A Single N66S Mutation in the PB1-F2 Protein of Influenza A Virus Increases Virulence by Inhibiting the Early Interferon Response
            <i>In Vivo</i>

Conenello, Gina; Tisoncik, Jennifer R.; Rosenzweig, Elizabeth; Varga, Zsuzsanna T.; Palese, Peter; Katze, Michael G.

doi:10.1128/jvi.01987-10

Cited by 141 publications

(166 citation statements)

References 35 publications

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“…In all of the H5N2 isolates in this study, the PDZ binding sequence at the C-terminus of the NS1 protein was ESEV and the residue at position 138 was Phe (F), suggesting increased virulence in mammals [33,53]. In addition to the mutation in the NS1 gene, the mutation N66S, associated with increased virulence of influenza A viruses in mice [54], was found in the PB1-F2 gene of two isolates (9UO036 and 9UO139). Interestingly, the Ibaraki strain (a reference strain that caused an outbreak in Japan during 2005) did not contain either S66 or N66 in the PB1-F2 gene.…”

Section: Discussionmentioning

confidence: 99%

Genetic characterization of H5N2 influenza viruses isolated from wild birds in Japan suggests multiple reassortment

et al. 2016

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Low-pathogenic avian influenza viruses (LPAIVs) of the H5 subtype can mutate to highly pathogenic forms, potentially destabilizing the poultry industry. Wild migratory birds are considered a natural reservoir of LPAIVs capable of dispersing both high-and low-pathogenic forms of the virus. Therefore, surveillance and characterization of AIV in wild birds are essential. Here, we report on the isolation and genetic characterization of 10 AIVs of the H5N2 subtype obtained through surveillance in Hokkaido, Japan, during 2009 and 2011. Fullgenome sequencing revealed that the H5 and N2 genes of these isolates are all closely related to each other, belonging to the Eurasian avian-like lineage, but they are unrelated to H5 highly pathogenic strains of clade 2.3.4.4. The internal genes of the isolates were found to be diverse, consistent with our hypothesis that these H5N2 strains have undergone multiple reassortment events. Even though all of the H5N2 isolates were characterized as LPAIV based on the amino acid sequences at the HA cleavage site, this analysis demonstrates a diverse pool of precursors that may seed future outbreaks in poultry and possible human transmissions, suggesting the need for high-quality surveillance.

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Section: Discussionmentioning

confidence: 99%

Genetic characterization of H5N2 influenza viruses isolated from wild birds in Japan suggests multiple reassortment

et al. 2016

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“…In this study, we examined 42 natural isolates of the influenza A virus of the H1N1, H3N1, H3N2, H3N6, H3N8, H4N6, H5N3, H6N2, H7N9, H9N2, and H11N9 subtypes for the presence of the known to date pathogenicity factors that are described in the literature [9,10,12]. Our results showed that markers like the ESEV sequence of the PDZ domain ligand in the NS1 viral protein and changes in the reading frame of the viral protein PB1-F2 (N66S replacement) in the context of the wild duck influenza virus genome are not associated with the virus pathogenicity for mice.…”

Section: Discussionmentioning

confidence: 99%

“…Those changes include the following: appearance of a polybasic sequence in the HA cleavage site of HPAIV [3]; deletion in the stem section of NA [4]; the E627K mutation in the polymerase protein PB2 that increases the rate of virus replication [5][6][7]; substitution of N66S in PB1-F2 protein that accelerates the nuclear transport [8][9][10]; and the substitutions in the nonstructural protein NS1 of HPAIV that lead to the efficient suppression of the host interferon synthesis [7,[11][12][13].…”

Section: Introductionmentioning

confidence: 99%

The use of microarrays for the identification of the origin of genes of avian influenza viruses in wild birds

Heydarov

Nf²,

Boravleva³

et al. 2017

Microbiology Independent Research Journal (MIR Journal)

