in the Mexican Population

    Science.gov (United States)

    García-Ramírez, Román Alejandro; Ramírez-Venegas, Alejandra; Quintana-Carrillo, Roger; Camarena, Ángel Eduardo; Falfán-Valencia, Ramcés; Mejía-Aranguré, Juan Manuel

    2015-01-01

    Background Hypercytokinemia is the main immunopathological mechanism contributing to a more severe clinical course in influenza A (H1N1) virus infections. Most patients infected with the influenza A (H1N1) pdm09 virus had increased systemic levels of pro-inflammatory cytokines; including interleukin IL-6, IL-8, and tumor necrosis factor-alpha (TNF-α). We propose that single-nucleotide polymorphisms (SNPs) in the promoter regions of pro-inflammatory genes are associated with the severity of influenza A (H1N1) pdm09 virus infection. Methods 145 patients with influenza A (H1N1) (pA/H1N1), 133 patients with influenza-like illness (ILI), and 360 asymptomatic healthy contacts (AHCs) were included. Eleven SNPs were genotyped in six genes (TNF, LT, IL1B, IL6, CCL1, and IL8) using real-time PCR; the ancestral genotype was used for comparison. Genotypes were correlated with 27 clinical severity variables. Ten cytokines (GM-CSF, TNF-α, IL-2, IL-1β, IL-6, IL-8, IFN-γ, IL-10, IL-5, and IL-4) were measured on a Luminex 100. Results The IL6 rs1818879 (GA) heterozygous genotype was associated with severe influenza A (H1N1) virus infection (odds ratio [OR] = 5.94, 95% confidence interval [CI] 3.05–11.56), and two IL1B SNPs, rs16944 AG and rs3136558 TC, were associated with a decreased risk of infection (OR = 0.52 and OR = 0.51, respectively). Genetic susceptibility was determined (pA/H1N1 vs. AHC): the LTA rs909253 TC heterozygous genotype conferred greater risk (OR = 1.9), and a similar association was observed with the IL1B rs3136558 CC genotype (OR = 1.89). Additionally, severely ill patients were compared with moderately ill patients. The TNF-238 GA genotype was associated with an increased risk of disease severity (OR = 16.06, p = 0.007). Compared with ILIs, patients with severe pA/H1N1 infections exhibited increased serum IL-5 (p <0.001) and IL-6 (p  =  0.007) levels. Conclusions The TNF gene was associated with disease severity, whereas IL1B and IL6 SNPs were

  12. PD-L1 expression induced by the 2009 pandemic influenza A(H1N1) virus impairs the human T cell response.

    Science.gov (United States)

    Valero-Pacheco, Nuriban; Arriaga-Pizano, Lourdes; Ferat-Osorio, Eduardo; Mora-Velandia, Luz María; Pastelin-Palacios, Rodolfo; Villasís-Keever, Miguel Ángel; Alpuche-Aranda, Celia; Sánchez-Torres, Luvia Enid; Isibasi, Armando; Bonifaz, Laura; López-Macías, Constantino

    2013-01-01

    PD-L1 expression plays a critical role in the impairment of T cell responses during chronic infections; however, the expression of PD-L1 on T cells during acute viral infections, particularly during the pandemic influenza virus (A(H1N1)pdm09), and its effects on the T cell response have not been widely explored. We found that A(H1N1)pdm09 virus induced PD-L1 expression on human dendritic cells (DCs) and T cells, as well as PD-1 expression on T cells. PD-L1 expression impaired the T cell response against A(H1N1)pdm09 by promoting CD8⁺ T cell death and reducing cytokine production. Furthermore, we found increased PD-L1 expression on DCs and T cells from influenza-infected patients from the first and second 2009 pandemic waves in Mexico City. PD-L1 expression on CD8⁺ T cells correlated inversely with T cell proportions in patients infected with A(H1N1)pdm09. Therefore, PD-L1 expression on DCs and T cells could be associated with an impaired T cell response during acute infection with A(H1N1)pdm09 virus.

  13. PD-L1 Expression Induced by the 2009 Pandemic Influenza A(H1N1 Virus Impairs the Human T Cell Response

    Directory of Open Access Journals (Sweden)

    Nuriban Valero-Pacheco

    2013-01-01

    Full Text Available PD-L1 expression plays a critical role in the impairment of T cell responses during chronic infections; however, the expression of PD-L1 on T cells during acute viral infections, particularly during the pandemic influenza virus (A(H1N1pdm09, and its effects on the T cell response have not been widely explored. We found that A(H1N1pdm09 virus induced PD-L1 expression on human dendritic cells (DCs and T cells, as well as PD-1 expression on T cells. PD-L1 expression impaired the T cell response against A(H1N1pdm09 by promoting CD8+ T cell death and reducing cytokine production. Furthermore, we found increased PD-L1 expression on DCs and T cells from influenza-infected patients from the first and second 2009 pandemic waves in Mexico City. PD-L1 expression on CD8+ T cells correlated inversely with T cell proportions in patients infected with A(H1N1pdm09. Therefore, PD-L1 expression on DCs and T cells could be associated with an impaired T cell response during acute infection with A(H1N1pdm09 virus.

  14. Systematic review of influenza A(H1N1)pdm09 virus shedding: duration is affected by severity, but not age.

    Science.gov (United States)

    Fielding, James E; Kelly, Heath A; Mercer, Geoffry N; Glass, Kathryn

    2014-03-01

    Duration of viral shedding following infection is an important determinant of disease transmission, informing both control policies and disease modelling. We undertook a systematic literature review of the duration of influenza A(H1N1)pdm09 virus shedding to examine the effects of age, severity of illness and receipt of antiviral treatment. Studies were identified by searching the PubMed database using the keywords 'H1N1', 'pandemic', 'pandemics', 'shed' and 'shedding'. Any study of humans with an outcome measure of viral shedding was eligible for inclusion in the review. Comparisons by age, degree of severity and antiviral treatment were made with forest plots. The search returned 214 articles of which 22 were eligible for the review. Significant statistical heterogeneity between studies precluded meta-analysis. The mean duration of viral shedding generally increased with severity of clinical presentation, but we found no evidence of longer shedding duration of influenza A(H1N1)pdm09 among children compared with adults. Shorter viral shedding duration was observed when oseltamivir treatment was administered within 48 hours of illness onset. Considerable differences in the design and analysis of viral shedding studies limit their comparison and highlight the need for a standardised approach. These insights have implications not only for pandemic planning, but also for informing responses and study of seasonal influenza now that the A(H1N1)pdm09 virus has become established as the seasonal H1N1 influenza virus.

  15. PD-L1 Expression Induced by the 2009 Pandemic Influenza A(H1N1) Virus Impairs the Human T Cell Response

    Science.gov (United States)

    Arriaga-Pizano, Lourdes; Ferat-Osorio, Eduardo; Mora-Velandia, Luz María; Pastelin-Palacios, Rodolfo; Villasís-Keever, Miguel Ángel; Alpuche-Aranda, Celia; Sánchez-Torres, Luvia Enid; Isibasi, Armando; Bonifaz, Laura; López-Macías, Constantino

    2013-01-01

    PD-L1 expression plays a critical role in the impairment of T cell responses during chronic infections; however, the expression of PD-L1 on T cells during acute viral infections, particularly during the pandemic influenza virus (A(H1N1)pdm09), and its effects on the T cell response have not been widely explored. We found that A(H1N1)pdm09 virus induced PD-L1 expression on human dendritic cells (DCs) and T cells, as well as PD-1 expression on T cells. PD-L1 expression impaired the T cell response against A(H1N1)pdm09 by promoting CD8+ T cell death and reducing cytokine production. Furthermore, we found increased PD-L1 expression on DCs and T cells from influenza-infected patients from the first and second 2009 pandemic waves in Mexico City. PD-L1 expression on CD8+ T cells correlated inversely with T cell proportions in patients infected with A(H1N1)pdm09. Therefore, PD-L1 expression on DCs and T cells could be associated with an impaired T cell response during acute infection with A(H1N1)pdm09 virus. PMID:24187568

  16. Specific Recognition of Influenza A/H1N1/2009 Antibodies in Human Serum: A Simple Virus-Free ELISA Method

    Science.gov (United States)

    Alvarez, Mario M.; López-Pacheco, Felipe; Aguilar-Yañez, José M.; Portillo-Lara, Roberto; Mendoza-Ochoa, Gonzalo I.; García-Echauri, Sergio; Freiden, Pamela; Schultz-Cherry, Stacey; Zertuche-Guerra, Manuel I.; Bulnes-Abundis, David; Salgado-Gallegos, Johari; Elizondo-Montemayor, Leticia; Hernández-Torre, Martín

    2010-01-01

    Background Although it has been estimated that pandemic Influenza A H1N1/2009 has infected millions of people from April to October 2009, a more precise figure requires a worldwide large-scale diagnosis of the presence of Influenza A/H1N1/2009 antibodies within the population. Assays typically used to estimate antibody titers (hemagglutination inhibition and microneutralization) would require the use of the virus, which would seriously limit broad implementation. Methodology/Principal Findings An ELISA method to evaluate the presence and relative concentration of specific Influenza A/H1N1/2009 antibodies in human serum samples is presented. The method is based on the use of a histidine-tagged recombinant fragment of the globular region of the hemagglutinin (HA) of the Influenza A H1N1/2009 virus expressed in E. coli. Conclusions/Significance The ELISA method consistently discerns between Inf A H1N1 infected and non-infected subjects, particularly after the third week of infection/exposure. Since it does not require the use of viral particles, it can be easily and quickly implemented in any basic laboratory. In addition, in a scenario of insufficient vaccine availability, the use of this ELISA could be useful to determine if a person has some level of specific antibodies against the virus and presumably at least partial protection. PMID:20418957

  17. Specific recognition of influenza A/H1N1/2009 antibodies in human serum: a simple virus-free ELISA method.

    Directory of Open Access Journals (Sweden)

    Mario M Alvarez

    Full Text Available BACKGROUND: Although it has been estimated that pandemic Influenza A H1N1/2009 has infected millions of people from April to October 2009, a more precise figure requires a worldwide large-scale diagnosis of the presence of Influenza A/H1N1/2009 antibodies within the population. Assays typically used to estimate antibody titers (hemagglutination inhibition and microneutralization would require the use of the virus, which would seriously limit broad implementation. METHODOLOGY/PRINCIPAL FINDINGS: An ELISA method to evaluate the presence and relative concentration of specific Influenza A/H1N1/2009 antibodies in human serum samples is presented. The method is based on the use of a histidine-tagged recombinant fragment of the globular region of the hemagglutinin (HA of the Influenza A H1N1/2009 virus expressed in E. coli. CONCLUSIONS/SIGNIFICANCE: The ELISA method consistently discerns between Inf A H1N1 infected and non-infected subjects, particularly after the third week of infection/exposure. Since it does not require the use of viral particles, it can be easily and quickly implemented in any basic laboratory. In addition, in a scenario of insufficient vaccine availability, the use of this ELISA could be useful to determine if a person has some level of specific antibodies against the virus and presumably at least partial protection.

  18. A highly pathogenic avian influenza virus H5N1 with 2009 pandemic H1N1 internal genes demonstrated increased replication and transmission in pigs

    Science.gov (United States)

    This study investigated the pathogenicity and transmissibility of a reverse-genetics derived highly pathogenic avian influenza (HPAI) H5N1 influenza A virus (IAV), A/Iraq/775/06, and a reassortant virus comprised of the HA and NA from A/Iraq/775/06 and the internal genes of a 2009 pandemic H1N1, A/N...

  19. Molecular evolutionary analysis of pH1N1 2009 influenza virus in Reunion Island, South West Indian Ocean region: a cohort study.

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    Hervé Pascalis

    Full Text Available BACKGROUND/OBJECTIVES: Molecular epidemiology is a powerful tool to decipher the dynamics of viral transmission, quasispecies temporal evolution and origins. Little is known about the pH1N1 molecular dynamics in general population. A prospective study (CoPanFlu-RUN was carried out in Reunion Island to characterize pH1N1 genetic variability and molecular evolution occurring in population during the pH1N1 Influenza pandemic in 2009. METHODOLOGY: We directly amplified pH1N1 genomes from 28 different nasal swabs (26 individuals from 21 households. Fifteen strains were fully sequenced and 13 partially. This includes pairs of sequences from different members of 5 separate households; and two pairs from individuals, collected at different times. We assessed the molecular evolution of pH1N1 by genetic variability and phylogenetic analyses. PRINCIPAL FINDINGS: We found that i Reunion pH1N1 sequences stemmed from global "clade 7" but shaped two phylogenetic sub-clades; ii D239E mutation was identified in the hemagglutinin protein of all Reunion sequences, a mutation which has been associated elsewhere with mild-, upper-respiratory tract pH1N1 infecting strains; iii Date estimates from molecular phylogenies predicted clade emergence some time before the first detection of pH1N1 by the epidemiological surveillance system; iv Phylogenetic relatedness was observed between Reunion pH1N1 viruses and those from other countries in South-western Indian Ocean area; v Quasispecies populations were observed within households and individuals of the cohort-study. CONCLUSIONS: Surveillance and/or prevention systems presently based on Influenza virus sequence variation should take into account that the majority of studies of pH1N1 Influenza generate genetic data for the HA/NA viral segments obtained from hospitalized-patients, which is potentially non-representative of the overall viral diversity within whole populations. Our observations highlight the importance of

  20. Efficacy of soap and water and alcohol-based hand-rub preparations against live H1N1 influenza virus on the hands of human volunteers.

    Science.gov (United States)

    Grayson, M Lindsay; Melvani, Sharmila; Druce, Julian; Barr, Ian G; Ballard, Susan A; Johnson, Paul D R; Mastorakos, Tasoula; Birch, Christopher

    2009-02-01

    Although pandemic and avian influenza are known to be transmitted via human hands, there are minimal data regarding the effectiveness of routine hand hygiene (HH) protocols against pandemic and avian influenza. Twenty vaccinated, antibody-positive health care workers had their hands contaminated with 1 mL of 10(7) tissue culture infectious dose (TCID)(50)/0.1 mL live human influenza A virus (H1N1; A/New Caledonia/20/99) before undertaking 1 of 5 HH protocols (no HH [control], soap and water hand washing [SW], or use of 1 of 3 alcohol-based hand rubs [61.5% ethanol gel, 70% ethanol plus 0.5% chlorhexidine solution, or 70% isopropanol plus 0.5% chlorhexidine solution]). H1N1 concentrations were assessed before and after each intervention by viral culture and real-time reverse-transcriptase polymerase chain reaction (PCR). The natural viability of H1N1 on hands for >60 min without HH was also assessed. There was an immediate reduction in culture-detectable and PCR-detectable H1N1 after brief cutaneous air drying--14 of 20 health care workers had H1N1 detected by means of culture (mean reduction, 10(3-4) TCID(50)/0.1 mL), whereas 6 of 20 had no viable H1N1 recovered; all 20 health care workers had similar changes in PCR test results. Marked antiviral efficacy was noted for all 4 HH protocols, on the basis of culture results (14 of 14 had no culturable H1N1; (Peffective in reducing influenza A virus on human hands, although SW is the most effective intervention. Appropriate HH may be an important public health initiative to reduce pandemic and avian influenza transmission.

  1. Avian-like A (H1N1) swine influenza virus antibodies among swine farm residents and pigs in southern China.

    Science.gov (United States)

    Zhou, Han; Cao, Zhenpeng; Tan, Likai; Fu, Xinliang; Lu, Gang; Qi, Wenbao; Ke, Changwen; Wang, Heng; Sun, Lingshuang; Zhang, Guihong

    2014-01-01

    Infection of human with avian-like A (H1N1) swine influenza virus (SIV) occasionally occurs in China, suggesting a potential risk of cross-species transmission of the swine influenza H1N1 virus from pigs to humans, particularly to those having direct contact with pigs. A seroepidemiological study was conducted to assess the prevalence of antibodies against the avian-like A (H1N1) SIV among swine farm residents and pigs in southern China to evaluate the risk of infection to swine farm workers. Hemagglutination inhibition (HI) assays revealed that 11.17% (61/546) of the sera samples from swine farm residents in southern China were positive for antibodies against the avian-like A (H1N1) SIV. The difference in numbers of antibody-positive samples obtained from swine farm residents and a control group of healthy city residents was statistically significant (P = 0.031). In addition, 219 of the 1,180 serum samples from pigs were positive for the antibodies against an avian-like A (H1N1) SIV, A/swine/Guangdong/SS1/2013(H1N1), as assessed by HI. The data suggest that occupational exposure of swine farm residents and veterinarians in southern China to pigs may increase their risk of acquiring avian-like A (H1N1) SIV infection. According to a special pig farming model in southern China, the staff and residents are in close contact with infected pigs and may be among the first to become infected.

  2. Antiviral therapy and outcomes of patients with pneumonia caused by influenza A pandemic (H1N1 virus.

    Directory of Open Access Journals (Sweden)

    Shi-gui Yang

    Full Text Available BACKGROUND: There is limited data on the clinical outcome of patients with pandemic H1N1 (pH1N1 pneumonia who received oseltamivir treatment, especially when the treatment was administered more than 48 hours after symptom onset. METHODS: During the pandemic in 2009, a cohort of pH1N1 influenza pneumonia was built in China, and their clinical information was collected systematically, and analyzed with Cox models. RESULTS: 920 adults and 541 children with pneumonia who didn't receive corticosteroids were analyzed. In-hospital mortality was higher in adults who did not receive antiviral therapy (18.2% than those with who received oseltamivir ≤ 2 days (2.9%, between 2-5 days (4.6% and >5 days after illness onset (4.9%, p5 days, respectively. For males patients, aged ≥ 14 years and baseline PaO(2/FiO(23.8 mg/kg/d did not improve clinical outcome (mortality, higher dose 2.5% vs standard dose 2.8%, p>0.05. CONCLUSIONS: Antiviral therapy might reduce mortality of patients with pH1N1 pneumonia, even when initiated more than 48 hours after onset of illness. Greater protective effects might be in males, patients aged 14-60 years, and patients with PaO(2/FiO(2<200.

  3. The association between serum biomarkers and disease outcome in influenza A(H1N1)pdm09 virus infection

    DEFF Research Database (Denmark)

    Davey, Richard T; Lynfield, Ruth; Dwyer, Dominic E

    2013-01-01

    Prospective studies establishing the temporal relationship between the degree of inflammation and human influenza disease progression are scarce. To assess predictors of disease progression among patients with influenza A(H1N1)pdm09 infection, 25 inflammatory biomarkers measured at enrollment were...

  4. Analysis of characteristics of whole-genome of influenza A H1N1 virus in Qingdao between year 2009 and 2011

    Institute of Scientific and Technical Information of China (English)

    汪照国

    2014-01-01

    Objective To investigate characteristics of the whole-genome of influenza A H1N1 virus circulated in Qingdao from year 2009 to 2011.Methods RNA of 35influenza A H1N1 virus isolates circulated in Qingdao between year 2009 and 2011 was extracted and all segments were amplified by RT-PCR.The sequence was then detected and assembled by software Sequencher.25HA full-length sequences published on GenBank were selected as reference.While MEGA 5.0 software package was explored for

  5. 甲型H1N1流感死亡病例三株病毒分离株血凝素基因测序分析%Sequence analysis of the hemagglutinin gene of isolates viruses from 3 novel influenza A ( H1N1 )deaths

    Institute of Scientific and Technical Information of China (English)

    张如胜; 欧新华; 田斌

    2010-01-01

    Objective To understand the origin and variation of the hemagglutinin gene of isolates viruses from 3 novel influenza A( H1N1 ) deaths in Changsha ( A/Hunan Kaifu/SWL4142/2009 ( H1N1 ) , A/Hunan Changsha/SWL4346/2009 ( H1 N1 ) and A/Hunan Furong/SWL4224/2009( H1N1 )). Methods The nasopharyngeal swab specimens from the 3 novel influenza A( H1N1 ) deaths in Changsha were tested by RT-PCR and influenza viruses were isolated simultaneously. With the sequencing primers recommended by World Health Organization (WHO), the HA gene of sequences of 3 novel influenza A( H1N1 ) deaths were tested by CEQTM 8000 Genetic Analysis System, through dye terminator cycle sequencing. The sequencing results were submitted to GenBank, then the results were analyzed for amino acid alignment and phylogenetic tree analysis with ClustalX and Mega4.1 software. Results All the nucleotide homologies of HA gene sequences in A/Hunan Kaifu/SWL4142/2009 ( H1N1 ), A/Hunan Changsha/SWL4346/2009 ( H1N1 ) and A/Hunan Furong/SWL4224/2009( H1N1 ) are 99% as compared with the novel influenza A( H1N1 ) virus strains of A/NewYork/3502/2009 ( H1N1 ), A/Shanghai/71T/2009 ( H1N1 ) and A/Chita/01/2009 ( H1N1 )The nucleotide homology of the 3 HA gene sequences are more than 99. 5% the same compared with the novel influenza A( H1N1 ) virus strain ( A/Sichuan/1/2009( H1N1 ) ) in China. Phylogenetic tree analysis reveals that 2009 novel influenza A(H1N1 ) viruses including 3 HA gene sequences of A/Hunan Kaifu/SWL4142/2009 ( H1 N1 ), A/Hunan Changsha/SWL4346/2009 ( H1N1 ), A/Hunan Furong/SWL4224/2009( H1N1 ) had a close evolutionary relationship with the swine H1 virus isolates in North America ( A/Swine/Indiana/P12439/00), but a distant evolutionary relationship with those human seasonal A( H1 N1 ) influenza virus and avian. After comparing with genes of A/Swine/Indiana/P12439/00, we found that the HA gene sequences of the 3 viruses isolated had 28,30 and 27 amino acids with mutation respectively, but only one (R53

  6. Clinical differences between influenza A (H1N1 virus and respiratory infection between the two waves in 2009 and 2010

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    Zarogoulidis P

    2012-08-01

    Full Text Available Paul Zarogoulidis,1,2 Dimitrios Glaros,1 Ioannis Kioumis,2 Eirini Terzi,1 Konstantinos Porpodis,2 Anastasios Tsiotsios,2 Anastasios Kallianos,3 Georgia Trakada,4 Nikolaos Machairiotis,1 Aikaterini Stylianakil,1 Antonis Sakas,1 Ageliki Rapti,3 Nikolaos Courcoutsakis,5 Theodoros C Constantinidis,6 Efstartios Maltezos,1 Konstantinos Zarogoulidis21Unit of Infectious Diseases, General University Hospital of Alexandroupolis, Democritus University of Thrace, Komotini, 2Pulmonary Department, "G Papanikolaou" General Hospital, Aristotle University of Thessaloniki, Thessaloniki, 3Second Pulmonology Clinic, Hospital of Chest Diseases "Sotiria", Athens, 4Pulmonary Department, "Alexandra" General Hospital, University of Athens, Athens, 5Radiology Department, University General Hospital of Alexandroupolis, 6Laboratory of Hygiene and Environmental Protection, Occupational Medicine Section, Democritus University of Thrace, Komotini, GreeceBackground: The purpose of the present retrospective study was to examine the clinical differences between patients hospitalized with H1N1 virus and those hospitalized with nonvirus respiratory tract infection in 2009 and 2010.Methods: Adult patient data were collected from three tertiary hospital centers. Real-time reverse transcriptase polymerase chain reaction testing was used to confirm the diagnosis. We included 106 H1N1-positive patients (52 from 2009 and 54 from 2010. These data were compared with those from 108 patients with H1N1-negative respiratory tract infection (51 patients from 2009 and 57 from 2010.Results: In 2009, the mean age was 36.4 years for H1N1-positive patients versus 46.4 years for H1N1-negative patients, and mean body mass index (BMI was 26.4 kg/m2 patients and 28.1 kg/m2, respectively. In 2009, seven patients required intubation, six of whom were H1N1-positive. In 2010, the mean age was 43.8 years for H1N1-positive patients versus 60.2 years for H1N1-negative patients, and mean BMI was 32.3 kg/m2 and

  7. Prolonged period of acute bronchitis with late progression to acute respiratory distress syndrome as possible result of influenza A (H1N1) virus infection.

