Genetic characterization of HA gene of low pathogenic H9N2 influenza viruses isolated in Israel during 2006–2012 periods

Davidson, Irit; Shkoda, I.; Golender, Natalia; Perk, Shimon; Lapin, K.; Khinich, Yevgeny; Panshin, Alexander

doi:10.1007/s11262-012-0852-4

Cited by 25 publications

(23 citation statements)

References 38 publications

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“…In our study except for position 226, no additional changes were observed in the HA RBS that could enable avian-human transmission. Similar type of observations were also reported for HA gene of H9N2 viruses prevalent in Israel after detailed molecular analysis and it was found that H9N2 viruses circulating in the Israel are predominantly of G1 lineage and harbors Q226L substitution in HA gene (Davidson et al 20132014). The Q226L substitution seen in RBS of H9N2 avian isolates is important as it confers human virus like receptor specificity and binds more strongly with 2-6-linked sialic acid receptors as seen in human H3N2 viruses (Matrosovich et al 2001) in contrast to viruses lacking this substitution which binds more strongly with 2-3 linked sialic acid receptors.…”

Section: Discussionsupporting

confidence: 74%

Isolation and characterization of H9N2 influenza virus isolates from poultry respiratory disease outbreak

et al. 2014

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The present study reports isolation and characterization of H9N2 virus responsible for disease characterized by symptoms including difficulty in respiration, head swelling, nasal discharge, reduced feed intake, cyanotic comb, reduced egg production and mortality. Virus isolation from allantoic fluid inoculated with tracheal aspirates and whole genome sequencing of two isolates were performed on an Ion-Torrent sequencer. Phylogenetic analysis revealed that the two H9N2 isolates are reassortant viruses showing a G1-like lineage for HA, NA and NP, a Hok/49/98-like lineage for PB1 and PA, PK/UDL-01/05-like lineage for PB2, IL/90658/00-like lineage for NS and an unknown lineage for M gene. Analyses of the HA cleavage site showed a sequence of (333PARSSR↓GL340) indicating that these isolates are of low pathogenicity. Isolate 2 has leucine at amino acid position 226, a substitution which is associated with mammalian adaptation of avian influenza virus. Isolate 1 has the S31N substitution in the M2 gene that has been associated with drug resistance as well as R57Q and C241Y mutations in the NP gene which are associated with human adaptation. The result reported here gives deep insight in to H9N2 viruses circulating in domestic poultry of India and supports the policy of active efforts to control and manage H9N2 infections in Indian poultry.Electronic supplementary materialThe online version of this article (doi:10.1186/2193-1801-3-196) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 74%

Isolation and characterization of H9N2 influenza virus isolates from poultry respiratory disease outbreak

et al. 2014

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“…Mutations in the HA glycoprotein are known to be particularly influential on modulating the overlapping and interrelated properties of receptor specificity, host and tissue tropism, pathogenicity, and antigenicity (32, 43, 50). Conventional avian influenza vaccines typically lose efficacy as HAs undergo antigenic drift, and several research groups have suggested that the widespread use of poultry vaccines may even contribute to driving antigenic drift (21, 22, 24, 51, 52). Recently, we generated a panel of “antigenic drift-like” escape mutants (through in vitro selection with MAbs), some of which contained deletions within the 220 loop region of the HA RBS (34).…”

Section: Discussionmentioning

confidence: 99%

“…The possibility that vaccine-induced immunity may influence antigenic drift was previously explored through studies with comparative molecular epidemiology; however, the underlying process remains poorly understood and merits further investigation (22, 51, 56). Both deletion mutant viruses tested here for their growth in primary human airway cells, Δ208–213 and Δ210–213, exhibited increased replication compared to the wt UDL1/08 virus.…”

Section: Discussionmentioning

confidence: 99%

Immune Escape Variants of H9N2 Influenza Viruses Containing Deletions at the Hemagglutinin Receptor Binding Site Retain Fitness In Vivo and Display Enhanced Zoonotic Characteristics