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Forty-two strains of avian influenza viruses were isolated from the wild waterfowls' feces in the city of Moscow. These viruses, as well as reference strains and some experimental reassortants, were analyzed by microarrays. The microarrays contained 176 probes to the different segments of influenza virus genome. The microarray helps to determine 1) the hemagglutinin and neuraminidase proteins subtype; 2) the primary structure of the C-terminal sequence of the viral NS1 protein, which serves as a ligand for the PDZ domain; 3) the presence of stop codons in the reading frame of PB1-F2 as well as the N66S substitution in the PB1-F2 viral protein; 4) the presence of the polybasic site for hemagglutinin cleavage. The viruses of the H3N1, H3N6, H3N8, H4N6, H1N1, H5N3, and H11N9 subtypes were identified from the group of wild birds' isolates. All isolates contained the ESEV sequence at the C-terminus of the NS1 protein and the full-length reading frame for the PB1-F2 protein. The replacement of N66S in PB1-F2 was found in six strains. However, the presence of the ESEV sequence (ligand of PDZ domain) in the NS1 virus protein and the N66S substitution in PB1-F2 did not lead to the pathogenicity of these viruses for mice. All isolates demonstrated high yield growth in chicken embryos and were infectious and immunogenic for mice, but did not induce any clinical symptoms.

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“…Мутация E627K в белке PB2 способствует повышению активности ви-русной полимеразы и улучшению репродукции ви-руса [5][6][7]. Замена N66S в рамке считывания PB1-F2 ускоряет ядерный транспорт [8][9][10]. В неструктурном белке NS1 появляются замены, приводящие к эффек-тивному подавлению синтеза интерферона в хозяй-ской клетке [7,[11][12][13].…”

Section: Mir-journalorgunclassified

“…В работе проанализировано 42 природных изолята вируса гриппа А субтипов H1N1, H3N1, H3N2, H3N6, H3N8, H4N6, H5N3, H6N2, H7N9, H9N2 и H11N9 на на-личие известных на сегодняшний день и описанных в литературе факторов патогенности [9,10,12]. В ре-зультате выявлено, что такие маркеры, как последо-вательность ESEV лиганда PDZ-домена в вирусном белке NS1 и замена N66S в рамке считывания вирус-ного белка PB1-F2, в контексте генома вирусов грип-па диких уток не связана с патогенностью вируса для мышей.…”

Section: обсуж дениеunclassified

Применение Микрочипов Для Идентификации Происхождения Генов Вирусов Гриппа Диких Птиц

Гейдаров¹,

Nf²,

Боравлева³

et al. 2017

Microbiology Independent Research Journal (MIR Journal)

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В черте города Москвы из фекалий диких водоплавающих птиц изолировали 42 штамма вируса гриппа птиц и проанализировали их на микрочипах «Биогрипп», которые содержат 176 зондов к различным участкам генома вирусов гриппа. Микрочип позволяет определять: 1) субтип поверхностных белков гемагглютинина и нейраминидазы; 2) структуру С-концевой последовательности вирусного белка NS1, влияющую на степень ингибирования транскрипции клеточных хозяйских генов, в том числе ответственных за синтез интерферона; 3) наличие стоп-кодонов и мутацию N66S в рамке считывания вирусного белка PB1-F2, 4) наличие полиосновного сайта протеолитического расщепления гемагглютинина. Среди изолятов от диких птиц идентифицированы вирусы гриппа субтипов H3N1, H3N6, H3N8, H4N6, H1N1, H5N3 и H11N9. Все они содержали последовательность ESEV на С-конце белка NS1, полноразмерную рамку считывания для белка PB1-F2. Замена N66S в PB1-F2 обнаружена у шести штаммов. Однако такие маркеры патогенности, как последовательность ESEV (лиганд PDZ-домена) в вирусном белке NS1 и замена N66S PB1-F2 в контексте генома вирусов гриппа диких уток, не делали вирус патогенным для мышей. Все изоляты были высокоурожайны в куриных эмбрионах, инфекционны и иммуногенны для мышей, но не вызывали у этих животных клинических симптомов заболевания.

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A Single N66S Mutation in the PB1-F2 Protein of Influenza A Virus Increases Virulence by Inhibiting the Early Interferon Response In Vivo

Cited by 141 publications

References 35 publications

Genetic characterization of H5N2 influenza viruses isolated from wild birds in Japan suggests multiple reassortment

Genetic characterization of H5N2 influenza viruses isolated from wild birds in Japan suggests multiple reassortment

The use of microarrays for the identification of the origin of genes of avian influenza viruses in wild birds

Применение Микрочипов Для Идентификации Происхождения Генов Вирусов Гриппа Диких Птиц

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