    Science.gov (United States)

    Homsi, Samer; Milojkovic, Natasa; Alawad, Bashar; Homsi, Yamen

    2012-09-01

    Young adults with underlying medical conditions who are infected with the H1N1 virus are at risk of quickly progressing from mild upper airways infection to severe ARDS within 4 to 5 days after the onset of the illness. Here, we report the case of a 46-year-old morbidly obese and diabetic woman infected with the H1N1 virus who developed acute bronchitis that lasted for 4 weeks and then progressed to ARDS. We discuss the month-long persistence of the H1N1 viral bronchitis and its late progression to ARDS which may reflect prolonged viral activity. Such a prolonged, rather than quick, course of deterioration can cause clinicians to misdiagnose the etiology of the ARDS and may cause the patient to receive a prolonged treatment with steroids to treat bronchitis symptoms. These steroids may cause increased viral replication and promote parenchymal involvement and the development of ARDS.

  8. 2009 pandemic influenza A (H1N1 virus outbreak and response--Rwanda, October, 2009-May, 2010.

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    Justin Wane

    Full Text Available BACKGROUND: In October 2009, the first case of pandemic influenza A(H1N1pdm09 (pH1N1 was confirmed in Kigali, Rwanda and countrywide dissemination occurred within several weeks. We describe clinical and epidemiological characteristics of this epidemic. METHODS: From October 2009 through May 2010, we undertook epidemiologic investigations and response to pH1N1. Respiratory specimens were collected from all patients meeting the WHO case definition for pH1N1, which were tested using CDC's real time RT-PCR protocol at the Rwandan National Reference Laboratory (NRL. Following documented viral transmission in the community, testing focused on clinically severe and high-risk group suspect cases. RESULTS: From October 9, 2009 through May 31, 2010, NRL tested 2,045 specimens. In total, 26% (n = 532 of specimens tested influenza positive; of these 96% (n = 510 were influenza A and 4% (n = 22 were influenza B. Of cases testing influenza A positive, 96.8% (n = 494, 3% (n = 15, and 0.2% (n = 1 were A(H1N1pdm09, Seasonal A(H3 and Seasonal A(non-subtyped, respectively. Among laboratory-confirmed cases, 263 (53.2% were children <15 years and 275 (52% were female. In total, 58 (12% cases were hospitalized with mean duration of hospitalization of 5 days (Range: 2-15 days. All cases recovered and there were no deaths. Overall, 339 (68% confirmed cases received oseltamivir in any setting. Among all positive cases, 26.9% (143/532 were among groups known to be at high risk of influenza-associated complications, including age <5 years 23% (122/532, asthma 0.8% (4/532, cardiac disease 1.5% (8/532, pregnancy 0.6% (3/532, diabetes mellitus 0.4% (2/532, and chronic malnutrition 0.8% (4/532. CONCLUSIONS: Rwanda experienced a PH1N1 outbreak which was epidemiologically similar to PH1N1 outbreaks in the region. Unlike seasonal influenza, children <15 years were the most affected by pH1N1. Lessons learned from the outbreak response included the need to

  9. Genetic diversity of influenza A(H1N1)2009 virus circulating during the season 2010-2011 in Spain.

    Science.gov (United States)

    Ledesma, Juan; Pozo, Francisco; Reina, Gabriel; Blasco, Miriam; Rodríguez, Guadalupe; Montes, Milagrosa; López-Miragaya, Isabel; Salvador, Carmen; Reina, Jordi; Ortíz de Lejarazu, Raúl; Egido, Pilar; López Barba, José; Delgado, Concepción; Cuevas, María Teresa; Casas, Inmaculada

    2012-01-01

    Genetic diversity of influenza A(H1N1)2009 viruses has been reported since the pandemic virus emerged in April 2009. Different genetic clades have been identified and defined based on amino acid substitutions found in the haemagglutinin (HA) protein sequences. In Spain, circulating influenza viruses are monitored each season by the regional laboratories enrolled in the Spanish Influenza Surveillance System (SISS). The analysis of the HA gene sequence helps to detect the genetic diversity and viral evolution. To perform an analysis of the genetic diversity of influenza A(H1N1)2009 viruses circulating in Spain during the season 2010-2011 based on analysis of the HA sequence gene. Phylogenetic analysis based on the HA1 subunit of the haemagglutinin gene was carried out on 220 influenza A(H1N1)2009 viruses circulating during the season 2010-2011. Six different genetic groups were identified among circulating A(H1N1)2009 viruses, five of them were previously reported during season 2010-2011. A new group, characterized by E172K and K308E changes and a proline at position 83, was observed in 12.27% of the Spanish viruses. Co-circulation of six different genetic groups of influenza A(H1N1)2009 viruses was identified in Spain during the season 2010-2011. Nevertheless, at this stage, none of the groups identified to date have resulted in significant antigenic changes according to data collected by World Health Organization Collaborating Centres for influenza surveillance. Copyright © 2011 Elsevier B.V. All rights reserved.

  10. Detection of the Pandemic H1N1/2009 Influenza A Virus by a Highly Sensitive Quantitative Real-time Reverse-transcription Polymerase Chain Reaction Assay

    Institute of Scientific and Technical Information of China (English)

    Zhu Yang; Guoliang Mao; Yujun Liu; Yuan-Chuan Chen; Chengjing Liu; Jun Luo; Xihan Li

    2013-01-01

    A quantitative real time reverse-transcription polymerase chain reaction (qRT-PCR) assay with specific primers recommended by the World Health Organization (WHO) has been widely used successfully for detection and monitoring of the pandemic H1N 1/2009 influenza A virus.In this study,we report the design and characterization of a novel set of primers to be used in a qRT-PCR assay for detecting the pandemic H1N1/2009 virus.The newly designed primers target three regions that are highly conserved among the hemagglutinin (HA) genes of the pandemic H1N1/2009 viruses and are different from those targeted by the WHO-recommended primers.The qRT-PCR assays with the newly designed primers are highly specific,and as specific as the WHO-recommended primers for detecting pandemic H1N1/2009 viruses and other influenza viruses including influenza B viruses and influenza A viruses of human,swine,and raccoon dog origin.Furthermore,the qRT-PCR assays with the newly designed primers appeared to be at least 10-fold more sensitive than those with the WHO-recommended primers as the detection limits of the assays with our primers and the WHO-recommended primers were 2.5 and 25 copies of target RNA per reaction,respectively.When tested with 83 clinical samples,32 were detected to be positive using the qRT-PCR assays with our designed primers,while only 25 were positive by the assays with the WHO-recommended primers.These results suggest that the qRT-PCR system with the newly designed primers represent a highly sensitive assay for diagnosis of the pandemic H1N1/2009 virus infection.

  11. Seasonal and pandemic influenza H1N1 viruses induce differential expression of SOCS-1 and RIG-I genes and cytokine/chemokine production in macrophages.

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    Ramírez-Martínez, Gustavo; Cruz-Lagunas, Alfredo; Jiménez-Alvarez, Luis; Espinosa, Enrique; Ortíz-Quintero, Blanca; Santos-Mendoza, Teresa; Herrera, María Teresa; Canché-Pool, Elsy; Mendoza, Criselda; Bañales, José L; García-Moreno, Sara A; Morán, Juan; Cabello, Carlos; Orozco, Lorena; Aguilar-Delfín, Irma; Hidalgo-Miranda, Alfredo; Romero, Sandra; Suratt, Benjamin T; Selman, Moisés; Zúñiga, Joaquín

    2013-04-01

    Infection with pandemic (pdm) A/H1N1 virus induces high levels of pro-inflammatory mediators in blood and lungs of experimental animals and humans. To compare the involvement of seasonal A/PR/8/34 and pdm A/H1N1 virus strains in the regulation of inflammatory responses, we analyzed the changes in the whole-genome expression induced by these strains in macrophages and A549 epithelial cells. We also focused on the functional implications (cytokine production) of the differential induction of suppressors of cytokine signaling (SOCS)-1, SOCS-3, retinoid-inducible gene (RIG)-I and interferon receptor 1 (IFNAR1) genes by these viral strains in early stages of the infection. We identified 130 genes differentially expressed by pdm A/H1N1 and A/PR/8/34 infections in macrophages. mRNA levels of SOCS-1 and RIG-I were up-regulated in macrophages infected with the A/PR/8/34 but not with pdm A/H1N1 virus. mRNA levels of SOCS-3 and IFNAR1 induced by A/PR/8/34 and pdm A/H1N1 strains in macrophages, as well as in A549 cells were similar. We found higher levels of IL-6, TNF-α, IL-10, CCL3, CCL5, CCL4 and CXCL8 (p < 0.05) in supernatants from cultures of macrophages infected with the pdm A/H1N1 virus compared to those infected with the A/PR/8/34 strain, coincident with the lack of SOCS-1 and RIG-I expression. In contrast, levels of INF-α were higher in cultures of macrophages 48h after infection with the A/PR/8/34 strain than with the pdm A/H1N1 virus. These findings suggest that factors inherent to the pdm A/H1N1 viral strain may increase the production of inflammatory mediators by inhibiting SOCS-1 and modifying the expression of antiviral immunity-related genes, including RIG-I, in human macrophages. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. Insights from investigating the interactions of adamantane-based drugs with the M2 proton channel from the H1N1 swine virus

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jing-Fang [College of Life Science and Biotechnology, Shanghai Jiaotong University, Shanghai 200240 (China); Wei, Dong-Qing, E-mail: dqwei@gordonlifescience.org [College of Life Science and Biotechnology, Shanghai Jiaotong University, Shanghai 200240 (China); Gordon Life Science Institute, 13784 Torrey Del Mar Drive, San Diego, CA 92130 (United States); Chou, Kuo-Chen [College of Life Science and Biotechnology, Shanghai Jiaotong University, Shanghai 200240 (China); Gordon Life Science Institute, 13784 Torrey Del Mar Drive, San Diego, CA 92130 (United States)

    2009-10-16

    The M2 proton channel is one of indispensable components for the influenza A virus that plays a vital role in its life cycle and hence is an important target for drug design against the virus. In view of this, the three-dimensional structure of the H1N1-M2 channel was developed based on the primary sequence taken from a patient recently infected by the H1N1 (swine flu) virus. With an explicit water-membrane environment, molecular docking studies were performed for amantadine and rimantadine, the two commercial drugs generally used to treat influenza A infection. It was found that their binding affinity to the H1N1-M2 channel is significantly lower than that to the H5N1-M2 channel, fully consistent with the recent report that the H1N1 swine virus was resistant to the two drugs. The findings and the relevant analysis reported here might provide useful structural insights for developing effective drugs against the new swine flu virus.

  13. Pandemic (H1N1) 2009 Influenza Virus Infection in A Survivor Who Has Recovered from Severe H7N9 Virus Infection, China

    Science.gov (United States)

    Chen, Shan-Hui; Wu, Meng-Na; Qian, Yan-Hua; Ma, Guang-Yuan; Wang, Guo-Lin; Yang, Yang; Zhao, Teng; Lu, Bing; Ma, Mai-Juan; Cao, Wu-Chun

    2016-01-01

    We firstly report a patient who presented with severe complications after infection with influenza A(H1N1) pdm2009, more than 1 year after recovery from severe H7N9 virus infections. The population of patients who recovered from severe H7N9 infections might be at a higher risk to suffer severe complications after seasonal influenza infections, and they should be included in the high-risk populations recommended to receive seasonal influenza vaccination. PMID:27757100

  14. Pandemic (H1N1 2009 Influenza Virus Infection in A Survivor who has recovered from severe H7N9 Virus Infection, China

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    Shan-Hui Chen

    2016-10-01

    Full Text Available We firstly report a patient who presented with severe complications after infection with influenza A(H1N1 pdm2009, more than one year after recovery from severe H7N9 virus infections. The population of patients who recovered from severe H7N9 infections might be at a higher risk to suffer severe complications after seasonal influenza infections, and they should be included in the high-risk populations recommended to receive seasonal influenza vaccination.

  15. Enfermedad respiratoria grave en terapia intensiva durante la pandemia por el virus de influenza A (H1N1) 2009 Severe respiratory disease in an intensive care unit during influenza A(H1N1)2009 pandemia

    OpenAIRE

    2010-01-01

    Se describen pacientes hospitalizados en una unidad de terapia intensiva por enfermedad respiratoria aguda grave con características de influenza durante los primeros meses de la pandemia por influenza A(H1N1) 2009 en la Argentina. Evaluamos datos clínicos, scores de gravedad, pruebas de laboratorio, microbiología y radiología torácica al ingreso, evolución y mortalidad hospitalaria, comparando pacientes con y sin confirmación de H1N1 por test de reacción de polimerasa en cadena, transcriptas...

  16. Decreased serologic response in vaccinated military recruits during 2011 correspond to genetic drift in concurrent circulating pandemic A/H1N1 viruses.

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    Dennis J Faix

    Full Text Available BACKGROUND: Population-based febrile respiratory illness surveillance conducted by the Department of Defense contributes to an estimate of vaccine effectiveness. Between January and March 2011, 64 cases of 2009 A/H1N1 (pH1N1, including one fatality, were confirmed in immunized recruits at Fort Jackson, South Carolina, suggesting insufficient efficacy for the pH1N1 component of the live attenuated influenza vaccine (LAIV. METHODOLOGY/PRINCIPAL FINDINGS: To test serologic protection, serum samples were collected at least 30 days post-vaccination from recruits at Fort Jackson (LAIV, Parris Island (LAIV and trivalent inactivated vaccine [TIV] at Cape May, New Jersey (TIV and responses measured against pre-vaccination sera. A subset of 78 LAIV and 64 TIV sera pairs from recruits who reported neither influenza vaccination in the prior year nor fever during training were tested by microneutralization (MN and hemagglutination inhibition (HI assays. MN results demonstrated that seroconversion in paired sera was greater in those who received TIV versus LAIV (74% and 37%. Additionally, the fold change associated with TIV vaccination was significantly different between circulating (2011 versus the vaccine strain (2009 of pH1N1 viruses (ANOVA p value = 0.0006. HI analyses revealed similar trends. Surface plasmon resonance (SPR analysis revealed that the quantity, IgG/IgM ratios, and affinity of anti-HA antibodies were significantly greater in TIV vaccinees. Finally, sequence analysis of the HA1 gene in concurrent circulating 2011 pH1N1 isolates from Fort Jackson exhibited modest amino acid divergence from the vaccine strain. CONCLUSIONS/SIGNIFICANCE: Among military recruits in 2011, serum antibody response differed by vaccine type (LAIV vs. TIV and pH1N1 virus year (2009 vs. 2011. We hypothesize that antigen drift in circulating pH1N1 viruses contributed to reduce vaccine effectiveness at Fort Jackson. Our findings have wider implications regarding

  17. Radiologic Review of an Outbreak of the Pandemic (H1N1) 2009 Virus Infection at a University Hospital in Seoul, Korea

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    Choi, Seung Hee; Kang, Eun Young; Kim, Yoon Kyung; Woo, Ok Hee; Yong, Hwan Seok; Oh, Yu Whan [Dept. of Radiology, Korea University Guro Hospital, Korea University College of Medicine, Seoul (Korea, Republic of); Kim, Jang Su [Dept. of Laboratory Medicine, Korea University Guro Hospital, Korea University College of Medicine, Seoul (Korea, Republic of)

    2011-04-15

    To assess the frequency of radiologic abnormalities and investigate the radiologic findings of patients with a pandemic (H1N1) 2009 virus infection at a University hospital in Seoul, Korea. In November 2009, 9,427 patients were tested for pandemic (H1N1) 2009 virus and 3,849 (41%) were positive. Among them, only 338 (9%) underwent chest radiographs and 13 (0.3%) received chest CT. Two radiologists retrospectively reviewed all the radiologic images. Among the 338 patients, 287 (85%) were normal and 51 (15%) showed abnormalities. The frequency of abnormalities was significantly higher in children (41/212=19%) than in adults (10/126=8%) (p = 0.005). Of them, 42 (82%) patients had airspace pneumonia, whereas the remaining patients showed a bronchopneumonia pattern. Unilateral (82%) involvement was more common than bilateral (18%) involvement. Among patients who received chest CT, 12 (92%) showed abnormalities, with bilateral (67%) and random (75%) involvement being more common. Ground-glass opacity (67%) and centrilobular nodules (58%) were the more common CT findings. Only a small number of patients were critically ill enough to undergo further radiologic evaluation as a result of pandemic (H1N1) 2009 virus infection, and most patients had normal chest radiographs. Unilateral airspace pneumonia was the most common abnormality in patients infected with pandemic (H1N1) 2009 virus.

  18. Clinical importance and impact on the households of oseltamivir-resistant seasonal A/H1N1 influenza virus in healthy children in Italy

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    Esposito Susanna

    2010-08-01

    Full Text Available Abstract A resistance of A/H1N1 influenza viruses to oseltamivir has recently emerged in a number of countries. However, the clinical and socioeconomic importance of this resistance has not been precisely defined. As children have the highest incidence of influenza infection and are at high risk of severe disease, the aim of this study was to evaluate the clinical importance and the impact on the households of oseltamivir-resistant seasonal A/H1N1 influenza virus in an otherwise healthy pediatric population. A total of 4,726 healthy children younger than 15 years with influenza-like illness were tested for influenza viruses by real-time polymerase chain reaction in the winters of 2007-2008 and 2008-2009 in Italy. The influenza A virus-positive samples underwent neuraminidase gene analysis using pyrosequencing to identify mutations H275Y and N294 S in A/H1N1, and E119V, R292K, and N294 S in A/H3N2. Among the A/H1N1 subtypes, the H275Y mutation was found in 2/126 samples taken in 2007-2008 (1.6% and in all 17 samples (100%; p

  19. Seroprevalence of Antibodies to Pandemic (H1N1 2009 Influenza Virus Among Hospital Staff in a Medical Center in Taiwan

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    Yu-Jiun Chan

    2010-02-01

    Conclusion: The SPR of antibodies against the pandemic (H1N1 2009 virus in the hospital staff was higher than that in the general population, reflecting a higher contact risk. Prevaccination surveillance of the immune status of different risk groups may help to prioritize which groups should be vaccinated first.

  20. Enfermedad respiratoria grave en terapia intensiva durante la pandemia por el virus de influenza A (H1N1 2009

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    José Aquino-Esperanza

    2010-10-01

    Full Text Available Se describen pacientes hospitalizados en una unidad de terapia intensiva por enfermedad respiratoria aguda grave con características de influenza durante los primeros meses de la pandemia por influenza A(H1N1 2009 en la Argentina. Evaluamos datos clínicos, scores de gravedad, pruebas de laboratorio, microbiología y radiología torácica al ingreso, evolución y mortalidad hospitalaria, comparando pacientes con y sin confirmación de H1N1 por test de reacción de polimerasa en cadena, transcriptasa reversa (RT-PCR. Entre junio y julio de 2009 se internaron 31 pacientes adultos con una mediana de edad de 54 años (percentilo 25-75: 33-66. Presentaron test positivo para H1N1, 17 pacientes. Tenían al menos una condición concurrente 16 pacientes. La expresión radiográfica más frecuente fue infiltrados intersticio-alveolares bilaterales en 20 casos; 5 tenían consolidación lobar unilateral. La coinfección bacteriana (aislamiento de bacterias o IgM positiva para infecciones bacterianas, se demostró en 21 pacientes. Requirieron ventilación mecánica 23 pacientes y 18 desarrollaron síndrome de distrés respiratorio agudo (SDRA. La linfopenia y elevación de creatinina-fosfoquinasa fue frecuente (83% y 65%, respectivamente. Los 6 pacientes que murieron (19% eran mayores de 75 años o tenían cáncer o inmunodepresión. El tratamiento antiviral temprano (≤ 48 horas se asoció a menor necesidad de ventilación mecánica (54% vs. 89%; p: 0.043. No hubo diferencia significativa en las variables analizadas entre el grupo H1N1 positivo y el negativo, lo que sugiere tener igual enfoque terapéutico frente a una epidemia. La infección por H1N1 determinó falla respiratoria aguda y SDRA. La mortalidad ocurrió en pacientes añosos o con co-morbilidades graves.

  1. Factors Associated with Death Due to 2009 Influenza A (H1N1) Virus Infection and Acute Respiratory Distress Syndrome in Beijing, 2009-2011

    Institute of Scientific and Technical Information of China (English)

    Jin-qian; Zhang; Li-cheng; Zhang; Na; Ren; Ming; Zhang; Li-min; Guo; Xing-wang; Li; Jun; Cheng

    2012-01-01

    Objective Patients with H1N1 virus infection were hospitalized and quarantined, and some of them developed into acute respiratory failure, and were transfered to the medical intensive care unit of Beijing Ditan Hospital, Capital Medical University in Beijing, China. Methods The clinical features and preliminary epidemiologic findings among 30 patients with confirmed H1N1 virus infection who developed into acute respiratory failure for ventilatory support were investigated. Results A total of 30 patients(37.43 ± 18.80 years old) with 2009 influenza A(H1N1) related acute respiratory distress syndrome(ARDS) received treatment with mechanical ventilation, 15 cases of whom were male and 17 cases died of ARDS. Fatal cases were significantly associated with an APACHE Ⅱ score(P = 0.016), but not with PaO 2 /FIO 2(P = 0.912) and chest radiograph(P = 0.333). The most common complication was acute renal failure(n = 9). Five patients received extracorporeal membrane oxygenation(ECMO), 3 of whom died and the others survived. The major causes of death were multiple organ dysfunction syndrome(MODS)(39%), intractable respiratory failure(27%) and sepsis(20%). Conclusions Most patients with respiratory failure due to influenza A(H1N1) virus infection were young, with a high mortality, particularly associated with APACHE Ⅱ score, secondary infection of lung or type 2 diabetes mellitus.

  2. Control of a Reassortant Pandemic 2009 H1N1 Influenza Virus Outbreak in an Intensive Swine Breeding Farm: Effect of Vaccination and Enhanced Farm Management Practices.

    Science.gov (United States)

    Mughini-Gras, Lapo; Beato, Maria Serena; Angeloni, Giorgia; Monne, Isabella; Buniolo, Filippo; Zuliani, Federica; Morini, Matteo; Castellan, Alberto; Bonfanti, Lebana; Marangon, Stefano

    2015-04-13

    Influenza A viruses in swine cause considerable economic losses and raise concerns about their zoonotic potential. The current paucity of thorough empirical assessments of influenza A virus infection levels in swine herds under different control interventions hinders our understanding of their effectiveness. Between 2012 and 2013, recurrent outbreaks of respiratory disease caused by a reassortant pandemic 2009 H1N1 (H1N1pdm) virus were registered in a swine breeding farm in North-East Italy, providing the opportunity to assess an outbreak response plan based on vaccination and enhanced farm management. All sows/gilts were vaccinated with a H1N1pdm-specific vaccine, biosecurity was enhanced, weaning cycles were lengthened, and cross-fostering of piglets was banned. All tested piglets had maternally-derived antibodies at 30 days of age and were detectable in 5.3% of ~90 day-old piglets. There was a significant reduction in H1N1pdm RT-PCR detections after the intervention. Although our study could not fully determine the extent to which the observed trends in seropositivity or RT-PCR positivity among piglets were due to the intervention or to the natural course of the disease in the herd, we provided suggestive evidence that the applied measures were useful in controlling the outbreak, even without an all-in/all-out system, while keeping farm productivity at full.

  3. Systems-level comparison of host responses induced by pandemic and seasonal influenza A H1N1 viruses in primary human type I-like alveolar epithelial cells in vitro

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    Guan Yi

    2010-10-01

    Full Text Available Abstract Background Pandemic influenza H1N1 (pdmH1N1 virus causes mild disease in humans but occasionally leads to severe complications and even death, especially in those who are pregnant or have underlying disease. Cytokine responses induced by pdmH1N1 viruses in vitro are comparable to other seasonal influenza viruses suggesting the cytokine dysregulation as seen in H5N1 infection is not a feature of the pdmH1N1 virus. However a comprehensive gene expression profile of pdmH1N1 in relevant primary human cells in vitro has not been reported. Type I alveolar epithelial cells are a key target cell in pdmH1N1 pneumonia. Methods We carried out a comprehensive gene expression profiling using the Affymetrix microarray platform to compare the transcriptomes of primary human alveolar type I-like alveolar epithelial cells infected with pdmH1N1 or seasonal H1N1 virus. Results Overall, we found that most of the genes that induced by the pdmH1N1 were similarly regulated in response to seasonal H1N1 infection with respect to both trend and extent of gene expression. These commonly responsive genes were largely related to the interferon (IFN response. Expression of the type III IFN IL29 was more prominent than the type I IFN IFNβ and a similar pattern of expression of both IFN genes was seen in pdmH1N1 and seasonal H1N1 infection. Genes that were significantly down-regulated in response to seasonal H1N1 but not in response to pdmH1N1 included the zinc finger proteins and small nucleolar RNAs. Gene Ontology (GO and pathway over-representation analysis suggested that these genes were associated with DNA binding and transcription/translation related functions. Conclusions Both seasonal H1N1 and pdmH1N1 trigger similar host responses including IFN-based antiviral responses and cytokine responses. Unlike the avian H5N1 virus, pdmH1N1 virus does not have an intrinsic capacity for cytokine dysregulation. The differences between pdmH1N1 and seasonal H1N1 viruses

  4. Immunization of pigs with an attenuated pseudorabies virus recombinant expressing the haemagglutinin of pandemic swine origin H1N1 influenza A virus.