Peacock

Benton

James

et al. 2017

J Virol

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H9N2 avian influenza viruses are enzootic in poultry across Asia and North Africa, where they pose a threat to human health as both zoonotic agents and potential pandemic candidates. Poultry vaccination against H9N2 viruses has been employed in many regions; however, vaccine effectiveness is frequently compromised due to antigenic drift arising from amino acid substitutions in the major influenza virus antigen hemagglutinin (HA). Using selection with HA-specific monoclonal antibodies, we previously identified H9N2 antibody escape mutants that contained deletions of amino acids in the 220 loop of the HA receptor binding sites (RBSs). Here we analyzed the impact of these deletions on virus zoonotic infection characteristics and fitness. We demonstrated that mutant viruses with RBS deletions are able to escape polyclonal antiserum binding and are able to infect and be transmitted between chickens. We showed that the deletion mutants have increased binding to human-like receptors and greater replication in primary human airway cells; however, the mutant HAs also displayed reduced pH and thermal stability. In summary, we infer that variant influenza viruses with deletions in the 220 loop could arise in the field due to immune selection pressure; however, due to reduced HA stability, we conclude that these viruses are unlikely to be transmitted from human to human by the airborne route, a prerequisite for pandemic emergence. Our findings underscore the complex interplay between antigenic drift and viral fitness for avian influenza viruses as well as the challenges of predicting which viral variants may pose the greatest threats for zoonotic and pandemic emergence.IMPORTANCE Avian influenza viruses, such as H9N2, cause disease in poultry as well as occasionally infecting humans and are therefore considered viruses with pandemic potential. Many countries have introduced vaccination of poultry to try to control the disease burden; however, influenza viruses are able to rapidly evolve to escape immune pressure in a process known as “antigenic drift.” Previously, we experimentally generated antigenic-drift variants in the laboratory, and here, we test our “drifted” viruses to assess their zoonotic infection characteristics and transmissibility in chickens. We found that the drifted viruses were able to infect and be transmitted between chickens and showed increased binding to human-like receptors. However, the drift mutant viruses displayed reduced stability, and we predict that they are unlikely to be transmitted from human to human and cause an influenza pandemic. These results demonstrate the complex relationship between antigenic drift and the potential of avian influenza viruses to infect humans.

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“…However, it is evident that there is a lack of systematic mutagenic studies of this important position. In addition, there is a small and yet significant number of influenza PB2 segments that have a valine (V) at this position (Davidson et al, 2013; Golender et al., 2008). It is not known whether vRNPs with an atypical amino acid residue at this position behave differently from those carrying a K or E at the same position.…”

Section: Introductionmentioning

confidence: 99%

Influenza A viruses with different amino acid residues at PB2-627 display distinct replication properties in vitro and in vivo : Revealing the sequence plasticity of PB2-627 position

Chin

Mok

et al. 2014

Virology

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Sequence analyses of influenza PB2 sequences indicate that the 627 position almost exclusively contains either lysine (K) or glutamic acid (E), suggesting a high sequence constraint at this genetic marker. Here, we used a site-directed random mutagenesis method to demonstrate that PB2-627 position has a high sequence plasticity. Recombinant viruses carrying various amino acid residues at this position are viable in cell cultures. These PB2-627 mutants showed various polymerase activities and replication kinetics in mammalian and avian cells as well as pathogenicity in mice. Serially passaging these mutants in MDCK cells generated some compensatory PB2 mutations that can restore polymerase activities of the PB2-627 mutants. Of these, PB2-D309N was identified as a novel one. Besides showing that influenza virus can tolerate a wide range of amino acid residues at the PB2-627 position, this study also demonstrates a potential strategy to identify novel mutations that can enhance viral polymerase.

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Genetic characterization of HA gene of low pathogenic H9N2 influenza viruses isolated in Israel during 2006–2012 periods

Cited by 25 publications

References 38 publications

Isolation and characterization of H9N2 influenza virus isolates from poultry respiratory disease outbreak

Isolation and characterization of H9N2 influenza virus isolates from poultry respiratory disease outbreak

Immune Escape Variants of H9N2 Influenza Viruses Containing Deletions at the Hemagglutinin Receptor Binding Site Retain Fitness In Vivo and Display Enhanced Zoonotic Characteristics

Influenza A viruses with different amino acid residues at PB2-627 display distinct replication properties in vitro and in vivo : Revealing the sequence plasticity of PB2-627 position

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