کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5675064 1594216 2017 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
PB2 substitutions V598T/I increase the virulence of H7N9 influenza A virus in mammals
موضوعات مرتبط
علوم زیستی و بیوفناوری ایمنی شناسی و میکروب شناسی ویروس شناسی
پیش نمایش صفحه اول مقاله
PB2 substitutions V598T/I increase the virulence of H7N9 influenza A virus in mammals
چکیده انگلیسی


- Substitutions at positions PB2-389 and -598 were identified with potential effect on virus pathogenicity.
- PB2-K389R and -V598T/I substitutions enhanced virus growth capacity in human and mammalian cells.
- The PB2-K389R and -V598T/I increased virus transcription/replication by producing more viral RNAs in human cells.
- The PB2-K389R and -V598T/I substitutions elevated the polymerase activity in human cells.
- The PB2-V598T/I substitutions increased virus replication and virulence in mice.

PB2 is one of the subunits of the influenza A virus (IAV) polymerase complex. By bioinformatics analysis we identified PB2 substitutions at positions 389 and 598 among IAV isolates from humans, which might associate with viral pathogenicity. To evaluate the biological significance of these substitutions, PB2-K389R and -V598T/I mutant viruses of avian H7N9 IAVs were generated by reverse genetics. Compared to the wild type, the mutant viruses displayed an enhanced growth capacity in human and mammalian cells. Meanwhile, they presented increased transcription and replication by producing higher levels of viral mRNA, cRNA and vRNA. Minireplicon assays indicated that the polymerase activity was elevated by these substitutions. Notably, the PB2-V598T/I substitutions substantially increased virus replication and virulence in mice. Together, we demonstrated that the substitutions PB2-V598T/I contributed to higher IAV replication and virulence in mammals, which added to the knowledge of IAV virulence determinants and benefited the surveillance of IAVs.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Virology - Volume 501, 15 January 2017, Pages 92-101
نویسندگان
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