    Science.gov (United States)

    Klingbeil, Katharina; Lange, Elke; Teifke, Jens P; Mettenleiter, Thomas C; Fuchs, Walter

    2014-04-01

    Pigs can be severely harmed by influenza, and represent important reservoir hosts, in which new human pathogens such as the recent pandemic swine-origin H1N1 influenza A virus can arise by mutation and reassortment of genome segments. To obtain novel, safe influenza vaccines for pigs, and to investigate the antigen-specific immune response, we modified an established live-virus vaccine against Aujeszky's disease of swine, pseudorabies virus (PrV) strain Bartha (PrV-Ba), to serve as vector for the expression of haemagglutinin (HA) of swine-origin H1N1 virus. To facilitate transgene insertion, the genome of PrV-Ba was cloned as a bacterial artificial chromosome. HA expression occurred under control of the human or murine cytomegalovirus immediate early promoters (P-HCMV, P-MCMV), but could be substantially enhanced by synthetic introns and adaptation of the codon usage to that of PrV. However, despite abundant expression, the heterologous glycoprotein was not detectably incorporated into mature PrV particles. Replication of HA-expressing PrV in cell culture was only slightly affected compared to that of the parental virus strain. A single immunization of pigs with the PrV vector expressing the codon-optimized HA gene under control of P-MCMV induced high levels of HA-specific antibodies. The vaccinated animals were protected from clinical signs after challenge with a related swine-origin H1N1 influenza A virus, and challenge virus shedding was significantly reduced.

  5. Protection of pigs against pandemic swine origin H1N1 influenza A virus infection by hemagglutinin- or neuraminidase-expressing attenuated pseudorabies virus recombinants.

    Science.gov (United States)

    Klingbeil, Katharina; Lange, Elke; Blohm, Ulrike; Teifke, Jens P; Mettenleiter, Thomas C; Fuchs, Walter

    2015-03-01

    Influenza is an important respiratory disease of pigs, and may lead to novel human pathogens like the 2009 pandemic H1N1 swine-origin influenza virus (SoIV). Therefore, improved influenza vaccines for pigs are required. Recently, we demonstrated that single intranasal immunization with a hemagglutinin (HA)-expressing pseudorabies virus recombinant of vaccine strain Bartha (PrV-Ba) protected pigs from H1N1 SoIV challenge (Klingbeil et al., 2014). Now we investigated enhancement of efficacy by prime-boost vaccination and/or intramuscular administration. Furthermore, a novel PrV-Ba recombinant expressing codon-optimized N1 neuraminidase (NA) was included. In vitro replication of this virus was only slightly affected compared to parental virus. Unlike HA, the abundantly expressed NA was efficiently incorporated into PrV particles. Immunization of pigs with the two PrV recombinants, either singly or in combination, induced B cell proliferation and the expected SoIV-specific antibodies, whose titers increased substantially after boost vaccination. After immunization of animals with either PrV recombinant H1N1 SoIV challenge virus replication was significantly reduced compared to PrV-Ba vaccinated or naïve controls. Protective efficacy of HA-expressing PrV was higher than of NA-expressing PrV, and not significantly enhanced by combination. Despite higher serum antibody titers obtained after intramuscular immunization, transmission of challenge virus to naïve contact animals was only prevented after intranasal prime-boost vaccination with HA-expressing PrV-Ba.

  6. Design and performance of the CDC real-time reverse transcriptase PCR swine flu panel for detection of 2009 A (H1N1) pandemic influenza virus.

    Science.gov (United States)

    Shu, Bo; Wu, Kai-Hui; Emery, Shannon; Villanueva, Julie; Johnson, Roy; Guthrie, Erica; Berman, LaShondra; Warnes, Christine; Barnes, Nathelia; Klimov, Alexander; Lindstrom, Stephen

    2011-07-01

    Swine influenza viruses (SIV) have been shown to sporadically infect humans and are infrequently identified by the Influenza Division of the Centers for Disease Control and Prevention (CDC) after being received as unsubtypeable influenza A virus samples. Real-time reverse transcriptase PCR (rRT-PCR) procedures for detection and characterization of North American lineage (N. Am) SIV were developed and implemented at CDC for rapid identification of specimens from cases of suspected infections with SIV. These procedures were utilized in April 2009 for detection of human cases of 2009 A (H1N1) pandemic (pdm) influenza virus infection. Based on genetic sequence data derived from the first two viruses investigated, the previously developed rRT-PCR procedures were optimized to create the CDC rRT-PCR Swine Flu Panel for detection of the 2009 A (H1N1) pdm influenza virus. The analytical sensitivity of the CDC rRT-PCR Swine Flu Panel was shown to be 5 copies of RNA per reaction and 10(-1.3 - -0.7) 50% infectious doses (ID(50)) per reaction for cultured viruses. Cross-reactivity was not observed when testing human clinical specimens or cultured viruses that were positive for human seasonal A (H1N1, H3N2) and B influenza viruses. The CDC rRT-PCR Swine Flu Panel was distributed to public health laboratories in the United States and internationally from April 2009 until June 2010. The CDC rRT-PCR Swine Flu Panel served as an effective tool for timely and specific detection of 2009 A (H1N1) pdm influenza viruses and facilitated subsequent public health response implementation.

  7. Whole genome characterization of human influenza A(H1N1)pdm09 viruses isolated from Kenya during the 2009 pandemic.

    Science.gov (United States)

    Gachara, George; Symekher, Samuel; Otieno, Michael; Magana, Japheth; Opot, Benjamin; Bulimo, Wallace

    2016-06-01

    An influenza pandemic caused by a novel influenza virus A(H1N1)pdm09 spread worldwide in 2009 and is estimated to have caused between 151,700 and 575,400 deaths globally. While whole genome data on new virus enables a deeper insight in the pathogenesis, epidemiology, and drug sensitivities of the circulating viruses, there are relatively limited complete genetic sequences available for this virus from African countries. We describe herein the full genome analysis of influenza A(H1N1)pdm09 viruses isolated in Kenya between June 2009 and August 2010. A total of 40 influenza A(H1N1)pdm09 viruses isolated during the pandemic were selected. The segments from each isolate were amplified and directly sequenced. The resulting sequences of individual gene segments were concatenated and used for subsequent analysis. These were used to infer phylogenetic relationships and also to reconstruct the time of most recent ancestor, time of introduction into the country, rates of substitution and to estimate a time-resolved phylogeny. The Kenyan complete genome sequences clustered with globally distributed clade 2 and clade 7 sequences but local clade 2 viruses did not circulate beyond the introductory foci while clade 7 viruses disseminated country wide. The time of the most recent common ancestor was estimated between April and June 2009, and distinct clusters circulated during the pandemic. The complete genome had an estimated rate of nucleotide substitution of 4.9×10(-3) substitutions/site/year and greater diversity in surface expressed proteins was observed. We show that two clades of influenza A(H1N1)pdm09 virus were introduced into Kenya from the UK and the pandemic was sustained as a result of importations. Several closely related but distinct clusters co-circulated locally during the peak pandemic phase but only one cluster dominated in the late phase of the pandemic suggesting that it possessed greater adaptability.

  8. The impact of antigenic drift of influenza A virus on human herd immunity: Sero-epidemiological study of H1N1 in healthy Thai population in 2009.

    Science.gov (United States)

    Kanai, Yuta; Boonsathorn, Naphatsawan; Chittaganpitch, Malinee; Bai, Guirong; Li, Yonggang; Kase, Tetsuo; Takahashi, Kazuo; Okuno, Yoshinobu; Jampangern, Wipawee; Ikuta, Kazuyoshi; Sawanpanyalert, Pathom

    2010-07-26

    To examine the effect of the antigenic drift of H1N1 influenza viruses on herd immunity, neutralization antibodies from 744 sera from Thai healthy volunteers in 2008-2009, who had not been vaccinated for at least the last 5 years, were investigated by microneutralization (MN) and hemagglutination inhibition (HI) assays. Significantly higher MN titers were observed for the H1N1 Thai isolate in 2006 than in 2008. The results indicate that the antigenically drifted virus effectively escaped herd immunity. Since the low neutralization activity of herd immunity against drifted viruses is an important factor for viruses to spread efficiently, continuous sero-epidemiological study is required for public health.

  9. Genetic diversity of the haemagglutinin (HA) of human influenza a (H1N1) virus in montenegro: Focus on its origin and evolution.

    Science.gov (United States)

    Mugosa, Boban; Vujosevic, Danijela; Ciccozzi, Massimo; Valli, Maria Beatrice; Capobianchi, Maria Rosaria; Lo Presti, Alessandra; Cella, Eleonora; Giovanetti, Marta; Lai, Alessia; Angeletti, Silvia; Scarpa, Fabio; Terzić, Dragica; Vratnica, Zoran

    2016-11-01

    In 2009 an influenza A epidemic caused by a swine origin H1N1strain, unusual in human hosts, has been described. The present research is aimed to perform the first phylogenetic investigation on the influenza virus A (H1N1) strains circulating in Montenegro, from December 1, 2009, when the first case of death due to H1N1 was confirmed, and the epidemic began causing a total of four fatalities. The phylogenetic analysis of the strains circulating showed the absence of a pure Montenegrin cluster, suggesting the occurrence of multiple re-introductions in that population from different areas till as far as the early 2010. The time to most recent common ancestor (TMRCA) for the complete dataset has been dated in early 2008, pre-dating the first Montenegrin identification of H1N1 infection. These data suggest that virus was spreading undetected, may be as a consequence of unidentified infections in returning travelers. Anyhow, the estimated TMRCA of Montenegrin strains is fully consistent to that found in different areas. Compatibly with the time coverage of the study period here analyzed, molecular dynamic of Montenegrin strains follows similar trend as in other countries. J. Med. Virol. 88:1905-1913, 2016. © 2016 Wiley Periodicals, Inc.

  10. Viral shedding duration of pandemic influenza A H1N1 virus during an elementary school outbreak--Pennsylvania, May-June 2009.

    Science.gov (United States)

    Bhattarai, Achuyt; Villanueva, Julie; Palekar, Rakhee S; Fagan, Ryan; Sessions, Wendy; Winter, Jörn; Berman, Lashondra; Lute, James; Leap, Rebecca; Marchbanks, Tiffany; Sodha, Samir V; Moll, Mària; Xu, Xiyan; Fry, Alicia; Fiore, Anthony; Ostroff, Stephen; Swerdlow, David L

    2011-01-01

    We report shedding duration of 2009 pandemic influenza A (pH1N1) virus from a school-associated outbreak in Pennsylvania during May through June 2009. Outbreak-associated students or household contacts with influenza-like illness (ILI) onset within 7 days of interview were recruited. Nasopharyngeal specimens, collected every 48 hours until 2 consecutive nonpositive tests, underwent real-time reverse transcriptase polymerase chain reaction (rRT-PCR) and culture for pH1N1 virus. Culture-positive specimens underwent virus titrations. Twenty-six (median age, 8 years) rRT-PCR-positive persons, for pH1N1 virus, were included in analysis. Median shedding duration from fever onset by rRT-PCR was 6 days (range, 1-13) and 5 days (range, 1-7) by culture. Following fever resolution virus was isolated for a median of 2 days (range, 0-5). Highest and lowest virus titers detected, 2 and 5 days following fever onset, were 3.2 and 1.2 log(10) TCID(50)/mL respectively. Overall, shedding duration in children and adults were similar to seasonal influenza viruses.

  11. Influenza A(H1N1pdm09 virus suppresses RIG-I initiated innate antiviral responses in the human lung.

    Directory of Open Access Journals (Sweden)

    Wenxin Wu

    Full Text Available Influenza infection is a major cause of morbidity and mortality. Retinoic acid-inducible gene I (RIG-I is believed to play an important role in the recognition of, and response to, influenza virus and other RNA viruses. Our study focuses on the hypothesis that pandemic H1N1/09 influenza virus alters the influenza-induced proinflammatory response and suppresses host antiviral activity. We first compared the innate response to a clinical isolate of influenza A(H1N1pdm09 virus, OK/09, a clinical isolate of seasonal H3N2 virus, OK/06, and to a laboratory adapted seasonal H1N1 virus, PR8, using a unique human lung organ culture model. Exposure of human lung tissue to either pandemic or seasonal influenza virus resulted in infection and replication in alveolar epithelial cells. Pandemic virus induces a diminished RIG-I mRNA and antiviral cytokine response than seasonal virus in human lung. The suppression of antiviral response and RIG-I mRNA expression was confirmed at the protein level by ELISA and western blot. We performed a time course of RIG-I and interferon-β (IFN-β mRNA induction by the two viruses. RIG-I and IFN-β induction by OK/09 was of lower amplitude and shorter duration than that caused by PR8. In contrast, the pandemic virus OK/09 caused similar induction of proinflammatory cytokines, IL-8 and IL-6, at both the transcriptional and translational level as PR8 in human lung. Differential antiviral responses did not appear to be due to a difference in cellular infectivity as immunohistochemistry showed that both viruses infected alveolar macrophages and epithelial cells. These findings show that influenza A(H1N1pdm09 virus suppresses anti-viral immune responses in infected human lung through inhibition of viral-mediated induction of the pattern recognition receptor, RIG-I, though proinflammatory cytokine induction was unaltered. This immunosuppression of the host antiviral response by pandemic virus may have contributed to the more

  12. 568份疑似甲型H1N1流感病例标本病原学检测结果分析%Results of detection of 568 suspected influenza A virus subtype H1N1 patients

    Institute of Scientific and Technical Information of China (English)

    黄丽华; 唐保晖

    2011-01-01

    Aim To detect influenza A virus subtype H1N1 in Hechi City from suspected patients by nucleic acid assay. Methods The nucleic acids of influenza A and B viruses and nfluenza A virus subtype H1N1 were simultaneously detected from 568 suspected influenza A virus subtype H1N1 patients by using real time quantitative RT-PCR method (Real-time RT-PCR). Seasonal influenza virus subtype H1N1 and H3N2 would detected from the samples positive forinfluenza A virus nucleic acid,while negative for influenza B virus and influenza A virus subtype H1N1 nucleic acid.Results In the 568 suspected samples,there were 334 samples positive for influenza A H1N1 influenza virus nucleic acid and 14 positive for seasonal influenza virus subtype H1N1 nucleic acid positive,25 positive for seasonal influenza virus subtype H3N2 nucleic acid positive and 40 positive for no-differentiated influenza A virus nucleic acid. Conclusion Laboratory tests provide a basis for sensitive, specific and efficient confirmation and control of influenza A(H1N1 ).%目的 对河池市568份疑似甲型H1N1流感病例标本进行核酸检测,为甲型H1N1流感疫情的防控提供依据.方法 对疑似甲型H1N1流感病例标本用实时荧光定量RT-PCR法(Real-time RT-PCR)检测,检测项目为A型流感病毒核酸、B型流感病毒核酸和甲型H1N1流感病毒核酸,对A型流感病毒核酸阳性而B型流感病毒核酸和甲型H1N1流感病毒核酸均阴性标本再进行季节性流感病毒H1N1、H3N2亚型流感病毒核酸检测.结果 检测疑似病例标本568份,其中甲型H1N1流感病毒核酸阳性334份,季节性流感病毒H1N1亚型核酸阳性14份,季节性流感病毒H3N2亚型核酸阳性25份,A未分型流感病毒核酸阳性40份.结论 实验室检测为甲型H1N1流感疫情的确认、防控以及病人的处理提供了依据,对提高实验窒检测技术的敏感性、特异性和实效性具有重要的意义.

  13. Influenza H5N1 and H1N1 virus replication and innate immune responses in bronchial epithelial cells are influenced by the state of differentiation.

    Directory of Open Access Journals (Sweden)

    Renee W Y Chan

    Full Text Available Influenza H5N1 virus continues to be enzootic in poultry and transmits zoonotically to humans. Although a swine-origin H1N1 virus has emerged to become pandemic, its virulence for humans remains modest in comparison to that seen in zoonotic H5N1 disease. As human respiratory epithelium is the primary target cells for influenza viruses, elucidating the viral tropism and host innate immune responses of influenza H5N1 virus in human bronchial epithelium may help to understand the pathogenesis. Here we established primary culture of undifferentiated and well differentiated normal human bronchial epithelial (NHBE cells and infected with highly pathogenic influenza H5N1 virus (A/Vietnam/3046/2004 and a seasonal influenza H1N1 virus (A/Hong Kong/54/1998, the viral replication kinetics and cytokine and chemokine responses were compared by qPCR and ELISA. We found that the in vitro culture of the well differentiated NHBE cells acquired the physiological properties of normal human bronchi tissue which express high level of alpha2-6-linked sialic acid receptors and human airway trypsin-like (HAT protease, in contrast to the low expression in the non-differentiated NHBE cells. When compared to H1N1 virus, the H5N1 virus replicated more efficiently and induced a stronger type I interferon response in the undifferentiated NHBE cells. In contrast, in well differentiated cultures, H5N1 virus replication was less efficient and elicited a lower interferon-beta response in comparison with H1N1 virus. Our data suggest that the differentiation of bronchial epithelial cells has a major influence in cells' permissiveness to human H1N1 and avian H5N1 viruses and the host innate immune responses. The reduced virus replication efficiency partially accounts for the lower interferon-beta responses in influenza H5N1 virus infected well differentiated NHBE cells. Since influenza infection in the bronchial epithelium will lead to tissue damage and associate with the

  14. Recombination analysis and homology alignment of full-length genome sequences of die novel A/H1N1 influenza virus in 2009%2009年新型甲型H1N1流感病毒全基因组序列重组分析及同源性比对

    Institute of Scientific and Technical Information of China (English)

    鹿文英; 殷建华; 李淑华; 韩磊; 韩一芳; 苏彤; 曹广文

    2009-01-01

    Objective To analyze the genetic variation and recombination of the novel A/H1N1 influenza pandemic virus in 2009. Methods Full-length sequence of typical novel A/H1N1 influenza virus was downloaded from NCBI database. MEGA4.0 software was used to connect and align the eight fragments of the virus. Then the fragments of different subtypes such as H1N1, H5N1 and H3N2 of the historical strains from different hosts, including human, poultry and pigs, were connected and aligned in the same way. A phylogenetic tree was constructed by NJ method. The recombination analysis of 2009 pandemic virus was made with Simplot 3. 5.1 software. Results There was no clear variation (identity was 99.69% - 99. 93%) in the novel A/H1N1 influenza virus from April to September, 2009. Simplot and MEGA analysis indicated that the PB2, PB1, PA, HA, NP and NS of the novel A/H1N1 virus might originally evolve from the swine and human H1N1 virus isolated in North America (identity was 95. 25%, 95.08%, 95.21%, 93.52%, 95.23% and 94.78%, respectively). NA and MP showed high homology with the European swine H1N1 virus, the identity was 90.21% and 94.43%, respectively. Full-length sequence of the novel A/H1N1 influenza virus had a highest similarity with swine H1N1 virus isolated from North America (identity was 92.22%). Conclusions The novel A/H1N1 influenza pandemic virus in 2009 was originated from the reassortment and evolution of swine H1N1 2005 pandemic virus in North America, and the NA and MP fragments of European swine H1N1. There is no clear variation in novel influenza virus up to now. The novel A/H1N1 influenza vaccine possesses protective effect.%目的 分析2009年新型甲型H1N1流感爆发以来流感病毒的全基因组进化变异及重组情况.方法 从NCBI基因数据库下载2009年新型甲型H1N1流感病毒(A/H1N1)代表性全基因组序列,先用MEGA4.0软件对8个基因序列片段进行比对和拼接;然后将历史上流行的H1N1、H5N1、H3N2等不同宿

  15. Acetylsalicylic Acid (aspirin) in Vitro Inhibition of Influenza Virus H1N1%乙酰水杨酸(阿司匹林)体外对流感病毒H1N1的抑制作用

    Institute of Scientific and Technical Information of China (English)

    丁宁; 卢芯; 郑丛龙; 韦淳巍; 许梦亭; 向敏; 林雨馨

    2014-01-01

    探讨乙酰水杨酸(Acetylsalicylic Acid)在体外对流感病毒H1N1的抑制作用。采用血球凝集试验、神经氨酸酶活性抑制试验和鸡胚接种法,观察AS对流感病毒H1N1的抑制作用。血球凝集试验可以看出,AS对流感病毒H1N1包膜表面的血凝素活性有一定的抑制作用,且作用较为显著;鸡胚培养法的结果显示,AS明显抑制了流感病毒H1N1在鸡胚内的增值,实验组血凝效价低于1:2,对照组血凝效价为1:512;神经氨酸酶活性抑制试验的结果显示,AS能够明显抑制流感病毒H1N1的神经氨酸酶活性。结果表明AS在体外对流感病毒H1N1有明显的抑制作用,其抑制机理可能与AS对流感病毒血凝素和神经氨酸酶活性抑制有关。%To study the acetylsalicylic acid (AS) in vitro inhibition of influenza virus H1N1. Using methods of hemagglutination test, neuraminidase enzyme inhibition test and chicken embryo inoculation, the inhibition of influenza virus H1N1 was observed. Hemagglutination test results showed that AS inhibited activity of the H1N1 influenza virus hemagglutinin and the effect is more significant; embryo culture results showed, AS significantly inhibited H1N1 influenza virus in eggs value within the experimental group hemagglutination titer less than 1:2, the control group hemagglutination titer 1:512;neuraminidase enzyme inhibition test results showed, AS can inhibit the influenza virus H1N1 neuraminidase activity. All study showed that H1N1 influenza virus in vitro was significantly inhibited by AS, the mechanism is concern with AS inhibition of influenza virus hemagglutinin and neuraminidase inhibition of enzyme activity.

  16. Construction and Immunogenicity Evaluation of Recombinant Influenza A Viruses Containing Chimeric Hemagglutinin Genes Derived from Genetically Divergent Influenza A H1N1 Subtype Viruses.

    Science.gov (United States)

    McCormick, Kara; Jiang, Zhiyong; Zhu, Longchao; Lawson, Steven R; Langenhorst, Robert; Ransburgh, Russell; Brunick, Colin; Tracy, Miranda C; Hurtig, Heather R; Mabee, Leah M; Mingo, Mark; Li, Yanhua; Webby, Richard J; Huber, Victor C; Fang, Ying

    2015-01-01

    Influenza A viruses cause highly contagious diseases in a variety of hosts, including humans and pigs. To develop a vaccine that can be broadly effective against genetically divergent strains of the virus, in this study we employed molecular breeding (DNA shuffling) technology to create a panel of chimeric HA genes. Each chimeric HA gene contained genetic elements from parental swine influenza A viruses that had a history of zoonotic transmission, and also from a 2009 pandemic virus. Each parental virus represents a major phylogenetic clade of influenza A H1N1 viruses. Nine shuffled HA constructs were initially screened for immunogenicity in mice by DNA immunization, and one chimeric HA (HA-129) was expressed on both a A/Puerto Rico/8/34 backbone with mutations associated with a live, attenuated phenotype (PR8LAIV-129) and a A/swine/Texas/4199-2/98 backbone (TX98-129). When delivered to mice, the PR8LAIV-129 induced antibodies against all four parental viruses, which was similar to the breadth of immunity observed when HA-129 was delivered as a DNA vaccine. This chimeric HA was then tested as a candidate vaccine in a nursery pig model, using inactivated TX98-129 virus as the backbone. The results demonstrate that pigs immunized with HA-129 developed antibodies against all four parental viruses, as well as additional primary swine H1N1 influenza virus field isolates. This study established a platform for creating novel genes of influenza viruses using a molecular breeding approach, which will have important applications toward future development of broadly protective influenza virus vaccines.

  17. A polyvalent influenza A DNA vaccine induces heterologous immunity and protects pigs against pandemic A(H1N1)pdm09 virus infection

    DEFF Research Database (Denmark)

    Bragstad, Karoline; Vinner, Lasse; Hansen, Mette Sif

    2013-01-01

    intradermally with a combination of influenza DNA vaccine components based on the pandemic 1918 H1N1 (M and NP genes), pandemic 2009 H1N1pdm09 (HA and NA genes) and seasonal 2005 H3N2 genes (HA and NA genes) and investigated the protection against infection with virus both homologous and heterologous to the DNA......The composition of current influenza protein vaccines has to be reconsidered every season to match the circulating influenza viruses, continuously changing antigenicity. Thus, influenza vaccines inducing a broad cross-reactive immune response would be a great advantage for protection against both...... seasonal and emerging influenza viruses. We have developed an alternative influenza vaccine based on DNA expressing selected influenza proteins of pandemic and seasonal origin. In the current study, we investigated the protection of a polyvalent influenza DNA vaccine approach in pigs. We immunised pigs...

  18. Simultaneous infection of pigs and people with triple-reassortant swine influenza virus H1N1 at a U.S. county fair.

    Science.gov (United States)

    Killian, M L; Swenson, S L; Vincent, A L; Landgraf, J G; Shu, B; Lindstrom, S; Xu, X; Klimov, A; Zhang, Y; Bowman, A S

    2013-05-01

    Influenza-like illness was noted in people and pigs in attendance at an Ohio county fair in August 2007. The morbidity rate in swine approached 100% within 1-2 days of initial clinical signs being recognized, and approximately two dozen people developed influenza-like illness. Triple-reassortant swine H1N1 influenza viruses were identified in both pigs and people at the fair. The identified viruses (A/Sw/OH/511445/2007, A/Ohio/01/2007, and A/Ohio/02/2007) were similar to H1N1 swine influenza viruses currently found in the U.S. swine population. This case illustrates the possibility of transmission of swine influenza in settings where there is close human/swine interaction.

  19. Acceptance of a Vaccine Against Novel Influenza A (H1N1) Virus Among Health Care Workers in Two Major Cities in Mexico

    Science.gov (United States)

    Esteves-Jaramillo, Alejandra; Omer, Saad B.; Gonzalez-Diaz, Esteban; Salmon, Daniel A.; Hixson, Brooke; Navarro, Francisco; Kawa–Karasik, Simon; Frew, Paula; Morfin-Otero, Rayo; Noriega, Eduardo Rodriguez; Ramirez, Ylean; Rosas, Araceli; Acosta, Edgar; Badillo, Vianey Varela; Rio, Carlos Del

    2010-01-01

    Background and Aims Further cases of novel influenza A (H1N1) outbreak are expected in the coming months. Vaccination has been proven to be essential to control a pandemic of influenza; therefore, considerable efforts and resources have been devoted to develop a vaccine against the influenza A (H1N1) virus. With the current availability of the vaccine, it will be important to immunize as many people as possible. However, previous data with seasonal influenza vaccines have shown that there are multiple barriers related to perceptions and attitudes of the population that influence vaccine use. The aim of the study was to evaluate the acceptance of a newly developed vaccine against pandemic (H1N1) 2009 influenza A among healthcare workers (HCW) in Mexico. Methods We conducted a cross-sectional study among HCW in three hospitals in the two largest cities in Mexico—Mexico City and Guadalajara—between June and September 2009. Results A total of 1097 HCW participated in the survey. Overall, 80% (n = 880) intended to accept the H1N1 pandemic vaccine and 71.6% (n = 786) reported they would recommend the vaccine to their patients. Doctors were more likely to accept and recommend the vaccine than nurses. HCWs who intend to be immunized will be more likely to do so if they know that the vaccine is safe and effective. Conclusions Knowledge of the willingness to accept the vaccine can be used to plan strategies that will effectively respond to the needs of the population studied, reducing the health and economic impact of novel influenza A (H1N1) virus. PMID:20304260

  20. [Analysis of HA and NA Genes of Influenza A H1N1 Virus in Yunnan Province during 2009-2014].

    Science.gov (United States)

    Li, Juan; Zhao, Xiaonan; Cao, Yihui; Ning, Deming; Fu, Xiaoqing; Xu, Wen

    2015-11-01

    To analyze influenza pathogen spectrum in Yunnan province during 2009-2014 years, and analyze HA and NA genes of influenza A H1N1. Analysis was made on the monitoring date of influenza cases in Yunnan province in recent 6 years, 23 strains of influenza virus of HA and NA gene was sequenced and analyzed by MEGA 5 software to construct phylogenetic tree. 4 times of influenza AH1N1 epidemic peak were monitored from 2009-2014 years in Yunnan Province, as the nucleic acid detection results of influenza A H1N1 accounted for 28.8% of the total. The sequencing result showed that HA and NA gene were divided into 3 groups, one was detected with H275Y mutation strains. Influenza A H1N1 is one of the important subtypes in Yunnan province and their genes have divided into three branches during the period of 2009-2014 years, the vast majority of influenza a H1N1 are still sensitive to neuraminidase inhibitors.

  1. A PB1 T296R substitution enhance polymerase activity and confer a virulent phenotype to a 2009 pandemic H1N1 influenza virus in mice.

    Science.gov (United States)

    Yu, Zhijun; Cheng, Kaihui; Sun, Weiyang; Zhang, Xinghai; Li, Yuanguo; Wang, Tiecheng; Wang, Hualei; Zhang, Qianyi; Xin, Yue; Xue, Li; Zhang, Kun; Huang, Jing; Yang, Songtao; Qin, Chuan; Wilker, Peter R; Yue, Donghui; Chen, Hualan; Gao, Yuwei; Xia, Xianzhu

    2015-12-01

    While the 2009 pandemic H1N1 virus has become established in the human population as a seasonal influenza virus, continued adaptation may alter viral virulence. Here, we passaged a 2009 pandemic H1N1 virus (A/Changchun/01/2009) in mice. Serial passage in mice generated viral variants with increased virulence. Adapted variants displayed enhanced replication kinetics in vitro and vivo. Analysis of the variants genomes revealed 6 amino acid changes in the PB1 (T296R), PA (I94V), HA (H3 numbering; N159D, D225G, and R226Q), and NP (D375N). Using reverse genetics, we found that a PB1-T296R substitution found in all adapted viral variants enhanced viral replication kinetics in vitro and vivo, increased viral polymerase activity in human cells, and was sufficient for enhanced virulence of the 2009 pandemic H1N1 virus in mice. Therefore, we defined a novel influenza pathogenic determinant, providing further insights into the pathogenesis of influenza viruses in mammals.

  2. H1N1 influenza virus induces narcolepsy-like sleep disruption and targets sleep-wake regulatory neurons in mice.

    Science.gov (United States)

    Tesoriero, Chiara; Codita, Alina; Zhang, Ming-Dong; Cherninsky, Andrij; Karlsson, Håkan; Grassi-Zucconi, Gigliola; Bertini, Giuseppe; Harkany, Tibor; Ljungberg, Karl; Liljeström, Peter; Hökfelt, Tomas G M; Bentivoglio, Marina; Kristensson, Krister

    2016-01-19

    An increased incidence in the sleep-disorder narcolepsy has been associated with the 2009-2010 pandemic of H1N1 influenza virus in China and with mass vaccination campaigns against influenza during the pandemic in Finland and Sweden. Pathogenetic mechanisms of narcolepsy have so far mainly focused on autoimmunity. We here tested an alternative working hypothesis involving a direct role of influenza virus infection in the pathogenesis of narcolepsy in susceptible subjects. We show that infection with H1N1 influenza virus in mice that lack B and T cells (Recombinant activating gene 1-deficient mice) can lead to narcoleptic-like sleep-wake fragmentation and sleep structure alterations. Interestingly, the infection targeted brainstem and hypothalamic neurons, including orexin/hypocretin-producing neurons that regulate sleep-wake stability and are affected in narcolepsy. Because changes occurred in the absence of adaptive autoimmune responses, the findings show that brain infections with H1N1 virus have the potential to cause per se narcoleptic-like sleep disruption.

  3. Titering of 2009 pandemic H1N1 influenza virus hemagglutinin inhibition antibody in nonvaccinated pregnant women in Shiraz, Southern Iran.

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    Honarvar, Behnam; Moghadami, Mohsen; Moattari, Afagh; Emami, Amir; Tabatabaee, Hamid Reza; Jahromi, Bahia Namavar; Asadi, Nasrin; Mousavizadeh, Ali; Lankarani, Kamran Bagheri; Joulaei, Hassan; Ghaffarpasand, Fariborz

    2012-05-01

    Influenza may cause severe complications for pregnant women. In this study antibody response against 2009 H1N1 influenza virus in pregnant women was investigated. This seroprevalance cross sectional and questionnaire based study was conducted using a convenient sampling method. Blood samples of pregnant women were checked for antibodies against 2009 H1N1 influenza virus using hemagglutination inhibition assay. An antibody titer level of ≥ 1:40 dilution was considered as the protective level. 167 (43.60%) of 383 pregnant women who participated in this study had protective antibody levels against this virus. 62 (35.63%) of 3rd trimester, 79 (46.74%) of 2nd trimester, and 21(52.50%) of 1st trimester pregnant women were immune respectively (χ2(for trend) = 8.20, p pregnant women of 3rd trimester of pregnancy (OR = 2.37, CI = 1.09-5.18). Pregnant women with higher education (OR = 1.67, CI = 1.02-2.73) and those with history of anemia (OR = 2.09, CI = 1.18-3.68) had more immunity. Older women (OR = 0.95, CI = 0.91-0.99) and those with history of psychological diseases (OR = 0.19, CI = 0.05-0.70) had less immunity. Vaccination of pregnant women, especially those who are in the higher trimesters of pregnancy, older, or less educated, against the 2009 H1N1 influenza virus should be continued.

  4. An equine herpesvirus 1 (EHV-1) vectored H1 vaccine protects against challenge with swine-origin influenza virus H1N1.

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    Said, Abdelrahman; Damiani, Armando; Ma, Guanggang; Kalthoff, Donata; Beer, Martin; Osterrieder, Nikolaus

    2011-12-29

    In 2009, a novel swine-origin H1N1 influenza A virus (S-OIV), antigenically and genetically divergent from seasonal H1N1, caused a flu pandemic in humans. Development of an effective vaccine to limit transmission of S-OIV in animal reservoir hosts and from reservoir hosts to humans and animals is necessary. In the present study, we constructed and evaluated a vectored vaccine expressing the H1 hemagglutinin of a recent S-OIV isolate using equine herpesvirus 1 (EHV-1) as the delivery vehicle. Expression of the recombinant protein was demonstrated by immunofluorescence and western blotting and the in vitro growth properties of the modified live vector were found to be comparable to those of the parental virus. The EHV-1-H1 vaccine induced an influenza virus-specific antibody response when inoculated into mice by both the intranasal and subcutaneous routes. Upon challenge infection, protection of vaccinated mice could be demonstrated by reduction of clinical signs and faster virus clearance. Our study shows that an EHV-1-based influenza H1N1 vaccine may be a promising alternative for protection against S-OIV infection.

  5. Risk factors for adult death due to 2009 pandemic influenza A (H1N1) virus infection: a 2151 severe and critical cases analysis

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    ZHANG Peng-jun; CAO Bin; LI Xiao-li; LIANG Li-rong; YANG Shi-gui; GU Li; XU Zhen

    2013-01-01

    Background The 2009 pandemic H1 N1 (pH1N1) influenza showed that relatively young adults accounted for the highest rates of hospital admission and death.In preparation for pH1N1,the aim of the study is to identify factors associated with the mortality of patients with 2009 pH1N1 infection,especially for young patients without chronic medical conditions.Methods Retrospective observational study of 2151 severe or critical adult cases (-≥14 years old) admitted to a hospital with pH1N1 influenza from September 1,2009 to December 31,2009 from 426 hospitals of 27 Chinese provinces.A confirmed case was a person whose pH1N1 virus infection was verified by real-time reverse-transcriptase polymerase chain reaction (rRT-PCR).Severe and critical cases were defined according to the H1N1 2009 Clinical guidelines (Third Edition,2009) released by the Ministry of Health of China.Results Among the 2151 patients,the mean age was 34.0 years.Two hundred and ninty-three (13.6%) died during hospital stay.One thousand four hundred and forty-two patients (67.0%) had no comorbidities and 189 (13.1%) of them died.Pregnancy (OR 8.03),pneumonia (OR 8.91),dyspnea (OR 3.95),central nervous system (CNS) symptom (OR 1.55),higher APACHE (Acute Physiology and Chronic Health Evaluation) Ⅱ score (OR 1.06),Alanine aminotransferase (ALT) (OR 1.002),and the lactate dehydrogenase (LDH) level (OR 1.001) were independent risk factors for death among adults without chronic medical conditions.Higher APACHE Ⅱ score (OR 1.08) and age (OR 1.06) were independent risk factors for death among adults with respiratory diseases.A multivariate analysis showed an association between mortality and CNS symptoms (OR 2.66),higher APACHE Ⅱ score (OR 1.03),ALT (OR 1.006),and LDH level (OR 1.002) in patients with cardiovascular diseases.Dyspnea (OR 11.32) was an independent risk factor for patient death in patients with diabetes mellitus.Conclusion Clinical knowledge of identified prognostic factors for mortality

  6. 实时荧光RT-PCR检测不同标本中甲型H1N1流感病毒核酸的临床意义%Clinical significance of fluorescent real-time RT-PCR in the detection of influenza A virus (H1N1) nucleic acid in different types of specimens

    Institute of Scientific and Technical Information of China (English)

    陈双峰; 陈海英; 张颖新; 郑丽丽

    2011-01-01

    Objective To explore the relationship of influenza A virus ( H1N1) nucleic acid with rapid diagnosis of influenza A ( H1N1) and the progress of disease course by the detection of viral nucleic acid in different specimens from patients with influenza A ( H1N1). Methods Fluorescent real-time reverse transcription polymerase chain reaction (RT-PCR) was performed to detect influenza A virus ( H1N1) nucleic acid in throat swabs, plasma and secretion of lower respiratory tract from 118 patients with influenza A ( H1N1) 48 hours after onset and (or) during convalescence respectively. Results Viral nucleic acid was detected in throat swabs from all 118 patients 48 hours after onset,secretion of lower respiratory tract from 23 severe cases and plasma from 15 severe cases. Coriclusion Fluorescent real -time RT-PCR could be used for the rapid detection of influenza A virus ( H1N1) infection. Influenza A virus (H1N1) nucleic acid,when be detected in plasma,may be the indication of the severe cases.%目的 通过检测甲型H1N1流感感染患者不同标本中甲型H1N1流感病毒核酸,了解其对甲型H1N1流感的快速诊断及病程进展的关系.方法 118例甲型H1N1流感患者,采用实时荧光逆转录聚合酶链反应法(RT-PCR)分别检测发病48 h后和(或)恢复期咽拭子、血浆及下呼吸道分泌物中甲型H1N1流感病毒核酸.结果 118例甲型H1N1流感患者发病48 h后咽拭子甲型H1N1流感病毒核酸阳性;23例(23/40)重症患者下呼吸道分泌物中甲型H1N1流感病毒核酸阳性;15例(15/40)重症患者血浆中检测到甲型H1N1流感病毒核酸.结论 实时荧光RT-PCR方法可以快速检测甲型H1N1流感病毒感染,血浆中甲型H1N1流感病毒核酸阳性可能是重症患者的标志.

  7. Vγ4+γδT Cells Aggravate Severe H1N1 Influenza Virus Infection-Induced Acute Pulmonary Immunopathological Injury via Secreting Interleukin-17A

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    Chunxue Xue

    2017-08-01

    Full Text Available The influenza A (H1N1 pdm09 virus remains a critical global health concern and causes high levels of morbidity and mortality. Severe acute lung injury (ALI and acute respiratory distress syndrome (ARDS are the major outcomes among severely infected patients. Our previous study found that interleukin (IL-17A production by humans or mice infected with influenza A (H1N1 pdm09 substantially contributes to ALI and subsequent morbidity and mortality. However, the cell types responsible for IL-17A production during the early stage of severe influenza A (H1N1 pdm09 infection remained unknown. In this study, a mouse model of severe influenza A (H1N1 pdm09 infection was established. Our results show that, in the lungs of infected mice, the percentage of γδT cells, but not the percentages of CD4+Th and CD8+Tc cells, gradually increased and peaked at 3 days post-infection (dpi. Further analysis revealed that the Vγ4+γδT subset, but not the Vγ1+γδT subset, was significantly increased among the γδT cells. At 3 dpi, the virus induced significant increases in IL-17A in the bronchoalveolar lavage fluid (BALF and serum. IL-17A was predominantly secreted by γδT cells (especially the Vγ4+γδT subset, but not CD4+Th and CD8+Tc cells at the early stage of infection, and IL-1β and/or IL-23 were sufficient to induce IL-17A production by γδT cells. In addition to secreting IL-17A, γδT cells secreted interferon (IFN-γ and expressed both an activation-associated molecule, natural killer group 2, member D (NKG2D, and an apoptosis-associated molecule, FasL. Depletion of γδT cells or the Vγ4+γδT subset significantly rescued the virus-induced weight loss and improved the survival rate by decreasing IL-17A secretion and reducing immunopathological injury. This study demonstrated that, by secreting IL-17A, lung Vγ4+γδT cells, at least, in part mediated influenza A (H1N1 pdm09-induced immunopathological injury. This mechanism might serve as a

  8. High burden of non-influenza viruses in influenza-like illness in the early weeks of H1N1v epidemic in France.

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    Nathalie Schnepf

    Full Text Available BACKGROUND: Influenza-like illness (ILI may be caused by a variety of pathogens. Clinical observations are of little help to recognise myxovirus infection and implement appropriate prevention measures. The limited use of molecular tools underestimates the role of other common pathogens. OBJECTIVES: During the early weeks of the 2009-2010 flu pandemic, a clinical and virological survey was conducted in adult and paediatric patients with ILI referred to two French University hospitals in Paris and Tours. Aims were to investigate the different pathogens involved in ILI and describe the associated symptoms. METHODS: H1N1v pandemic influenza diagnosis was performed with real time RT-PCR assay. Other viral aetiologies were investigated by the molecular multiplex assay RespiFinder19®. Clinical data were collected prospectively by physicians using a standard questionnaire. RESULTS: From week 35 to 44, endonasal swabs were collected in 413 patients. Overall, 68 samples (16.5% were positive for H1N1v. In 13 of them, other respiratory pathogens were also detected. Among H1N1v negative samples, 213 (61.9% were positive for various respiratory agents, 190 in single infections and 23 in mixed infections. The most prevalent viruses in H1N1v negative single infections were rhinovirus (62.6%, followed by parainfluenza viruses (24.2% and adenovirus (5.3%. 70.6% of H1N1v cases were identified in patients under 40 years and none after 65 years. There was no difference between clinical symptoms observed in patients infected with H1N1v or with other pathogens. CONCLUSION: Our results highlight the high frequency of non-influenza viruses involved in ILI during the pre-epidemic period of a flu alert and the lack of specific clinical signs associated with influenza infections. Rapid diagnostic screening of a large panel of respiratory pathogens may be critical to define and survey the epidemic situation and to provide critical information for patient management.

  9. Prophylactic and therapeutic efficacy of avian antibodies against influenza virus H5N1 and H1N1 in mice.

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    Huan H Nguyen

    Full Text Available BACKGROUND: Pandemic influenza poses a serious threat to global health and the world economy. While vaccines are currently under development, passive immunization could offer an alternative strategy to prevent and treat influenza virus infection. Attempts to develop monoclonal antibodies (mAbs have been made. However, passive immunization based on mAbs may require a cocktail of mAbs with broader specificity in order to provide full protection since mAbs are generally specific for single epitopes. Chicken immunoglobulins (IgY found in egg yolk have been used mainly for treatment of infectious diseases of the gastrointestinal tract. Because the recent epidemic of highly pathogenic avian influenza virus (HPAIV strain H5N1 has resulted in serious economic losses to the poultry industry, many countries including Vietnam have introduced mass vaccination of poultry with H5N1 virus vaccines. We reasoned that IgY from consumable eggs available in supermarkets in Vietnam could provide protection against infections with HPAIV H5N1. METHODS AND FINDINGS: We found that H5N1-specific IgY that are prepared from eggs available in supermarkets in Vietnam by a rapid and simple water dilution method cross-protect against infections with HPAIV H5N1 and related H5N2 strains in mice. When administered intranasally before or after lethal infection, the IgY prevent the infection or significantly reduce viral replication resulting in complete recovery from the disease, respectively. We further generated H1N1 virus-specific IgY by immunization of hens with inactivated H1N1 A/PR/8/34 as a model virus for the current pandemic H1N1/09 and found that such H1N1-specific IgY protect mice from lethal influenza virus infection. CONCLUSIONS: The findings suggest that readily available H5N1-specific IgY offer an enormous source of valuable biological material to combat a potential H5N1 pandemic. In addition, our study provides a proof-of-concept for the approach using virus

  10. In silico molecular modeling of neuraminidase enzyme H1N1 avian influenza virus and docking with zanamivir ligands

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    Muthiyan Ramachandran

    2012-12-01

    Full Text Available Objective: Neuraminidase is an enzyme aspartic protease that is essential for the life cycle of H1N1. Methods: Constructed a model of Neuraminidase enzyme the 3D structure as template using with Modeller software. The Neuraminidase enzyme model was predicted and validated by Procheck, What check, Errat, Verify-3D and AutoDock web server for reliability. Results: The Modeller homology-modeling algorithm was demonstrated excellent accuracy in blind predictions. The Neuraminidase enzyme model built with little, 35% identity could be accurate enough to be successfully used in receptor based rational drug design. The closest homologue with the highest sequence identity 100% was selected. Zanamivir drug and analogues were retrieved from PubChem database, as well as subjected to docking interaction with Neuraminidase enzyme used AutoDock programme. Based on the root mean square deviation and lowest binding energy values the best docking orientation was selected. The better lowest binding energy value -6.91 was selected of CID_25209232. Conclusions: This study will be used in broad screening of inhibitors of the protein. However, further implemented experimental and clinical verification is needed to establishment these analogues as drug.

  11. Assessing Antigenic Drift of Seasonal Influenza A(H3N2) and A(H1N1)pdm09 Viruses.

    Science.gov (United States)

    Tewawong, Nipaporn; Prachayangprecha, Slinporn; Vichiwattana, Preeyaporn; Korkong, Sumeth; Klinfueng, Sirapa; Vongpunsawad, Sompong; Thongmee, Thanunrat; Theamboonlers, Apiradee; Poovorawan, Yong

    2015-01-01

    Under selective pressure from the host immune system, antigenic epitopes of influenza virus hemagglutinin (HA) have continually evolved to escape antibody recognition, termed antigenic drift. We analyzed the genomes of influenza A(H3N2) and A(H1N1)pdm09 virus strains circulating in Thailand between 2010 and 2014 and assessed how well the yearly vaccine strains recommended for the southern hemisphere matched them. We amplified and sequenced the HA gene of 120 A(H3N2) and 81 A(H1N1)pdm09 influenza virus samples obtained from respiratory specimens and calculated the perfect-match vaccine efficacy using the pepitope model, which quantitated the antigenic drift in the dominant epitope of HA. Phylogenetic analysis of the A(H3N2) HA1 genes classified most strains into genetic clades 1, 3A, 3B, and 3C. The A(H3N2) strains from the 2013 and 2014 seasons showed very low to moderate vaccine efficacy and demonstrated antigenic drift from epitopes C and A to epitope B. Meanwhile, most A(H1N1)pdm09 strains from the 2012-2014 seasons belonged to genetic clades 6A, 6B, and 6C and displayed the dominant epitope mutations at epitopes B and E. Finally, the vaccine efficacy for A(H1N1)pdm09 (79.6-93.4%) was generally higher than that of A(H3N2). These findings further confirmed the accelerating antigenic drift of the circulating influenza A(H3N2) in recent years.

  12. Fully human broadly neutralizing monoclonal antibodies against influenza A viruses generated from the memory B cells of a 2009 pandemic H1N1 influenza vaccine recipient

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Weibin [Molecular Virus Unit, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200025 (China); Chen, Aizhong [Key Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031 (China); Miao, Yi [Shanghai Xuhui Central Hospital, Shanghai 200031 (China); Xia, Shengli [Center for Disease Control and Prevention of Henan Province, Zhengzhou 450016 (China); Ling, Zhiyang; Xu, Ke; Wang, Tongyan [Molecular Virus Unit, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200025 (China); Xu, Ying; Cui, Jun; Wu, Hongqiang; Hu, Guiyu; Tian, Lin; Wang, Lingling [Key Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031 (China); Shu, Yuelong [Chinese Center for Disease Control and Prevention, Beijing 102206 (China); Ma, Xiaowei [Hualan Biological Bacterin Company, Xinxiang 453003 (China); Xu, Bianli; Zhang, Jin [Center for Disease Control and Prevention of Henan Province, Zhengzhou 450016 (China); Lin, Xiaojun, E-mail: linxiaojun@hualan.com [Hualan Biological Bacterin Company, Xinxiang 453003 (China); Bian, Chao, E-mail: cbian@sibs.ac.cn [Key Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031 (China); Sun, Bing, E-mail: bsun@sibs.ac.cn [Molecular Virus Unit, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200025 (China); Key Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031 (China)

    2013-01-20

    Whether the 2009 pandemic H1N1 influenza vaccine can induce heterosubtypic cross-protective anti-hemagglutinin (HA) neutralizing antibodies is an important issue. We obtained a panel of fully human monoclonal antibodies from the memory B cells of a 2009 pandemic H1N1 influenza vaccine recipient. Most of the monoclonal antibodies targeted the HA protein but not the HA1 fragment. Among the analyzed antibodies, seven mAbs exhibited neutralizing activity against several influenza A viruses of different subtypes. The conserved linear epitope targeted by the neutralizing mAbs (FIEGGWTGMVDGWYGYHH) is part of the fusion peptide on HA2. Our work suggests that a heterosubtypic neutralizing antibody response primarily targeting the HA stem region exists in recipients of the 2009 pandemic H1N1 influenza vaccine. The HA stem region contains various conserved neutralizing epitopes with the fusion peptide as an important one. This work may aid in the design of a universal influenza A virus vaccine.

  13. Evaluation of seasonal influenza vaccines for H1N1pdm09 and type B viruses based on a replication-incompetent PB2-KO virus.

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    Ui, Hiroki; Yamayoshi, Seiya; Uraki, Ryuta; Kiso, Maki; Oishi, Kohei; Murakami, Shin; Mimori, Shigetaka; Kawaoka, Yoshihiro

    2017-04-04

    Vaccination is the first line of protection against influenza virus infection in humans. Although inactivated and live-attenuated vaccines are available, each vaccine has drawbacks in terms of immunogenicity and safety. To overcome these issues, our group has developed a replication-incompetent PB2-knockout (PB2-KO) influenza virus that replicates only in PB2-expressing cells. Here we generated PB2-KO viruses possessing the hemagglutinin (HA) and neuraminidase (NA) segments from H1N1pdm09 or type B viruses and tested their vaccine potential. The two PB2-KO viruses propagated efficiently in PB2-expressing cells, and expressed chimeric HA as expected. Virus-specific IgG and IgA antibodies were detected in mice immunized with the viruses, and the immunized mice showed milder clinical signs and/or lower virus replication levels in the respiratory tract upon virus challenge. Our results indicate that these PB2-KO viruses have potential as vaccine candidates. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Transmission and pathogenicity of novel reassortants derived from Eurasian avian-like and 2009 pandemic H1N1 influenza viruses in mice and guinea pigs.

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    Kong, Weili; Liu, Qinfang; Sun, Yipeng; Wang, Yu; Gao, Huijie; Liu, Lirong; Qin, Zhihua; He, Qiming; Sun, Honglei; Pu, Juan; Wang, Dayan; Guo, Xin; Yang, Hanchun; Chang, Kin-Chow; Shu, Yuelong; Liu, Jinhua

    2016-06-02

    Given the present extensive co-circulation in pigs of Eurasian avian-like (EA) swine H1N1 and 2009 pandemic (pdm/09) H1N1 viruses, reassortment between them is highly plausible but largely uncharacterized. Here, experimentally co-infected pigs with a representative EA virus and a pdm/09 virus yielded 55 novel reassortant viruses that could be categorized into 17 genotypes from Gt1 to Gt17 based on segment segregation. Majority of novel reassortants were isolated from the lower respiratory tract. Most of reassortant viruses were more pathogenic and contagious than the parental EA viruses in mice and guinea pigs. The most transmissible reassortant genotypes demonstrated in guinea pigs (Gt2, Gt3, Gt7, Gt10 and Gt13) were also the most lethal in mice. Notably, nearly all these highly virulent reassortants (all except Gt13) were characterized with possession of EA H1 and full complement of pdm/09 ribonucleoprotein genes. Compositionally, we demonstrated that EA H1-222G contributed to virulence by its ability to bind avian-type sialic acid receptors, and that pdm/09 RNP conferred the most robust polymerase activity to reassortants. The present study revealed high reassortment compatibility between EA and pdm/09 viruses in pigs, which could give rise to progeny reassortant viruses with enhanced virulence and transmissibility in mice and guinea pig models.

  15. Isolation of a high affinity neutralizing monoclonal antibody against 2009 pandemic H1N1 virus that binds at the 'Sa' antigenic site.

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    Nachiket Shembekar

    Full Text Available Influenza virus evades host immunity through antigenic drift and shift, and continues to circulate in the human population causing periodic outbreaks including the recent 2009 pandemic. A large segment of the population was potentially susceptible to this novel strain of virus. Historically, monoclonal antibodies (MAbs have been fundamental tools for diagnosis and epitope mapping of influenza viruses and their importance as an alternate treatment option is also being realized. The current study describes isolation of a high affinity (K(D = 2.1±0.4 pM murine MAb, MA2077 that binds specifically to the hemagglutinin (HA surface glycoprotein of the pandemic virus. The antibody neutralized the 2009 pandemic H1N1 virus in an in vitro microneutralization assay (IC(50 = 0.08 µg/ml. MA2077 also showed hemagglutination inhibition activity (HI titre of 0.50 µg/ml against the pandemic virus. In a competition ELISA, MA2077 competed with the binding site of the human MAb, 2D1 (isolated from a survivor of the 1918 Spanish flu pandemic on pandemic H1N1 HA. Epitope mapping studies using yeast cell-surface display of a stable HA1 fragment, wherein 'Sa' and 'Sb' sites were independently mutated, localized the binding site of MA2077 within the 'Sa' antigenic site. These studies will facilitate our understanding of antigen antibody interaction in the context of neutralization of the pandemic influenza virus.

  16. Induction of microglia activation after infection with the non-neurotropic A/CA/04/2009 H1N1 influenza virus.

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    Shankar Sadasivan

    Full Text Available Although influenza is primarily a respiratory disease, it has been shown, in some cases, to induce encephalitis, including people acutely infected with the pandemic A/California/04/2009 (CA/09 H1N1 virus. Based on previous studies showing that the highly pathogenic avian influenza (HPAI A/Vietnam/1203/2004 H5N1 virus was neurotropic, induced CNS inflammation and a transient parkinsonism, we examined the neurotropic and inflammatory potential of the CA/09 H1N1 virus in mice. Following intranasal inoculation, we found no evidence for CA/09 H1N1 virus neurotropism in the enteric, peripheral or central nervous systems. We did, however, observe a robust increase in microglial activity in the brain characterized by an increase in the number of activated Iba-1-positive microglia in the substantia nigra (SN and the hippocampus, despite the absence of virus in the brain. qPCR analysis in SN tissue showed that the induction of microgliosis was preceded by reduced gene expression of the neurotrophic factors bdnf, and gdnf and increases in the immune modulatory chemokine chemokine (C-C motif ligand 4 (ccl4. We also noted changes in the expression of transforming growth factor-1 (tgfβ1 in the SN starting at 7 days post-infection (dpi that was sustained through 21 dpi, coupled with increases in arginase-1 (arg1 and csf1, M2 markers for microglia. Given that neuroinflammation contributes to generation and progression of a number of neurodegenerative disorders, these findings have significant implications as they highlight the possibility that influenza and perhaps other non-neurotropic viruses can initiate inflammatory signals via microglia activation in the brain and contribute to, but not necessarily be the primary cause of, neurodegenerative disorders.

  17. Sequence-based identification and characterization of nosocomial influenza A(H1N1)pdm09 virus infections

    NARCIS (Netherlands)

    Jonges, M.; Rahamat-Langendoen, J.; Meijer, A.; Niesters, H. G.; Koopmans, M.

    2012-01-01

    Background: Highly transmissible viruses such as influenza are a potential source of nosocomial infections and thereby cause increased patient morbidity and mortality. Aim: To assess whether influenza virus sequence data can be used to link nosocomial influenza transmission between individuals.

  18. Phenotypic differences in virulence and immune response in closely related clinical isolates of influenza A 2009 H1N1 pandemic viruses in mice.

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    Jeremy V Camp

    Full Text Available To capture the possible genotypic and phenotypic differences of the 2009 influenza A virus H1N1 pandemic (H1N1pdm strains circulating in adult hospitalized patients, we isolated and sequenced nine H1N1pdm viruses from patients hospitalized during 2009-2010 with severe influenza pneumonia in Kentucky. Each viral isolate was characterized in mice along with two additional H1N1 pandemic strains and one seasonal strain to assess replication and virulence. All isolates showed similar levels of replication in nasal turbinates and lung, but varied in their ability to cause morbidity. Further differences were identified in cytokine and chemokine responses. IL-6 and KC were expressed early in mice infected with strains associated with higher virulence. Strains that showed lower pathogenicity in mice had greater IFNγ, MIG, and IL-10 responses. A principal component analysis (PCA of the cytokine and chemokine profiles revealed 4 immune response phenotypes that correlated with the severity of disease. A/KY/180/10, which showed the greatest virulence with a rapid onset of disease progression, was compared in additional studies with A/KY/136/09, which showed low virulence in mice. Analyses comparing a low (KY/136 versus a high (KY/180 virulent isolate showed a significant difference in the kinetics of infection within the lower respiratory tract and immune responses. Notably by 4 DPI, virus titers within the lung, bronchoalveolar lavage fluid (BALf, and cells within the BAL (BALc revealed that the KY/136 replicated in BALc, while KY/180 replication persisted in lungs and BALc. In summary, our studies suggest four phenotypic groups based on immune responses that result in different virulence outcomes in H1N1pdm isolates with a high degree of genetic similarity. In vitro studies with two of these isolates suggested that the more virulent isolate, KY/180, replicates productively in macrophages and this may be a key determinant in tipping the response toward a

  19. Mapping the sequence mutations of the 2009 H1N1 influenza A virus neuraminidase relative to drug and antibody binding sites

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    Sirota Fernanda L

    2009-05-01

    Full Text Available Abstract In this work, we study the consequences of sequence variations of the "2009 H1N1" (swine or Mexican flu influenza A virus strain neuraminidase for drug treatment and vaccination. We find that it is phylogenetically more closely related to European H1N1 swine flu and H5N1 avian flu rather than to the H1N1 counterparts in the Americas. Homology-based 3D structure modeling reveals that the novel mutations are preferentially located at the protein surface and do not interfere with the active site. The latter is the binding cavity for 3 currently used neuraminidase inhibitors: oseltamivir (Tamiflu®, zanamivir (Relenza® and peramivir; thus, the drugs should remain effective for treatment. However, the antigenic regions of the neuraminidase relevant for vaccine development, serological typing and passive antibody treatment can differ from those of previous strains and already vary among patients. Reviewers This article was reviewed by Sandor Pongor and L. Aravind.

  20. 免疫层析法用于甲型H1N1流感病毒抗原筛查的初步评价%Primary evaluation of immunochromatographic assay for the screening of influenza A virus H1N1 antigen

    Institute of Scientific and Technical Information of China (English)

    石汉振; 郑智明; 黄宪章; 方静

    2011-01-01

    Objective To evaluate the accuracy of the immunochromatographic assay for the detection of influenza A virus H1N1 antigen, and use it into clinical application.Methods 356 nasal mucus samples from patients suspected with influenza A were collected from Guangdong Provincial Hospital of Chinese Medicine from August to December 2009.The influenza A virus H1N1 antigen was detected by the immunochromatographic assay.The patients' pharynx samples were send to Guangzhou Center for Disease Control and Prevention ( CDC ) for the detection of influenza A virus H1N1 gene.Results The results showed that 108 cases were positive of influenza A virus H1N1 antigen by the immunochromatographic assay, and 92 cases were confirmed as positive of influenza A H1 N1 gene in CDC.There were 248 cases with negative influenza A H1N1 antigen, and 264 cases were confirmed by influenza A H1N1 gene.The sensitivity, specificity, false positive rate and false negative rate were 96.7%, 92.8%, 17.6% and 1.2%,respectively.Conclusions The immunochromatographic assay is rapid and simple for screening influenza A virus H1N1.However, the assay may show some false positive and negative results, and it can't be used for confirmatory test.%目的 评估免疫层析法检测甲型H1N1流感病毒抗原的准确性,推广免疫层析法在甲流H1N1抗原检测中的临床应用.方法 收集2009年8至12月广东省中医院356例甲型H1N1流感疑似患者的鼻拭子标本,采用免疫层析法进行甲型H1N1流感病毒抗原的快速检测,同时将患者咽拭子送往广州市疾病预防控制中心(CDC)进行甲型H1N1流感病毒核酸检测.结果 356例甲型H1N1流感疑似病例标本中,免疫层析法阳性108例,CDC确诊阳性92例;免疫层析法阴性248例,CDC确诊阴性264例.免疫层析法敏感性为96.7%,特异性为92.8%,假阳性率为17.6%,假阴性率为1.2%.结论 免疫层析法操作简便,能对甲型H1N1流感患者进行快速筛查,但存在一定的假阳性

  1. INFECCIÓN POR VIRUS DE LA GRIPE A H1N1NV EN ELCOMPLEJO ASISTENCIAL UNIVERSITARIO DE BURGOSDESDE DICIEMBRE DE 2010 A MARZO DE 2011

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    Megías Lobón G

    2012-01-01

    Full Text Available SUMMARY: INFLUENZA A H1N1NV INFECTION IN A BURGOS HOSPITAL FROM DECEMBER 2010 TO MARCH 2011 Introduction: Monitoring and characterization of infection with pandemic (H1N1nv 2009 is an essential part of monitoring the evolution, epidemiology and severity of a pandemic. The aim of this paper is to describe and analyze the clinical characteristics and risk factors of patients admitted to our hospital the 2010-2011 season. Methods: Detection of influenza A H1N1nv virus in 266 respiratory specimens (242 patients with suspected infection and descriptive and comparative analysis of data collected from each patient: age, sex, service, reason for admission, risk factors and treatment with antivirals. Results: The most common reason for admission (52.47% was the presence of clinical respiratory signs. 69.4% of patients had risk factors, with chronic respiratory disease (CRD, the most frequent (20.2%. 14.2% were pediatric patients. The infection of Influenza A H1N1nv was confirmed in 26,4% of patients. The mean age among the infected patients was 36 years versus 44.85 years in non-infected. This difference was statistically significant (p = 0.011. 75% of infected patients had risk factors. Of these, 68.7% had CRD only factor being predominant. 6% of patients with infection were vaccinated. Conclusion: The positivity rate was similar to that observed in the previous season. There was a greater involvement among young-adult population. The CRD is the most common risk factor. Vaccine coverage was low.

  2. Entrapment of H1N1 Influenza Virus Derived Conserved Peptides in PLGA Nanoparticles Enhances T Cell Response and Vaccine Efficacy in Pigs.

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    Jagadish Hiremath

    Full Text Available Pigs are believed to be one of the important sources of emerging human and swine influenza viruses (SwIV. Influenza virus conserved peptides have the potential to elicit cross-protective immune response, but without the help of potent adjuvant and delivery system they are poorly immunogenic. Biodegradable polylactic-co-glycolic acid (PLGA nanoparticle (PLGA-NP based vaccine delivery system enhances cross-presentation of antigens by the professional antigen presenting cells. In this study, Norovirus P particle containing SwIV M2e (extracellular domain of the matrix protein 2 chimera and highly conserved two each of H1N1 peptides of pandemic 2009 and classical human influenza viruses were entrapped in PLGA-NPs. Influenza antibody-free pigs were vaccinated with PLGA-NPs peptides cocktail vaccine twice with or without an adjuvant, Mycobacterium vaccae whole cell lysate, intranasally as mist. Vaccinated pigs were challenged with a virulent heterologous zoonotic SwIV H1N1, and one week later euthanized and the lung samples were analyzed for the specific immune response and viral load. Clinically, pigs vaccinated with PLGA-NP peptides vaccine had no fever and flu symptoms, and the replicating challenged SwIV was undetectable in the bronchoalveolar lavage fluid. Immunologically, PLGA-NP peptides vaccination (without adjuvant significantly increased the frequency of antigen-specific IFNγ secreting CD4 and CD8 T cells response in the lung lymphocytes, despite not boosting the antibody response both at pre- and post-challenge. In summary, our data indicated that nanoparticle-mediated delivery of conserved H1N1 influenza peptides induced the virus specific T cell response in the lungs and reduced the challenged heterologous virus load in the airways of pigs.

  3. Antigenic and genomic characterization of human influenza A and B viruses circulating in Argentina after the introduction of influenza A(H1N1)pdm09.

    Science.gov (United States)

    Russo, Mara L; Pontoriero, Andrea V; Benedetti, Estefania; Czech, Andrea; Avaro, Martin; Periolo, Natalia; Campos, Ana M; Savy, Vilma L; Baumeister, Elsa G

    2014-12-01

    This study was conducted as part of the Argentinean Influenza and other Respiratory Viruses Surveillance Network, in the context of the Global Influenza Surveillance carried out by the World Health Organization (WHO). The objective was to study the activity and the antigenic and genomic characteristics of circulating viruses for three consecutive seasons (2010, 2011 and 2012) in order to investigate the emergence of influenza viral variants. During the study period, influenza virus circulation was detected from January to December. Influenza A and B, and all current subtypes of human influenza viruses, were present each year. Throughout the 2010 post-pandemic season, influenza A(H1N1)pdm09, unexpectedly, almost disappeared. The haemagglutinin (HA) of the A(H1N1)pdm09 viruses studied were segregated in a different genetic group to those identified during the 2009 pandemic, although they were still antigenically closely related to the vaccine strain A/California/07/2009. Influenza A(H3N2) viruses were the predominant strains circulating during the 2011 season, accounting for nearly 76 % of influenza viruses identified. That year, all HA sequences of the A(H3N2) viruses tested fell into the A/Victoria/208/2009 genetic clade, but remained antigenically related to A/Perth/16/2009 (reference vaccine recommended for this three-year period). A(H3N2) viruses isolated in 2012 were antigenically closely related to A/Victoria/361/2011, recommended by the WHO as the H3 component for the 2013 Southern Hemisphere formulation. B viruses belonging to the B/Victoria lineage circulated in 2010. A mixed circulation of viral variants of both B/Victoria and B/Yamagata lineages was detected in 2012, with the former being predominant. A(H1N1)pdm09 viruses remained antigenically closely related to the vaccine virus A/California/7/2009; A(H3N2) viruses continually evolved into new antigenic clusters and both B lineages, B/Victoria/2/87-like and B/Yamagata/16/88-like viruses, were observed

  4. Changes and analysis of peripheral white blood cells and lymphocyte subsets for patients with pandemic influenza A virus (H1N1) infection%甲型H1N1流感患者外周血白细胞和淋巴细胞亚群变化分析

    Institute of Scientific and Technical Information of China (English)

    陈威巍; 赵敏; 毛远丽; 谢杨新; 张云辉; 冯艳青; 李伯安; 李波; 洪炜; 刘佳; 马洪滨

    2010-01-01

    目的 探讨甲型H1N1流感患者白细胞和淋巴细胞亚群的变化特点,为甲型H1N1流感的诊断、治疗和预后判断提供实验室依据.方法 采用全血细胞分析和流式细胞分析法分别检测59例甲型H1N1流感患者急性期和恢复期的外周血白细胞及淋巴细胞亚群,与43名健康人和24例普通甲型流感患者比较.结果 甲型H1N1流感轻症患者白细胞总数在急性期显著下降,重症患者白细胞总数下降不显著,而中性粒细胞显著升高;与普通甲型流感相似,所有H1N1流感患者淋巴细胞总数、CD3、CD4、CD8百分比和绝对值在急性期大幅度下降,恢复期迅速回升;而重症患者NK和NKT细胞绝对值在急性期下降幅度超过20%.结论 甲型H1N1流感患者白细胞和淋巴细胞亚群变化与普通甲流相似;急性期NK、NKT细胞绝对值的大幅降低可以提示病情重症化倾向.%Objective To investigate the characters and changes of peripheral white blood cells and lymphocyte subsets of patients with pandemic influenza A virus (H1N1 ) infection and to provide evidences for diagnosis, treatment and prognosis of influenza A ( H1N1 ) infection. Methods Peripheral white blood cell parameters and the percentages of lymphocyte subsets in acute and recovery phases of 59 cases of influenza A virus (H1N1) infectious patients (42 mild cases and 17 severe cases)were investigated and analyzed, and compared respectively with those of 43 cases of healthy adults as control (HC) and 24 cases of general influenza A virus (no-H1N1) infectious using whole blood cell analysis and flow cytometry.Results Peripheral white blood cell counts of mild cases decreased greatly but those of severe cases did not decrease significantly; the neutrophils of severe cases increased significantly in acute phase; similar to general influenza A virus (no-H1N1) infectious, the peripheral lymphocytes, CD3, CD4, CD8 and B cells of all patients with influenza A virus (H1N1) infection

  5. Apoptosis and Proinflammatory Cytokine Responses of Primary Mouse Microglia and Astrocytes Induced by Human H1N1 and Avian H5N1 Influenza Viruses

    Institute of Scientific and Technical Information of China (English)

    Gefei Wang; Kangsheng Li; Juan Zhang; Weizhong Li; Gang Xin; Yun Su; Yuanli Gao; Heng Zhang; Guimei Lin; Xiaoyang Jiao

    2008-01-01

    Patients with an influenza virus infection can be complicated by acute encephalopathy and encephalitis. To investigate the immune reactions involved in the neurocomplication, mouse microglia and astrocytes were isolated,infected with human H1N1 and avian H5N1 influenza viruses, and examined for their immune responses. We observed homogeneously distributed viral receptors, sialic acid (SA)-α2,3-Galactose (Gal) and SA-α2,6-Gal, on microglia and astrocytes. Both viruses were replicative and productive in microglia and astrocytes. Virus-induced apoptosis and cytopathy in infected cells were observed at 24 h post-infection (p.i.). Expression of IL-1β, IL-6 and TNF-α mRNA examined at 6 h and 24 h p.i. Was up-regulated, and their expression levels were considerably higher in H5N1 infection. The amounts of secreted proinflammatory IL-1β, IL-6 and TNF-α at 6 h and 24 h p.i. Were also induced, with greater induction by H5N1 infection. This study is the first demonstration that both human H1N1 and avian H5N1 influenza viruses can infect mouse microglia and astrocytes and induce apoptosis, cytopathy, and proinflammatory cytokine production in them in vitro. Our results suggest that the direct cellular damage and the consequences of immunopathological injury in the CNS contribute to the influenza viral pathogenesis.

  6. Sociodemographic factors and clinical conditions associated to hospitalization in influenza A (H1N1 2009 virus infected patients in Spain, 2009-2010.

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    Fernando González-Candelas

    Full Text Available The emergence and pandemic spread of a new strain of influenza A (H1N1 virus in 2009 resulted in a serious alarm in clinical and public health services all over the world. One distinguishing feature of this new influenza pandemic was the different profile of hospitalized patients compared to those from traditional seasonal influenza infections. Our goal was to analyze sociodemographic and clinical factors associated to hospitalization following infection by influenza A(H1N1 virus. We report the results of a Spanish nationwide study with laboratory confirmed infection by the new pandemic virus in a case-control design based on hospitalized patients. The main risk factors for hospitalization of influenza A (H1N1 2009 were determined to be obesity (BMI≥40, with an odds-ratio [OR] 14.27, hematological neoplasia (OR 10.71, chronic heart disease, COPD (OR 5.16 and neurological disease, among the clinical conditions, whereas low education level and some ethnic backgrounds (Gypsies and Amerinds were the sociodemographic variables found associated to hospitalization. The presence of any clinical condition of moderate risk almost triples the risk of hospitalization (OR 2.88 and high risk conditions raise this value markedly (OR 6.43. The risk of hospitalization increased proportionally when for two (OR 2.08 or for three or more (OR 4.86 risk factors were simultaneously present in the same patient. These findings should be considered when a new influenza virus appears in the human population.

  7. Antiviral activity of chlorogenic acid against influenza A (H1N1/H3N2) virus and its inhibition of neuraminidase

    Science.gov (United States)

    Ding, Yue; Cao, Zeyu; Cao, Liang; Ding, Gang; Wang, Zhenzhong; Xiao, Wei

    2017-01-01

    Lonicera japonica Thunb, rich in chlorogenic acid (CHA), is used for viral upper respiratory tract infection treatment caused by influenza virus, parainfluenza virus, and respiratory syncytial virus, ect in China. It was reported that CHA reduced serum hepatitis B virus level and death rate of influenza virus-infected mice. However, the underlying mechanisms of CHA against the influenza A virus have not been fully elucidated. Here, the antiviral effects and potential mechanisms of CHA against influenza A virus were investigated. CHA revealed inhibitory against A/PuertoRico/8/1934(H1N1) (EC50 = 44.87 μM), A/Beijing/32/92(H3N2) (EC50 = 62.33 μM), and oseltamivir-resistant strains. Time-course analysis showed CHA inhibited influenza virus during the late stage of infectious cycle. Indirect immunofluorescence assay indicated CHA down-regulated the NP protein expression. The inhibition of neuraminidase activity confirmed CHA blocked release of newly formed virus particles from infected cells. Intravenous injection of 100 mg/kg/d CHA possessed effective antiviral activity in mice, conferring 60% and 50% protection from death against H1N1 and H3N2, reducing virus titres and alleviating inflammation in the lungs effectively. These results demonstrate that CHA acts as a neuraminidase blocker to inhibit influenza A virus both in cellular and animal models. Thus, CHA has potential utility in the treatment of the influenza virus infection. PMID:28393840

  8. In vitro antiviral activity of favipiravir (T-705) against drug-resistant influenza and 2009 A(H1N1) viruses.

    Science.gov (United States)

    Sleeman, Katrina; Mishin, Vasiliy P; Deyde, Varough M; Furuta, Yousuke; Klimov, Alexander I; Gubareva, Larisa V

    2010-06-01

    Favipiravir (T-705) has previously been shown to have a potent antiviral effect against influenza virus and some other RNA viruses in both cell culture and in animal models. Currently, favipiravir is undergoing clinical evaluation for the treatment of influenza A and B virus infections. In this study, favipiravir was evaluated in vitro for its ability to inhibit the replication of a representative panel of seasonal influenza viruses, the 2009 A(H1N1) strains, and animal viruses with pandemic (pdm) potential (swine triple reassortants, H2N2, H4N2, avian H7N2, and avian H5N1), including viruses which are resistant to the currently licensed anti-influenza drugs. All viruses were tested in a plaque reduction assay with MDCK cells, and a subset was also tested in both yield reduction and focus inhibition (FI) assays. For the majority of viruses tested, favipiravir significantly inhibited plaque formation at 3.2 muM (0.5 microg/ml) (50% effective concentrations [EC(50)s] of 0.19 to 22.48 muM and 0.03 to 3.53 microg/ml), and for all viruses, with the exception of a single dually resistant 2009 A(H1N1) virus, complete inhibition of plaque formation was seen at 3.2 muM (0.5 microg/ml). Due to the 2009 pandemic and increased drug resistance in circulating seasonal influenza viruses, there is an urgent need for new drugs which target influenza. This study demonstrates that favipiravir inhibits in vitro replication of a wide range of influenza viruses, including those resistant to currently available drugs.

  9. Sequence-based identification and characterization of nosocomial influenza A(H1N1)pdm09 virus infections

    NARCIS (Netherlands)

    Jonges, M.; Rahamat-Langendoen, J.; Meijer, A.; Niesters, H. G.; Koopmans, M.

    2012-01-01

    Background: Highly transmissible viruses such as influenza are a potential source of nosocomial infections and thereby cause increased patient morbidity and mortality. Aim: To assess whether influenza virus sequence data can be used to link nosocomial influenza transmission between individuals. Meth

  10. Serologic evidence of influenza A(H1N1)pdm09 virus in northern sea otters

    Science.gov (United States)

    Li, Zhu-Nan; Ip, Hon S.; Frost, Jessica F.; White, C. LeAnn; Murray, Michael J.; Carney, Paul J.; Sun, Xiang-Jie; Stevens, James; Levine, Min Z.; Katz, Jacqueline M.

    2014-01-01

    Sporadic epizootics of pneumonia among marine mammals have been associated with multiple animal-origin influenza A virus subtypes (1–6); seals are the only known nonhuman host for influenza B viruses (7). Recently, we reported serologic evidence of influenza A virus infection in free-ranging northern sea otters (Enhydra lutris kenyoni) captured off the coast of Washington, USA, in August 2011 (8). To investigate further which influenza A virus subtype infected these otters, we tested serum samples from these otters by ELISA for antibody-binding activity against 12 recombinant hemagglutinins (rHAs) from 7 influenza A hemagglutinin (HA) subtypes and 2 lineages of influenza B virus (Technical Appendix Table 1). Estimated ages for the otters were 2–19 years (Technical Appendix Table 2); we also tested archived serum samples from sea otters of similar ages collected from a study conducted during 2001–2002 along the Washington coast (9).

  11. 2009年新型甲型H1N1流感病毒的进化趋势及未来防控中应考虑的问题%Evolutionary trend of the novel A/H1N1 influenza virus in 2009 and the major problems concerning prevention and control of this pandemic

    Institute of Scientific and Technical Information of China (English)

    曹广文

    2009-01-01

    2009年流行的新型甲型H1N1流感病毒的8个功能基因各自有一定的进化特点,其主要免疫原性基因--血凝素(HA)基因源于北美猪流感病毒.2005年在美国衣阿华(Iowa)州分离的感染人的猪H1N1的HA基因、病毒聚合酶(PB2、PBl和PA)基因、核蛋白基因(NP)和非结构基因(NS)与此次新型甲型HlNl病毒高度同源(同源性超过90%),可能是此次新型甲型H1N1病毒进化过程中的中间步骤.神经氨酸酶(NA)基因源于欧洲H1N1猪流感病毒,基质蛋白(M1和M2)基因来自欧洲H3N2亚型猪流感病毒,两段基因可能在猪体内与Iowa株发生重排而进化成此次新型甲型H1N1病毒.本文分析了新型甲型H1N1流感病毒可能的进化过程,并提出了未来防控工作中需要注意的几个科学问题.%Objective Eight functional fragments of the novel A/H1N1 influenza pandemic virus in 2009 had their own evolutionary characteristics. Among them, the hemagglutinin (HA), the major antigenic gene, was originated from swine influenza virus epidemics in North America. The HA gene, polymerase genes (PB2, PB1 and PA), nucleoprotein gene (NP) and nonstructural protein gene (NS) of the virus strain isolated in Iowa of US in 2005 shared close homology (identities more than 90%) with the corresponding sequences of the novel A/H1N1 influenza pandemic virus in 2009. The Iowa strain might be an intermediate step of the evolutionary process of this novel A/H1N1 influenza virus. The evolutionary process of the novel A/H1N1 influenza might be realized in pigs re-assorted with the neuraminidase (NA) gene from European swine H1N1 influenza virus and matrix proteins (M1 and M2) genes from European H3N2 swine influenza virus. The present paper presented possible evolutionary processes of the novel A/H1N1 influenza pandemic virus in 2009, and pointed out several relevant scientific points which should be emphasized in the prevention and control of the epidemics of the novel A/H1N1 influenza in

  12. 2009年新型甲型H1N1流感病毒血凝素基因进化及变异特征分析%Genetic evolution and variation of hemagglutinin gene of the novel A/H1N1 influenza pandemic virus in 2009

    Institute of Scientific and Technical Information of China (English)

    李淑华; 韩一芳; 谢佳新; 韩磊; 苏彤; 鹿文英; 曹广文

    2009-01-01

    目的 了解自2009年3月新型甲型H1N1流感流行以来,其主要免疫原件基因-HA基因的进化及氨基酸变异特性.方法 从NCBI下载2009年新型甲型H1N1流感病毒以及北美地区、欧洲地区、亚洲地区以往流行的甲型H1N1流感病毒HA基因序列,利用MEGA 4.0软件对所选序列进行基因进化系统发育树分析;对2009年新型甲型H1N1流感病毒HA基因的核苷酸同源性及氨基酸特异性进行分析,并与北美地区、欧洲地区、亚洲地区分离株进行比较.结果 2009年新型甲型HlNl流感病毒HA基因与2006-2007年美国A/swine/H1N1流感病毒同源性最高,核苷酸序列差异为0%~0.8%;与美国各州1930-2007年分离的A/swine/H1N1流感病毒具有明显的时间上的进化关系;与欧洲及亚洲地区A/swine/H1N1流感病毒进化无关.其重要的抗原性位点与A/human/H1N1流感病毒及流感疫苗株存在较大差异.全球流行半年多以来该病毒株没有发生明显变异.结论 2009年新型甲型H1N1流感病毒HA基因是北美A/swine/H1N1流感病毒长期进化的结果,目前尚未发现明显抗原位点的变异.%Objective To elucidate the characteristics of genetic evolution and variation trend of hemagglutinin ( HA). a major antigenic gene of the novel A/H1N1 influenza pandemic virus in 2009. Methods HA gene sequences of the novel A/H1N1 influenza pandemic virus in 2009, as well as that of the A/H1N1 influenza virus spread in North America, Europe and Asia, were downloaded from NCBI database. MEGA4.0 software was used to analyze the constructed phylogenetic tree of the selected sequences of HA gene. The nucleotide homology and amino acid specificity of the novel A/H1N1 influenza pandemic virus in 2009 were analyzed and compared with those in North America, Europe and Asia regions. Results HA gene of the novel A/H1N1 influenza pandemic virus in 2009 showed a highest homology (93. 2%-93. 4%) with the corresponding sequences of A/swine/H1N1 influenza

  13. Diverse antigenic site targeting of influenza hemagglutinin in the murine antibody recall response to A(H1N1)pdm09 virus.

    Science.gov (United States)

    Wilson, Jason R; Guo, Zhu; Tzeng, Wen-Pin; Garten, Rebecca J; Xiyan, Xu; Blanchard, Elisabeth G; Blanchfield, Kristy; Stevens, James; Katz, Jacqueline M; York, Ian A

    2015-11-01

    Here we define the epitopes on HA that are targeted by a group of 9 recombinant monoclonal antibodies (rmAbs) isolated from memory B cells of mice, immunized by infection with A(H1N1)pdm09 virus followed by a seasonal TIV boost. These rmAbs were all reactive against the HA1 region of HA, but display 7 distinct binding footprints, targeting each of the 4 known antigenic sites. Although the rmAbs were not broadly cross-reactive, a group showed subtype-specific cross-reactivity with the HA of A/South Carolina/1/18. Screening these rmAbs with a panel of human A(H1N1)pdm09 virus isolates indicated that naturally-occurring changes in HA could reduce rmAb binding, HI activity, and/or virus neutralization activity by rmAb, without showing changes in recognition by polyclonal antiserum. In some instances, virus neutralization was lost while both ELISA binding and HI activity were retained, demonstrating a discordance between the two serological assays traditionally used to detect antigenic drift.

  14. Establishment of oligonucleotide microarray for detection of influenza virus subtypes H1N1 and H3N2%H1N1和H3N2亚型流感病毒基因芯片检测方法的建立

    Institute of Scientific and Technical Information of China (English)

    王慧煜; 梅琳; 侯义宏; 李全芬; 林祥梅; 韩雪清

    2011-01-01

    为建立同时能鉴别甲型H1N1和猪流感病毒常见亚型的新型基因芯片检测方法,根据GenBank中已发表的甲型流感病毒MP的基因序列和甲型H1N1(2009)和猪流感病毒H1N1、H3N2亚型的基因序列,设计、筛选并合成7对特异性引物和1对通用引物;根据扩增的靶序列,设计并合成14条特异性探针和3条质控探针,制备了甲型H1N1(2009)流感病毒和猪流感病毒H1N1、H3N2亚型基因芯片;并进行了特异性试验、敏感性试验和田间样品的检测。结果显示,该芯片检测方法与猪细小病毒(PPV)、猪瘟病毒(CSFV)、猪繁殖与呼吸综合征病毒(PRRSV)等猪常见病毒无交叉反应;对猪H1N1、猪H3N2和甲型H1N1(2009)流感病毒而言,最低可检测到105、104和105稀释的病毒株。结果证实,该方法特异性强、敏感性高,是一种高通量的甲型H1N1和猪流感常见亚型筛查方法。%Seven pairs of primers specific for different subtypes and a pair of universal primers were carefully designed based on the genomic sequences of A/H1N1 and swine influenza virus retrieved from GenBank database.Several multiplex RT-PCR methods were then developed.Further 14 oligonucleotide probes specific for A/H1N1 and swine influenza virus were designed according to the published gene in target cDNA domains.Then a microarray for A/H1N1 and swine influenza virus was developed with its specificity and sensitivity validated by using swine influenza virus strains and samples from different areas.The results showed that all the subtypes of swine influenza virus and A/H1N1 virus could be identified simultaneously on this microarray with high sensitivity,which could reach to 105 dilute viruses.Furthermore,there was no cross reactions with PPV,CSFV and PRRSV.Therefore the microarray is a useful diagnostic method with high specificity and sensitivity,and could be used for A/H1N1 and swine influenza surveillance.

  15. Reassortment and mutations associated with emergence and spread of oseltamivir-resistant seasonal influenza A/H1N1 viruses in 2005-2009.

    Directory of Open Access Journals (Sweden)

    Ji-Rong Yang

    Full Text Available A dramatic increase in the frequency of the H275Y mutation in the neuraminidase (NA, conferring resistance to oseltamivir, has been detected in human seasonal influenza A/H1N1 viruses since the influenza season of 2007-2008. The resistant viruses emerged in the ratio of 14.3% and quickly reached 100% in Taiwan from September to December 2008. To explore the mechanisms responsible for emergence and spread of the resistant viruses, we analyzed the complete genome sequences of 25 viruses collected during 2005-2009 in Taiwan, which were chosen from various clade viruses, 1, 2A, 2B-1, 2B-2, 2C-1 and 2C-2 by the classification of hemagglutinin (HA sequences. Our data revealed that the dominant variant, clade 2B-1, in the 2007-2008 influenza emerged through an intra-subtype 4+4 reassortment between clade 1 and 2 viruses. The dominant variant acquired additional substitutions, including A206T in HA, H275Y and D354G in NA, L30R and H41P in PB1-F2, and V411I and P453S in basic polymerase 2 (PB2 proteins and subsequently caused the 2008-2009 influenza epidemic in Taiwan, accompanying the widespread oseltamivir-resistant viruses. We also characterized another 3+5 reassortant virus which became double resistant to oseltamivir and amantadine. Comparison of oseltamivir-resistant influenza A/H1N1 viruses belonging to various clades in our study highlighted that both reassortment and mutations were associated with emergence and spread of these viruses and the specific mutation, H275Y, conferring to antiviral resistance, was acquired in a hitch-hiking mechanism during the viral evolutionary processes.

  16. Generation of Live Attenuated Novel Influenza Virus A/California/7/09 (H1N1) Vaccines with High Yield in Embryonated Chicken Eggs ▿

    Science.gov (United States)

    Chen, Zhongying; Wang, Weijia; Zhou, Helen; Suguitan, Amorsolo L.; Shambaugh, Cindy; Kim, Lomi; Zhao, Jackie; Kemble, George; Jin, Hong

    2010-01-01

    Several live attenuated influenza virus A/California/7/09 (H1N1) (CA09) candidate vaccine variants that possess the hemagglutinin (HA) and neuraminidase (NA) gene segments from the CA09 virus and six internal protein gene segments from the cold-adapted influenza virus A/Ann Arbor/6/60 (H2N2) virus were generated by reverse genetics. The reassortant viruses replicated relatively poorly in embryonated chicken eggs. To improve virus growth in eggs, reassortants expressing the HA and NA of CA09 were passaged in MDCK cells and variants exhibiting large-plaque morphology were isolated. These variants replicated at levels approximately 10-fold higher than the rate of replication of the parental strains in embryonated chicken eggs. Sequence analysis indicated that single amino acid changes at positions 119, 153, 154, and 186 were responsible for the improved growth properties in MDCK cells and eggs. In addition, the introduction of a mutation at residue 155 that was previously shown to enhance the replication of a 1976 swine influenza virus also significantly improved the replication of the CA09 virus in eggs. Each variant was further evaluated for receptor binding preference, antigenicity, attenuation phenotype, and immunogenicity. Mutations at residues 153, 154, and 155 drastically reduced viral antigenicity, which made these mutants unsuitable as vaccine candidates. However, changes at residues 119 and 186 did not affect virus antigenicity or immunogenicity, justifying their inclusion in live attenuated vaccine candidates to protect against the currently circulating 2009 swine origin H1N1 viruses. PMID:19864389

  17. Generation of live attenuated novel influenza virus A/California/7/09 (H1N1) vaccines with high yield in embryonated chicken eggs.

    Science.gov (United States)

    Chen, Zhongying; Wang, Weijia; Zhou, Helen; Suguitan, Amorsolo L; Shambaugh, Cindy; Kim, Lomi; Zhao, Jackie; Kemble, George; Jin, Hong

    2010-01-01

    Several live attenuated influenza virus A/California/7/09 (H1N1) (CA09) candidate vaccine variants that possess the hemagglutinin (HA) and neuraminidase (NA) gene segments from the CA09 virus and six internal protein gene segments from the cold-adapted influenza virus A/Ann Arbor/6/60 (H2N2) virus were generated by reverse genetics. The reassortant viruses replicated relatively poorly in embryonated chicken eggs. To improve virus growth in eggs, reassortants expressing the HA and NA of CA09 were passaged in MDCK cells and variants exhibiting large-plaque morphology were isolated. These variants replicated at levels approximately 10-fold higher than the rate of replication of the parental strains in embryonated chicken eggs. Sequence analysis indicated that single amino acid changes at positions 119, 153, 154, and 186 were responsible for the improved growth properties in MDCK cells and eggs. In addition, the introduction of a mutation at residue 155 that was previously shown to enhance the replication of a 1976 swine influenza virus also significantly improved the replication of the CA09 virus in eggs. Each variant was further evaluated for receptor binding preference, antigenicity, attenuation phenotype, and immunogenicity. Mutations at residues 153, 154, and 155 drastically reduced viral antigenicity, which made these mutants unsuitable as vaccine candidates. However, changes at residues 119 and 186 did not affect virus antigenicity or immunogenicity, justifying their inclusion in live attenuated vaccine candidates to protect against the currently circulating 2009 swine origin H1N1 viruses.

  18. Hemagglutinin 222D/G polymorphism facilitates fast intra-host evolution of pandemic (H1N1 2009 influenza A viruses.

    Directory of Open Access Journals (Sweden)

    Nora Seidel

    Full Text Available The amino acid substitution of aspartic acid to glycine in hemagglutinin (HA in position 222 (HA-D222G as well as HA-222D/G polymorphism of pandemic (H1N1 2009 influenza viruses (A(H1N1pdm09 were frequently reported in severe influenza in humans and mice. Their impact on viral pathogenicity and the course of influenza has been discussed controversially and the underlying mechanism remained unclarified. In the present study, BALB/c mice, infected with the once mouse lung- and cell-passaged A(H1N1pdm09 isolate A/Jena/5258/09 (mpJena/5258, developed severe pneumonia. From day 2 to 3 or 4 post infection (p.i. symptoms (body weight loss and clinical score continuously worsened. After a short disease stagnation or even recovery phase in most mice, severity of disease further increased on days 6 and 7 p.i. Thereafter, surviving mice recovered. A 45 times higher virus titer maximum in the lung than in the trachea on day 2 p.i. and significantly higher tracheal virus titers compared to lung on day 6 p.i. indicated changes in the organ tropism during infection. Sequence analysis revealed an HA-222D/G polymorphism. HA-D222 and HA-G222 variants co-circulated in lung and trachea. Whereas, HA-D222 variant predominated in the lung, HA-G222 became the major variant in the trachea after day 4 p.i. This was accompanied by lower neutralizing antibody titers and broader receptor recognition including terminal sialic acid α-2,3-linked galactose, which is abundant on mouse trachea epithelial cells. Plaque-purified HA-G222-mpJena/5258 virus induced severe influenza with maximum symptom on day 6 p.i. These results demonstrated for the first time that HA-222D/G quasispecies of A(H1N1pdm09 caused severe biphasic influenza because of fast viral intra-host evolution, which enabled partial antibody escape and minor changes in receptor binding.

  19. Punctuated Evolution of Influenza Virus Neuraminidase (A/H1N1 under Opposing Migration and Vaccination Pressures

    Directory of Open Access Journals (Sweden)

    J. C. Phillips

    2014-01-01

    Full Text Available Influenza virus contains two highly variable envelope glycoproteins, hemagglutinin (HA and neuraminidase (NA. The structure and properties of HA, which is responsible for binding the virus to the cell that is being infected, change significantly when the virus is transmitted from avian or swine species to humans. Here we focus first on the simpler problem of the much smaller human individual evolutionary amino acid mutational changes in NA, which cleaves sialic acid groups and is required for influenza virus replication. Our thermodynamic panorama shows that very small amino acid changes can be monitored very accurately across many historic (1945–2011 Uniprot and NCBI strains using hydropathicity scales to quantify the roughness of water film packages. Quantitative sequential analysis is most effective with the fractal differential hydropathicity scale based on protein self-organized criticality (SOC. Our analysis shows that large-scale vaccination programs have been responsible for a very large convergent reduction in common influenza severity in the last century. Hydropathic analysis is capable of interpreting and even predicting trends of functional changes in mutation prolific viruses directly from amino acid sequences alone. An engineered strain of NA1 is described which could well be significantly less virulent than current circulating strains.

  20. Prevalence of influenza A and variation of H1N1 influenza A virus in Shanghai area in 2009%2009年上海地区甲型流行性感冒流行及甲型H1N1病毒分离株变异分析

    Institute of Scientific and Technical Information of China (English)

    吕锡宏; 谈逸云; 居丽雯; 申惠国; 高颖阳; 熊海燕; 姜庆五

    2010-01-01

    Objective To understand epidemic characteristics of human influenza A and the genetic and antigenic variations of H1N1 influenza A isolates in Shanghai area in 2009. Methods Throat swabs were collected from patients with influenza-like illness in the sentinel surveillance clinic in Shanghai area in 2009, then inoculated in Madin-Darby canine kidney (MDCK) cell lines. The types of influenza were identified by direct immunofluorescence assay (DIF) and the subtypes were determined by reverse transcriptase-polymerase chain reaction (RT-PCR). Segments of hemagglutinin (HA) and neuraminidase (NA) genes of some 2009 H1N1 influenza A isolates were amplified and sequenced. HA and NA gene mutations of 2009 H1N1 influenza A isolates were analyzed. Results Seasonal H1N1 and H3N2 influenza A viruses co-circulated during the spring of 2009 in Shanghai area. Seasonal H3N2 began to co-circulate with 2009 H1N1 in August (the 32nd week) and finally2009 H1N1 became dominate since the 40th week. The phylogenetic tree of 2009 H1N1 HA segment revealed that the isolates from different regions and months were interspersed with each other, but all were clustered into one branch which closed to strains in Spain, Russia, Denmark and other European countries. Mutations were found in some HA amino acid sites, but none of them was in the antigenic determinant region. No change was observed in the 274 NA amino acid residues which were related to the drug resistance to oseltamivir. PB2 protein analysis showed that the 627 and 701 amino acid residues were glutamic acid and aspartic acid respectively, which were the same encoded amino acid with avian flu PB2 protein. Conclusions Seasonal H1N1 and H3N2 co-circulated in the spring of 2009, then both 2009 H1N1 and seasonal H3N2 were prevalent in Summer and Autumn, and 2009 H1N1 finally became dominate in Autumn. Compared to early 2009 H1N1 strains, variations are detected in H1N1 influenza A viruses, but none of them has epidemiological influence, and

  1. Systems-level comparison of host-responses elicited by avian H5N1 and seasonal H1N1 influenza viruses in primary human macrophages.

    Science.gov (United States)

    Lee, Suki M Y; Gardy, Jennifer L; Cheung, C Y; Cheung, Timothy K W; Hui, Kenrie P Y; Ip, Nancy Y; Guan, Y; Hancock, Robert E W; Peiris, J S Malik

    2009-12-14

    Human disease caused by highly pathogenic avian influenza (HPAI) H5N1 can lead to a rapidly progressive viral pneumonia leading to acute respiratory distress syndrome. There is increasing evidence from clinical, animal models and in vitro data, which suggests a role for virus-induced cytokine dysregulation in contributing to the pathogenesis of human H5N1 disease. The key target cells for the virus in the lung are the alveolar epithelium and alveolar macrophages, and we have shown that, compared to seasonal human influenza viruses, equivalent infecting doses of H5N1 viruses markedly up-regulate pro-inflammatory cytokines in both primary cell types in vitro. Whether this H5N1-induced dysregulation of host responses is driven by qualitative (i.e activation of unique host pathways in response to H5N1) or quantitative differences between seasonal influenza viruses is unclear. Here we used microarrays to analyze and compare the gene expression profiles in primary human macrophages at 1, 3, and 6 h after infection with H5N1 virus or low-pathogenic seasonal influenza A (H1N1) virus. We found that host responses to both viruses are qualitatively similar with the activation of nearly identical biological processes and pathways. However, in comparison to seasonal H1N1 virus, H5N1 infection elicits a quantitatively stronger host inflammatory response including type I interferon (IFN) and tumor necrosis factor (TNF)-alpha genes. A network-based analysis suggests that the synergy between IFN-beta and TNF-alpha results in an enhanced and sustained IFN and pro-inflammatory cytokine response at the early stage of viral infection that may contribute to the viral pathogenesis and this is of relevance to the design of novel therapeutic strategies for H5N1 induced respiratory disease.

  2. Systems-level comparison of host-responses elicited by avian H5N1 and seasonal H1N1 influenza viruses in primary human macrophages.

    Directory of Open Access Journals (Sweden)

    Suki M Y Lee

    Full Text Available Human disease caused by highly pathogenic avian influenza (HPAI H5N1 can lead to a rapidly progressive viral pneumonia leading to acute respiratory distress syndrome. There is increasing evidence from clinical, animal models and in vitro data, which suggests a role for virus-induced cytokine dysregulation in contributing to the pathogenesis of human H5N1 disease. The key target cells for the virus in the lung are the alveolar epithelium and alveolar macrophages, and we have shown that, compared to seasonal human influenza viruses, equivalent infecting doses of H5N1 viruses markedly up-regulate pro-inflammatory cytokines in both primary cell types in vitro. Whether this H5N1-induced dysregulation of host responses is driven by qualitative (i.e activation of unique host pathways in response to H5N1 or quantitative differences between seasonal influenza viruses is unclear. Here we used microarrays to analyze and compare the gene expression profiles in primary human macrophages at 1, 3, and 6 h after infection with H5N1 virus or low-pathogenic seasonal influenza A (H1N1 virus. We found that host responses to both viruses are qualitatively similar with the activation of nearly identical biological processes and pathways. However, in comparison to seasonal H1N1 virus, H5N1 infection elicits a quantitatively stronger host inflammatory response including type I interferon (IFN and tumor necrosis factor (TNF-alpha genes. A network-based analysis suggests that the synergy between IFN-beta and TNF-alpha results in an enhanced and sustained IFN and pro-inflammatory cytokine response at the early stage of viral infection that may contribute to the viral pathogenesis and this is of relevance to the design of novel therapeutic strategies for H5N1 induced respiratory disease.

  3. Antiviral activity of Basidiomycete mycelia against influenza type A(serotype H1N1) and herpes simplex virus type 2 in cell culture

    Institute of Scientific and Technical Information of China (English)

    Tetiana; Krupodorova; Svetlana; Rybalko; Victor; Barshteyn

    2014-01-01

    In this study, we investigated the in vitro antiviral activity of the mycelia of higher mushrooms against influenza virus type A(serotype H1N1) and herpes simplex virus type 2(HSV-2), strain BH. All 10 investigated mushroom species inhibited the reproduction of influenza virus strain A/FM/1/47(H1N1) in MDCK cells reducing the infectious titer by 2.0–6.0 lg ID50. Four species, Pleurotus ostreatus, Fomes fomentarius, Auriporia aurea, and Trametes versicolor, were also determined to be effective against HSV-2 strain BH in RK-13 cells, with similar levels of inhibition as for influenza. For some of the investigated mushroom species—Pleurotus eryngii, Lyophyllum shimeji, and Flammulina velutipes—this is the first report of an anti-influenza effect. This study also reports the first data on the medicinal properties of A. aurea, including anti-influenza and antiherpetic activities. T. versicolor 353 mycelium was found to have a high therapeutic index(324.67), and may be a promising material for the pharmaceutical industry as an anti-influenza and antiherpetic agent with low toxicity. Mycelia with antiviral activity were obtained in our investigation by bioconversion of agricultural wastes(amaranth flour after CO2 extraction), which would reduce the cost of the final product and solve some ecological problems.

  4. Antiviral activity of Basidiomycete mycelia against influenza type A (serotype H1N1) and herpes simplex virus type 2 in cell culture.

    Science.gov (United States)

    Krupodorova, Tetiana; Rybalko, Svetlana; Barshteyn, Victor

    2014-10-01

    In this study, we investigated the in vitro antiviral activity of the mycelia of higher mushrooms against influenza virus type A (serotype H1N1) and herpes simplex virus type 2 (HSV-2), strain BH. All 10 investigated mushroom species inhibited the reproduction of influenza virus strain A/FM/1/47 (H1N1) in MDCK cells reducing the infectious titer by 2.0-6.0 lg ID50. Four species, Pleurotus ostreatus, Fomes fomentarius, Auriporia aurea, and Trametes versicolor, were also determined to be effective against HSV-2 strain BH in RK-13 cells, with similar levels of inhibition as for influenza. For some of the investigated mushroom species-Pleurotus eryngii, Lyophyllum shimeji, and Flammulina velutipes-this is the first report of an anti-influenza effect. This study also reports the first data on the medicinal properties of A. aurea, including anti-influenza and antiherpetic activities. T. versicolor 353 mycelium was found to have a high therapeutic index (324.67), and may be a promising material for the pharmaceutical industry as an anti-influenza and antiherpetic agent with low toxicity. Mycelia with antiviral activity were obtained in our investigation by bioconversion of agricultural wastes (amaranth flour after CO2 extraction), which would reduce the cost of the final product and solve some ecological problems.

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

    Energy Technology Data Exchange (ETDEWEB)

    Wörmann, Xenia [Department of Molecular Biology, Max Planck Institute for Infection Biology, Berlin (Germany); Lesch, Markus [Department of Molecular Biology, Max Planck Institute for Infection Biology, Berlin (Germany); Steinbeis Innovation gGmbH, Center for Systems Biomedicine, Falkensee (Germany); Welke, Robert-William [Department of Biology, Molecular Biophysics, IRI Life Sciences, Humboldt-Universität zu Berlin (Germany); Okonechnikov, Konstantin; Abdurishid, Mirshat [Department of Molecular Biology, Max Planck Institute for Infection Biology, Berlin (Germany); Sieben, Christian [Department of Biology, Molecular Biophysics, IRI Life Sciences, Humboldt-Universität zu Berlin (Germany); Geissner, Andreas [Department for Biomolecular Systems, Max Planck Institute for Colloids and Interfaces, Potsdam (Germany); Institute of Chemistry and Biochemistry, Free University, Berlin (Germany); Brinkmann, Volker [Department of Molecular Biology, Max Planck Institute for Infection Biology, Berlin (Germany); Kastner, Markus [Institute for Biophysics, Johannes Kepler University, Linz (Austria); Karner, Andreas [Center for Advanced Bioanalysis GmbH (CBL), Linz (Austria); Zhu, Rong; Hinterdorfer, Peter [Institute for Biophysics, Johannes Kepler University, Linz (Austria); Anish, Chakkumkal [Department for Biomolecular Systems, Max Planck Institute for Colloids and Interfaces, Potsdam (Germany); Seeberger, Peter H. [Department for Biomolecular Systems, Max Planck Institute for Colloids and Interfaces, Potsdam (Germany); Institute of Chemistry and Biochemistry, Free University, Berlin (Germany); Herrmann, Andreas [Department of Biology, Molecular Biophysics, IRI Life Sciences, Humboldt-Universität zu Berlin (Germany); and others

    2016-05-15

    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 (HA{sub 1} D130E, HA{sub 2} 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. - Highlights: • We observed a spontaneous mutation of a 2009-pandemic H1N1 influenza virus in vitro. • The adaptation led to a 100-fold rise in replication rate in human A549 cells. • Adaptation was caused by two mutations in the HA gene segment. • Adaptation correlates with increased fusion pH and decreased receptor affinity.

  6. Alteration of protein levels during influenza virus H1N1 infection in host cells: a proteomic survey of host and virus reveals differential dynamics.

    Directory of Open Access Journals (Sweden)

    Susann Kummer

    Full Text Available We studied the dynamics of the proteome of influenza virus A/PR/8/34 (H1N1 infected Madin-Darby canine kidney cells up to 12 hours post infection by mass spectrometry based quantitative proteomics using the approach of stable isotope labeling by amino acids in cell culture (SILAC. We identified 1311 cell proteins and, apart from the proton channel M2, all major virus proteins. Based on their abundance two groups of virus proteins could be distinguished being in line with the function of the proteins in genesis and formation of new virions. Further, the data indicate a correlation between the amount of proteins synthesized and their previously determined copy number inside the viral particle. We employed bioinformatic approaches such as functional clustering, gene ontology, and pathway (KEGG enrichment tests to uncover co-regulated cellular protein sets, assigned the individual subsets to their biological function, and determined their interrelation within the progression of viral infection. For the first time we are able to describe dynamic changes of the cellular and, of note, the viral proteome in a time dependent manner simultaneously. Through cluster analysis, time dependent patterns of protein abundances revealed highly dynamic up- and/or down-regulation processes. Taken together our study provides strong evidence that virus infection has a major impact on the cell status at the protein level.

  7. Sublingual administration of bacteria-expressed influenza virus hemagglutinin 1 (HA1) induces protection against infection with 2009 pandemic H1N1 influenza virus.

    Science.gov (United States)

    Shim, Byoung-Shik; Choi, Jung-Ah; Song, Ho-Hyun; Park, Sung-Moo; Cheon, In Su; Jang, Ji-Eun; Woo, Sun Je; Cho, Chung Hwan; Song, Min-Suk; Kim, Hyemi; Song, Kyung Joo; Lee, Jae Myun; Kim, Suhng Wook; Song, Dae Sub; Choi, Young Ki; Kim, Jae-Ouk; Nguyen, Huan Huu; Kim, Dong Wook; Bahk, Young Yil; Yun, Cheol-Heui; Song, Man Ki

    2013-02-01

    Influenza viruses are respiratory pathogens that continue to pose a significantly high risk of morbidity and mortality of humans worldwide. Vaccination is one of the most effective strategies for minimizing damages by influenza outbreaks. In addition, rapid development and production of efficient vaccine with convenient administration is required in case of influenza pandemic. In this study, we generated recombinant influenza virus hemagglutinin protein 1 (sHA1) of 2009 pandemic influenza virus as a vaccine candidate using a well-established bacterial expression system and administered it into mice via sublingual (s.l.) route. We found that s.l. immunization with the recombinant sHA1 plus cholera toxin (CT) induced mucosal antibodies as well as systemic antibodies including neutralizing Abs and provided complete protection against infection with pandemic influenza virus A/CA/04/09 (H1N1) in mice. Indeed, the protection efficacy was comparable with that induced by intramuscular (i.m.) immunization route utilized as general administration route of influenza vaccine. These results suggest that s.l. vaccination with the recombinant non-glycosylated HA1 protein offers an alternative strategy to control influenza outbreaks including pandemics.

  8. The association between serum biomarkers and disease outcome in influenza A(H1N1pdm09 virus infection: results of two international observational cohort studies.

    Directory of Open Access Journals (Sweden)

    Richard T Davey

    Full Text Available BACKGROUND: Prospective studies establishing the temporal relationship between the degree of inflammation and human influenza disease progression are scarce. To assess predictors of disease progression among patients with influenza A(H1N1pdm09 infection, 25 inflammatory biomarkers measured at enrollment were analyzed in two international observational cohort studies. METHODS: Among patients with RT-PCR-confirmed influenza A(H1N1pdm09 virus infection, odds ratios (ORs estimated by logistic regression were used to summarize the associations of biomarkers measured at enrollment with worsened disease outcome or death after 14 days of follow-up for those seeking outpatient care (FLU 002 or after 60 days for those hospitalized with influenza complications (FLU 003. Biomarkers that were significantly associated with progression in both studies (p<0.05 or only in one (p<0.002 after Bonferroni correction were identified. RESULTS: In FLU 002 28/528 (5.3% outpatients had influenza A(H1N1pdm09 virus infection that progressed to a study endpoint of complications, hospitalization or death, whereas in FLU 003 28/170 (16.5% inpatients enrolled from the general ward and 21/39 (53.8% inpatients enrolled directly from the ICU experienced disease progression. Higher levels of 12 of the 25 markers were significantly associated with subsequent disease progression. Of these, 7 markers (IL-6, CD163, IL-10, LBP, IL-2, MCP-1, and IP-10, all with ORs for the 3(rd versus 1(st tertile of 2.5 or greater, were significant (p<0.05 in both outpatients and inpatients. In contrast, five markers (sICAM-1, IL-8, TNF-α, D-dimer, and sVCAM-1, all with ORs for the 3(rd versus 1(st tertile greater than 3.2, were significantly (p≤.002 associated with disease progression among hospitalized patients only. CONCLUSIONS: In patients presenting with varying severities of influenza A(H1N1pdm09 virus infection, a baseline elevation in several biomarkers associated with inflammation

  9. Burden of pediatric influenza A virus infection post swine-flu H1N1 pandemic in Egypt

    Institute of Scientific and Technical Information of China (English)

    Adel Khattab; Malak Shaheen; Terez Kamel; Amel El Faramay; Safaa Abd El Rahman; Dalia Nabil; Mohamed Gouda

    2013-01-01

    Objective:To screen children with influenza like illness or with symptoms of acute respiratory tract infections for influenza A virus infection—post swine flu pandemic era—using rapid influenza diagnostic tests. Methods:During two years (2010&2011), 1 200 children with influenza like illness or acute respiratory tract infections (according to World Health Organization criteria) were recruited. Their ages ranged from 2-60 months. Nasopharyngeal aspirates specimens were collected from all children for rapid influenza A diagnostic test. Results: Influenza A virus rapid test was positive in 47.5%of the children;the majority (89.6%) were presented with lower respiratory tract infections. Respiratory rate and temperature were significantly higher among positive rapid influenza test patients. Conclusions:Influenza A virus infection is still a major cause of respiratory tract infections in Egyptian children. It should be considered in all cases with cough and febrile episodes and influenza like symptoms even post swine flu pandemic.

  10. The impact of altitude on hospitalization and hospital mortality from pandemic 2009 influenza A (H1N1 virus pneumonia in Mexico El impacto de la altitud en las tasas de hospitalización y mortalidad por el virus de la influenza A (H1N1 pandémico en México

    Directory of Open Access Journals (Sweden)

    Rogelio Pérez-Padilla

    2013-02-01

    Full Text Available OBJECTIVE: To determine the effect of altitude of residence on influenza A (H1N1. MATERIALS AND METHODS: We analyzed 207 135 officially notified of influenza-like illness (ILI cases, 23 048 hospitalizations and 573 deaths during the first months of the novel pandemic influenza A H1N1 virus, to examine if residents of high altitude had more frequently these adverse outcomes. RESULTS: Adjusted rates for hospitalization and hospital mortality rates increased with altitude, probably due to hypoxemia.OBJETIVO: Determinar el efecto de la altitud del lugar de residencia sobre la epidemia de influenza A (H1N1. MATERIAL Y MÉTODOS: Se analizaron 207 135 casos notificados a la Secretaría de Salud, 23 048 hospitalizaciones y 573 muertes por enfermedad similar a la influenza (ILI, por sus siglas en inglés durante los primeros meses de la pandemia del nuevo virus de la influenza A H1N1 durante 2009, para examinar si los residentes de zonas más altas presentaron tasas más altas de hospitalización y muerte. RESULTADOS: Las tasas ajustadas de hospitalización y mortalidad hospitalaria se incrementaron con la altitud probablemente por la presencia de hipoxemia.

  11. Observation on the adverse reactions and immunological effects in subjects received split influenza A (H1N1) virus vaccine%甲型H1N1流感裂解疫苗的接种反应及免疫效果观察

    Institute of Scientific and Technical Information of China (English)

    吴碧娇; 蔡文安

    2011-01-01

    Objective To observe the adverse reactions and immunological effects in subjects received split influenza A (H1N1) virus vaccine. Methods A total of 43,648 healthy subjects of different groups were immunized with the split influenza A (H1N1) virus vaccine and the adverse reactions and incidence of influenza A (H1N1) were surveyed six onths after vaccination. Results No serious adverse events were occurred to the persons received the vaccine. There 86 persons with the symptoms of cough accompanied with fever and throat pain were randomly sampled for detection of influenza A (H1N1) virus nucleic acid and the results were all negative. Conclusion The split A (H1N1) influenza vaccine demonstrated a good safety and immunological effects.%目的 观察甲型H1N1流感裂解疫苗接种反应及其免疫效果.方法对不同组别的健康人群43 648人进行免疫接种,观察接种反应及完成接种后6个月内甲型H1N1流感发病情况.结果 所有接种对象均未发生即时反应和严重异常反应,出现疑似预防接种异常反应以一般反应为主,未有出现异常和全身强副反应;完成免疫接种后6个月内随机抽查出现发热伴咳嗽、咽痛等症状86人检测甲型H1N1流感病毒核酸均为阴性.结论 甲型H1N1流感裂解疫苗具有良好的安全性和免疫原性.

  12. Assessment of the removal and inactivation of influenza viruses H5N1 and H1N1 by drinking water treatment.

    Science.gov (United States)

    Lénès, Dorothée; Deboosere, Nathalie; Ménard-Szczebara, Florence; Jossent, Jérôme; Alexandre, Virginie; Machinal, Claire; Vialette, Michèle

    2010-04-01

    Since 2003, there has been significant concern about the possibility of an outbreak of avian influenza virus subtype H5N1. Moreover, in the last few months, a pandemic of a novel swine-origin influenza A virus, namely A(H1N1), has already caused hundreds of thousands of human cases of illness and thousands of deaths. As those viruses could possibly contaminate water resources through wild birds excreta or through sewage, the aim of our work was to find out whether the treatment processes in use in the drinking water industry are suitable for eradicating them. The effectiveness of physical treatments (coagulation-flocculation-settling, membrane ultrafiltration and ultraviolet) was assessed on H5N1, and that of disinfectants (monochloramine, chlorine dioxide, chlorine, and ozone) was established for both the H5N1 and H1N1 viruses. Natural water samples were spiked with human H5N1/H1N1 viruses. For the coagulation-settling experiments, raw surface water was treated in jar-test pilots with 3 different coagulating agents (aluminum sulfate, ferric chloride, aluminum polychorosulfate). Membrane performance was quantified using a hollow-fiber ultrafiltration system. Ultraviolet irradiation experiments were conducted with a collimated beam that made it possible to assess the effectiveness of various UV doses (25-60 mJ/cm2). In the case of ozone, 0.5 mg/L and 1 mg/L residual concentrations were tested with a contact time of 10 min. Finally, for chlorine, chlorine dioxide and monochloramine treatments, several residual oxidant target levels were tested (from 0.3 to 3 mg/L) with contact times of 5-120 min. The infectivity of the H5N1 and H1N1 viruses in water samples was quantified in cell culture using a microtiter endpoint titration. The impact of coagulation-settling on the H5N1 subtype was quite low and variable. In contrast, ultrafiltration achieved more than a 3-log reduction (and more than a 4-log removal in most cases), and UV treatment was readily effective on its

  13. Chicken interferon alpha pretreatment reduces virus replication of pandemic H1N1 and H5N9 avian influenza viruses in lung cell cultures from different avian species

    National Research Council Canada - National Science Library

    Jiang, Haijun; Yang, Hanchun; Kapczynski, Darrell R

    2011-01-01

    .... In these studies, we assessed the protective potential of exogenous chicken IFN-α applied to chicken, duck, and turkey primary lung cell cultures prior to infection with the pandemic H1N1 virus...

  14. Surveillance of influenza viruses attacking children in Beijing during 2009 pandemic influenza A(H1N1)%2009甲型H1N1流感大流行期间北京儿童的流感监测

    Institute of Scientific and Technical Information of China (English)

    朱汝南; 沙莉; 袁艺; 王菲; 胡凤华; 李杰; 胡岚; 张宝元; 曹玲; 金丽敏; 李娟娟; 钱渊; 王晓颖; 孙宇; 王芳; 邓洁; 赵林清; 曲东; 李颖; 任晓旭

    2010-01-01

    目的 了解2009年甲型H1N1流感大流行期间北京地区儿童中流感流行的情况.方法 采用WHO推荐的实时荧光定量RT-PCR和国家流感中心推荐的分型方法,对2009年甲型H1N1流感大流行期间因流感样症状来首都儿科研究所附属儿童医院就诊患儿的咽拭子标本进行流感病毒核酸检测.结果 2009年6月1日至2010年2月28日期间共检测了4363份咽拭子标本,其中623例为甲型H1N1阳性,阳性率为14.3%,657例为其他甲型流感病毒阳性(15.1%),所有甲型流感病毒的总阳性率为29.3%.623例中有23例为危重症病例(占阳性患者的3.7%),其中5例死亡.618例信息完整的甲型H1N1病例中,患儿年龄为14天~16岁,性别比例为男比女为1.3:1.1~3岁儿童占25.2%,3~6岁学龄前儿童和6~12岁学龄儿童所占比例相近,各约占30%.在监测期间,仅呈现了一个甲型H1N1的流行波.2009年11月达到最高峰,随后减弱,2010年2月快速下降至2.7%.对监测期间每周20~30份临床标本同时进行季节性流感的监测显示,季节性H3N2、甲型H1N1和乙型流感交替流行.呼吸道合胞病毒(RSV)在甲型H1N1流行趋势减缓后逐渐流行成为流行优势株.结论 2009年6月至2010年2月北京地区儿童中出现甲型H1N1的流行,主要累及学龄前和学龄儿童.季节性流感和RSV与甲型H1N1交替流行.%Objective To investigate the prevalence of influenza virus infections in infants and young children during the pandemic period of 2009 influenza A(H1N1)in Beijing.Methods Throat swabs were collected from children visited the affiliated Children's Hospital to Capital Institute of Pediatrics for influenza-like illness from June 1,2009 to February 28,2010.The specific gene segments of 2009 pandemic influenza H1N1 and seasonal influenza viruses were amplified from samples by real-time RT-PCR recommended by WHO and National Influenza Reference Center of China.Results Out of 4363 clinical samples tested by real

  15. Un nuevo virus A/H1N1, una nueva pandemia: Influenza un riesgo permanente para una humanidad globalizada

    OpenAIRE

    2014-01-01

    La influenza es una enfermedad altamente infectocontagiosa de la cual se tienen registros históricos descriptivos desde la época griega y de certeza etiológica tan solo hace casi ocho décadas atras. Su agente causal es el virus del influenza de los que se conoce exiten tres grandes tipos: A B y C. El tipo A tiene la propiedad de circular por diversos reservorios biológicos, tales como el hombre, los cerdos y las aves, entre otros. Representa además una elevada variabilidad g...

  16. Introduction of a Novel Swine-Origin Influenza A (H1N1 Virus into Milwaukee, Wisconsin in 2009

    Directory of Open Access Journals (Sweden)

    Swati Kumar

    2009-06-01

    Full Text Available On 17 April 2009, novel swine origin influenza A virus (S-OIV cases appeared within the United States. Most influenza A diagnostic assays currently utilized in local clinical laboratories do not allow definitive subtype determination. Detailed subtype analysis of influenza A positive samples in our laboratory allowed early confirmation of a large outbreak of S-OIV in southeastern Wisconsin (SEW. The initial case of S-OIV in SEW was detected on 28 April 2009. All influenza A samples obtained during the 16 week period prior to 28 April 2009, and the first four weeks of the subsequent epidemic were sub typed. Four different multiplex assays were employed, utilizing real time PCR and end point PCR to fully subtype human and animal influenza viral components. Specific detection of S-OIV was developed within days. Data regarding patient demographics and other concurrently circulating viruses were analyzed. During the first four weeks of the epidemic, 679 of 3726 (18.2% adults and children tested for influenza A were identified with S-OIV infection. Thirteen patients (0.34% tested positive for seasonal human subtypes of influenza A during the first two weeks and none in the subsequent 2 weeks of the epidemic. Parainfluenza viruses were the most prevalent seasonal viral agents circulating during the epidemic (of those tested, with detection rates of 12% followed by influenza B and RSV at 1.9% and 0.9% respectively. S-OIV was confirmed on day 2 of instituting subtype testing and within 4 days of report of national cases of S-OIV. Novel surge capacity diagnostic infrastructure exists in many specialty and research laboratories around the world. The capacity for broader influenza A sub typing at the local laboratory level allows timely and accurate detection of novel strains as they emerge in the community, despite the presence of other circulating viruses producing identical illness. This is likely to become increasingly important given the need for

  17. The critical role of Notch ligand Delta-like 1 in the pathogenesis of influenza A virus (H1N1 infection.

    Directory of Open Access Journals (Sweden)

    Toshihiro Ito

    2011-11-01

    Full Text Available Influenza A viral infections have been identified as the etiologic agents for historic pandemics, and contribute to the annual mortality associated with acute viral pneumonia. While both innate and acquired immunity are important in combating influenza virus infection, the mechanism connecting these arms of the immune system remains unknown. Recent data have indicated that the Notch system is an important bridge between antigen-presenting cells (APCs and T cell communication circuits and plays a central role in driving the immune system to overcome disease. In the present study, we examine the role of Notch signaling during influenza H1N1 virus infection, focusing on APCs. We demonstrate here that macrophages, but not dendritic cells (DCs, increased Notch ligand Delta-like 1 (Dll1 expression following influenza virus challenge. Dll1 expression on macrophages was dependent on retinoic acid-inducible gene-I (RIG-I induced type-I IFN pathway, and not on the TLR3-TRIF pathway. We also found that IFNα-Receptor knockout mice failed to induce Dll1 expression on lung macrophages and had enhanced mortality during influenza virus infection. Our results further showed that specific neutralization of Dll1 during influenza virus challenge induced higher mortality, impaired viral clearance, and decreased levels of IFN-γ. In addition, we blocked Notch signaling by using γ-secretase inhibitor (GSI, a Notch signaling inhibitor. Intranasal administration of GSI during influenza infection also led to higher mortality, and higher virus load with excessive inflammation and an impaired production of IFN-γ in lungs. Moreover, Dll1 expression on macrophages specifically regulates IFN-γ levels from CD4(+and CD8(+T cells, which are important for anti-viral immunity. Together, the results of this study show that Dll1 positively influences the development of anti-viral immunity, and may provide mechanistic approaches for modifying and controlling the immune response

  18. Narcissus tazetta lectin shows strong inhibitory effects against respiratory syncytial virus, influenza A (H1N1, H3N2, H5N1) and B viruses

    Indian Academy of Sciences (India)

    Linda S M Ooi; Wing-Shan Ho; Karry L K Ngai; Li Tian; Paul K S Chan; Samuel S M Sun; Vincent E C Ooi

    2010-03-01

    Amannose-binding lectin (Narcissus tazetta lectin [NTL]) with potent antiviral activity was isolated and purified from the bulbs of the Chinese daffodil Narcissus tazetta var. chinensis, using ion exchange chromatography on diethylaminoethyl (DEAE)-cellulose, affinity chromatography on mannose–agarose and fast protein liquid chromatography (FPLC)-gel filtration on Superose 12. The purified lectin was shown to have an apparent molecular mass of 26 kDa by gel filtration and 13 kDa by SDS–PAGE, indicating that it is probably a dimer with two identical subunits. The cDNA-derived amino acid sequence of NTL as determined by molecular cloning also reveals that NTL protein contains a mature polypeptide consisting of 105 amino acids and a C-terminal peptide extension. Three-dimensional modelling study demonstrated that the NTL primary polypeptide contains three subdomains, each with a conserved mannose-binding site. It shows a high homology of about 60%–80% similarity with the existing monocot mannose-binding lectins. NTL could significantly inhibit plaque formation by the human respiratory syncytial virus (RSV) with an IC50 of 2.30 g/ml and exhibit strong antiviral properties against influenza A (H1N1, H3N2, H5N1) and influenza B viruses with IC50 values ranging from 0.20 g/ml to 1.33 g/ml in a dose-dependent manner. It is worth noting that the modes of antiviral action of NTL against RSV and influenza A virus are significantly different. NTL is effective in the inhibition of RSV during the whole viral infection cycle, but the antiviral activity of NTL is mainly expressed at the early stage of the viral cycle of influenza A (H1N1) virus. NTL with a high selective index (SI=CC50/IC50 ≥ 141) resulting from its potent antiviral activity and low cytotoxicity demonstrates a potential for biotechnological development as an antiviral agent.

  19. Follow-up after acute respiratory distress syndrome caused by influenza a (H1N1 virus infection

    Directory of Open Access Journals (Sweden)

    Carlos Toufen Jr.

    2011-01-01

    Full Text Available BACKGROUND: There are no reports on the long-term follow-up of patients with swine-origin influenza A virus infection that progressed to acute respiratory distress syndrome. METHODS: Four patients were prospectively followed up with pulmonary function tests and high-resolution computed tomography for six months after admission to an intensive care unit. RESULTS: Pulmonary function test results assessed two months after admission to the intensive care unit showed reduced forced vital capacity in all patients and low diffusion capacity for carbon monoxide in two patients. At six months, pulmonary function test results were available for three patients. Two patients continued to have a restrictive pattern, and none of the patients presented with abnormal diffusion capacity for carbon monoxide. All of them had a diffuse ground-glass pattern on high-resolution computed tomography that improved after six months. CONCLUSIONS: Despite the marked severity of lung disease at admission, patients with acute respiratory distress syndrome caused by swine-origin influenza A virus infection presented a late but substantial recovery over six months of follow-up.

  20. Isolation, Identification and Homology Analysis of the First Influenza A (H1N1) Virus in A District%某区甲型H1N1流感病毒分离鉴定及同源性的分析

    Institute of Scientific and Technical Information of China (English)

    曹晓; 巩飚; 胡淮洁; 许娇; 冉冉

    2014-01-01

    Objective Detection and separation of H1N1 influenza virus, the first area of Kaifeng virus strains were isolated from whole genome sequencing and homology analysis, to provide a scientific basis for the study of influenza virus epidemic and the variation law.Methods Real-time RT-PCR method for detection, screening to determine the influenza A H1N1 virus positive specimens; using MDCK cells isolated H1N1 influenza virus strain A/Kaifeng/01/2009 (H1N1); measured and analyzed their whole genome sequence; conducted using sequence alignment homology analysis.Results H1N1 influenza virus were detected in samples from 1828 were positive for influenza-like illness in 286 copies, the positive rate of 15.6%. The first time the whole strain of H1N1 influenza virus genome sequence and in Kaifeng area. Genome sequence analysis showed that: the strain and 2009 pandemic strain is highly homologous to the same evolutionary branch. Previous epidemic of swine influenza virus strains found in contrast, HA gene 12 bp point mutation occurred. Conclusion MDCK cells (H1N1) virus has a high sensitivity; Kaifeng area first case of H1N1 flu virus strains isolated in North America epidemic strains highly homologous; compared with the previous representative strains of classical swine influenza HA protein antigen appeared drift; lay the foundation for further research in molecular biology (H1N1) virus in the future.%目的:检测并分离甲型H1N1流感病毒,对开封地区首次分离到的病毒株进行全基因组序列测定及同源性分析,为研究流感病毒的流行及变异规律提供科学依据。方法采用Real-time RT-PCR方法检测,筛选确定出甲型H1N1流感病毒阳性标本;利用狗肾传代细胞分离得到甲型H1N1流感病毒株A/Kaifeng/01/2009(H1N1);测定并分析其全基因组序列;利用序列比对进行了同源性分析。结果从1828份流感样病例中检出甲型H1N1流感病毒阳性标本286份,阳性率15.6%。在开封地区首次获得甲型H

  1. DEVELOPMENT OF TEST KIT FOR DETECTION OF PANDEMIC STRAIN INFLUENZA VIRUS A (H1N1 2009 BY REAL TIME POLYMERASE CHAIN REACTION

    Directory of Open Access Journals (Sweden)

    S. V. Stepaniuk

    2013-04-01

    Full Text Available Influenza viruses A play an important role in the structure of the incidence of people with acute respiratory viral infection, which make up 90% from all other infectious diseases. According to the World Health Organization, only severe flu worldwide suffer annually 3.5 million, of which 45–60% are children. An economic loss from seasonal flu epidemic is in average about 85% of economic losses from infectious diseases in general. The experience of fighting the flu, accumulated over the years, has shown that to develop and deliver effective preventive measures necessary to build a system of permanent monitoring for influenza virus circulation, based on use of laboratory methods for accurate and rapid dentification and characterization of circulating strains of influenza virus A. Among the methods of laboratory diagnosis of influenza, the most effective is a method of polymerase chain reaction. Data on the evelopment of diagnostic test kits in the format of two-stage multiplex RTPCR-analysis for detection and genotyping of pandemic influenza virus A (H1N12009 are given. The results of laboratory and experimental research of «DIA Influenza H1N1» test system showed that it is effective and specific for detection of California pandemic influenza virus A (H1N12009 strains and can be used to diagnose disease caused by this strain of virus. Clinical trial of the course of the State registration by Ministry of Health of Ukraine have shown sensitivity and specificity of «DIA Influenza H1N1» test systems up to 100%.

  2. The response of the Liguria Region (Italy) to the pandemic influenza virus A/H1N1sv.

    Science.gov (United States)

    Amicizia, D; Cremonesi, I; Carloni, R; Schiaffino, S

    2011-09-01

    Influenza is a cause of acute respiratory disease. It has a typical epidemic nature during the winter season, but may also assume a pandemic pattern when a completely new virus spreads among humans. Influenza places a heavy economic and healthcare burden on both the National Health Service and society. During the 2009/2010 influenza pandemic season, the Liguria Region drew upon the specific skills of the various sectors of the Department of Health and Social Services. In collaboration with the Department of Health Sciences of the University of Genova, the Regional Health Agency (RHA) and other public organizations, steps were taken to address the issues of technical and scientific updating and the coordination of all the departments of Local Healthcare Units in Liguria. The main activities conducted at the regional level provided an adequate response to the influenza pandemic. These activities focused on Local and National Influenza Surveillance Systems, the regional Pandemic Plan, vaccination strategies for seasonal and pandemic influenza, and the communication of data from monitoring programs (sentinel physicians--syndromic surveillance). The prevention of influenza transmission and containment of epidemics and pandemics require effective communication strategies that should target the whole population.

  3. Novel triple reassortant H1N2 influenza viruses bearing six internal genes of the pandemic 2009/H1N1 influenza virus were detected in pigs in China.

    Science.gov (United States)

    Qiao, Chuanling; Liu, Liping; Yang, Huanliang; Chen, Yan; Xu, Huiyang; Chen, Hualan

    2014-12-01

    The pandemic A/H1N1 influenza viruses emerged in both Mexico and the United States in March 2009, and were transmitted efficiently in the human population. Transmissions of the pandemic 2009/H1N1 virus from humans to poultry and other species of mammals were reported from several continents during the course of the 2009 H1N1 pandemic. Reassortant H1N1, H1N2, and H3N2 viruses containing genes of the pandemic 2009/H1N1 viruses appeared in pigs in some countries. In winter of 2012, a total of 2600 nasal swabs were collected from healthy pigs in slaughterhouses located throughout 10 provinces in China. The isolated viruses were subjected to genetic and antigenic analysis. Two novel triple-reassortant H1N2 influenza viruses were isolated from swine in China in 2012, with the HA gene derived from Eurasian avian-like swine H1N1, the NA gene from North American swine H1N2, and the six internal genes from the pandemic 2009/H1N1 viruses. The two viruses had similar antigenic features and some significant changes in antigenic characteristics emerged when compared to the previously identified isolates. We inferred that the novel reassortant viruses in China may have arisen from the accumulation of the three types of influenza viruses, which further indicates that swine herds serve as "mixing vessels" for influenza viruses. Influenza virus reassortment is an ongoing process, and our findings highlight the urgent need for continued influenza surveillance among swine herds. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Pathogenesis of infection with 2009 pandemic H1N1 influenza virus in isogenic guinea pigs after intranasal or intratracheal inoculation.

    Science.gov (United States)

    Wiersma, Lidewij C M; Vogelzang-van Trierum, Stella E; van Amerongen, Geert; van Run, Peter; Nieuwkoop, Nella J; Ladwig, Mechtild; Banneke, Stefanie; Schaefer, Hubert; Kuiken, Thijs; Fouchier, Ron A M; Osterhaus, Albert D M E; Rimmelzwaan, Guus F

    2015-03-01

    To elucidate the pathogenesis and transmission of influenza virus, the ferret model is typically used. To investigate protective immune responses, the use of inbred mouse strains has proven invaluable. Here, we describe a study with isogenic guinea pigs, which would uniquely combine the advantages of the mouse and ferret models for influenza virus infection. Strain 2 isogenic guinea pigs were inoculated with H1N1pdm09 influenza virus A/Netherlands/602/09 by the intranasal or intratracheal route. Viral replication kinetics were assessed by determining virus titers in nasal swabs and respiratory tissues, which were also used to assess histopathologic changes and the number of infected cells. In all guinea pigs, virus titers peaked in nasal secretions at day 2 after inoculation. Intranasal inoculation resulted in higher virus excretion via the nose and higher virus titers in the nasal turbinates than intratracheal inoculation. After intranasal inoculation, infectious virus was recovered only from nasal epithelium; after intratracheal inoculation, it was recovered also from trachea, lung, and cerebrum. Histopathologic changes corresponded with virus antigen distribution, being largely limited to nasal epithelium for intranasally infected guinea pigs and more widespread in the respiratory tract for intratracheally infected guinea pigs. In summary, isogenic guinea pigs show promise as a model to investigate the role of humoral and cell-mediated immunities to influenza and their effect on virus transmission.

  5. 郴州市2009年流感病原学监测及A(H1N1)NA基因特征研究%AN ETIOLOGICAL MONITORING ON INFLUENZA AND THE GENETIC EVOLUTION OF NEURAMINIDASE GENE FOR SEASONAL H1N1 INFLUENZA A VIRUSES IN CHENZHOU IN 2009

    Institute of Scientific and Technical Information of China (English)

    谭徽; 付敏; 谢群; 罗文英; 刘爱平; 陈柏塘; 陈白鹭

    2012-01-01

    [Objective] To analyze the epidemic situation and distribution of types of influenza virus in Chenzhou in 2009, and study the genetic evolution of neuraminidase (NA) gene of influenza A/H1N1 virus. [Methods] Throat swab sam-ples were collected from patients with Influenza-like illness (ILI) in trie sentinel hospitals, then inoculated in Madin-Darby canine kidney (MDCK) cell lines. Trie types of influenza were identified by hemagglulination (HA) and hemagglutination inhi-bition (HI) teats. A/H1N1 influenza viruses were detected by reverse transcriptase-polymerase chain reaction (RT-PCR) in the influenza outbreaks. The NA genes of two strains of influenza viruses (A/HunanBerhu/1237/2009MApr and A/HunanBerhu/ 11291/2009_0ct) were sequenced to analyze their characteristic. [Results] A total of 2 226 throat swab specimens were col-lected, of which 109 strains were seasonal H1N1 influenza A viruses, 91 influenza A-H3N2 viruses, 30 novel influenza A/ H1N1 virus, 18 influenza B viruses. 3 040 samples were detected by PCR, of which 1 016 strains were positive for influenza virus (33.43%). Compare with the WHO recommended vaccine strain of 2009 (A/Brisbane/59/2007) , the nucleotide se-quence homology of the NA gene of A/HunanBerhu/1237/2009^Apr and A/HunanBerhu/11291/2009_Ocl are 99% and 98%. The genetic evolution analysis revealed that the NA gene of A/HunanBerhu/1237/2009_Apr had the closest genetic relationship with the vaccine strain, and some sites of the NA gene of A/HunanBerhu/11291/2009_Oct were mutated, [Conclusion] Sea-sonal H1N1 influenza A viruses was the dominant strain during January to June. July to September was seasonal H3N2. October to November was Novel influenza A/H1N1 virus, which caused the emergence of pandemic influenza H1N1. The variation of NA gene of seasonal A/H1N1 has occurred in a certain degree. So it is very necessary to continuously monitor the variant of influen-za A virus%[目的]了解2009年郴州市流感病毒流行株的病原学特

  6. INFECCIÓN POR VIRUS PANDÉMICO (H1N1 2009 EN ANDALUCÍA

    Directory of Open Access Journals (Sweden)

    José María Mayoral Cortés

    2010-01-01

    Full Text Available Desde que en abril de 2009 la Organización Mundial de la Salud (OMS alertó de la existencia de casos de infección humana por un nuevo virus de la gripe AH1N1 de origen porcino, las autoridades sanitarias de Andalucía activaron un plan específico de actuación para dar respuesta a la crisis sanitaria. Las actividades de vigilancia desarrolladas permitieron disponer de información oportuna sobre las características clínicas, epidemiológicas y virológicas de la enfermedad. En los primeros días se pusieron en marcha planes de contingencia basados en la vigilancia epidemiológica y medidas de control de brotes mediante sistemas de alerta y respuesta rápida. Tras la declaración de fase 6 de alerta pandémica la vigilancia centinela de gripe y de casos graves fueron de utilidad para la planificación de servicios sanitarios, para reducir la transmisión e identificar y para proteger a los grupos de población más vulnerables. El comportamiento de la gripe pandémica en Andalucía ha sido similar al observado en el resto del mundo. La tasa de ataque fue parecida a la de una temporada de gripe estacional y el pico de máxima incidencia se alcanzó en la semana 46/2009. La mayoría de los casos fueron leves y afectó sobre todo a población joven. En los casos hospitalizados la media de edad fue de 32 años. Las patologías previas de base y factores de riesgo mas frecuentes presentes en los casos graves fueron enfermedades pulmonares, tabaquismo y obesidad mórbida (IMC>40. Un escenario de impacto de la onda pandémica en Andalucía, con una tasa de ataque esperada de entre el 2 y 5%, se preparó teniendo en cuenta lo observado durante la onda epidémica en los países del hemisferio sur. Las características de la epidemia en cuanto a su magnitud, gravedad y letalidad, se ajustaron a este escenario utilizado.

  7. In silico characterization of the functional and structural modules of the hemagglutinin protein from the swine-origin influenza virus A (H1N1)-2009

    Institute of Scientific and Technical Information of China (English)

    Christopher; VAVRICKA; GAO; George; F

    2010-01-01

    The 2009 swine-origin influenza virus (S-OIV,H1N1 subtype) has developed into a new pandemic influenza as announced by the World Health Organization.In order to uncover clues about the determinants for virulence and pathogenicity of the virus,we characterized the functional modules of the surface glycoprotein hemagglutinin (HA),the most important protein in molecular epidemiology and pathogenesis of influenza viruses.We analyzed receptor binding sites,basic patch,neutralization antibody epitopes and T cell epitopes in the HA protein of the current S-OIV according to the corresponding functional and structural modules previously characterized in other H1 HA molecules or HA molecules of other subtypes.We compared their differences and similarities systematically.Based on the amino acids defined as the functional and structural modules,the HA protein of 2009 S-OIV should specifically bind to the human 2,6-receptor.The D225G/E mutation in HA,which is found in some isolates,may confer dual binding specificity to the 2,3and 2,6-receptor based on previously reported work.This HA variant contains two basic patches,one of which results in increased basicity,suggesting enhanced membrane fusion function.The 2009 S-OIV HA also has an extra glycosylation site at position 276.Four of the five antibody neutralization epitopes identified in A/RP/8/34(H1N1) were exposed,but the other was hidden by a glycosylation site.The previously identified cytotoxic T cell epitopes in various HA molecules were summarized and their corresponding sequences in 2009 S-OIV HA were defined.These results are critical for understanding the pathogenicity of the virus and host immune response against the virus.

  8. Analysis of HA gene sequence of a subtype H1N1 swine influenza virus isolated from Guangxi strains%H1N1猪流感病毒广西分离株HA基因序列分析

    Institute of Scientific and Technical Information of China (English)

    颜健华; 梁丹洁; 李春英; 徐贤坤; 胡巧云; 孙翔翔; 何奇松; 熊毅

    2013-01-01

    [目的]了解H1N1猪流感病毒广西分离株的分子特征,为广西猪流感疫情监控提供参考依据.[方法]采用RT-PCR对2011年分离获得的H1N1猪流感病毒广西分离株(A/swine/Guangxi/1/2011)的HA基因进行扩增,然后利用DNASTAR分析软件对测序基因片段进行整个阅读框架的核苷酸序列及其推导氨基酸序列同源性比对分析,并用MEGA 4.0绘制遗传进化树.[结果]广西分离株HA基因长1701 bp,编码566个氨基酸,核苷酸序列与经典SIV的同源性为88.0%~99.6%,与季节性H1N1人流感病毒的同源性为76.3%~77.3%,与欧洲类禽SⅣ分离株的同源性为72.9%~75.4%,与2009甲型H1N1流感病毒的同源性为99.2%~99.6%;从核苷酸遗传进化树可知,广西分离株与类禽H1N1流感病毒和人H1N1流感病毒分离株的亲缘关系较远,而与2009甲型H 1N l流感病毒分离株的亲缘关系最近.广西分离毒株HA基因的裂解位点序列为IPSIQSR↓G,具有典型低致病性流感病毒的分子生物学特征;共有8个糖基化位点,其中6个位于HAl区,两个位于HA2区;广西分离株HA蛋白RBS位点的氨基酸同时具有人和猪流感病毒的特点.[结论]广西分离株(A/swine/Guangxi/1/2011)属于2009甲型H1N1流感病毒.%[Objective]This study was to determine molecular biology information of HA gene of H 1N 1 swine influenza virus isolated from Guangxi strains to provide references for monitoring swine flu in Guangxi.[Method]To analyze HA gene of H1N1 from Genbank,the primer was designed,and then HA genes of A/swine/Guangxi/1/2011 (H1N1) influenza virus were cloned,sequenced and compared via DNASTAR software.A phylogenetic tree was made using MEGA 4.0.[Result]The results indicated that the length of HA gene was 1701 bp and coded for 566 amino acids.Comparing with classical swine influenza H1N1,human-like H1N1 and Eurasian avian-like H1N1,the nucleotide homologies of HA genes were from 88.0% to 99.6%,from 76.3% to

  9. Pregnancy-Related Immune Adaptation Promotes the Emergence of Highly Virulent H1N1 Influenza Virus Strains in Allogenically Pregnant Mice.

    Science.gov (United States)

    Engels, Géraldine; Hierweger, Alexandra Maximiliane; Hoffmann, Julia; Thieme, René; Thiele, Swantje; Bertram, Stephanie; Dreier, Carola; Resa-Infante, Patricia; Jacobsen, Henning; Thiele, Kristin; Alawi, Malik; Indenbirken, Daniela; Grundhoff, Adam; Siebels, Svenja; Fischer, Nicole; Stojanovska, Violeta; Muzzio, Damián; Jensen, Federico; Karimi, Khalil; Mittrücker, Hans-Willi; Arck, Petra Clara; Gabriel, Gülsah

    2017-03-08

    Pregnant women are at high risk for severe influenza disease outcomes, yet insights into the underlying mechanisms are limited. Here, we present models of H1N1 infection in syngenic and allogenic pregnant mice; infection in the latter mirrors the severe course of 2009 pandemic influenza in pregnant women. We found that the anti-viral immune response in the pregnant host was significantly restricted as compared to the non-pregnant host. This included a reduced type I interferon response as well as impaired migration of CD8(+) T cells into the lung. The multi-faceted failure to mount an anti-viral response in allogenic pregnant mice resulted in a less stringent selective environment that promoted the emergence of 2009 H1N1 virus variants that specifically counteract type I interferon response and mediate increased viral pathogenicity. These insights underscore the importance of influenza vaccination compliance in pregnant women and may open novel therapeutic avenues. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Acute sleep deprivation has no lasting effects on the human antibody titer response following a novel influenza A H1N1 virus vaccination

    Directory of Open Access Journals (Sweden)

    Benedict Christian

    2012-01-01

    Full Text Available Abstract Background Experimental studies in humans have yielded evidence that adaptive immune function, including the production of antigen-specific antibodies, is distinctly impaired when s