PMID- 23616660 OWN - NLM STAT- MEDLINE DCOM- 20130812 LR - 20211021 IS - 1098-5514 (Electronic) IS - 0022-538X (Print) IS - 0022-538X (Linking) VI - 87 IP - 13 DP - 2013 Jul TI - Adaptation of avian influenza A virus polymerase in mammals to overcome the host species barrier. PG - 7200-9 LID - 10.1128/JVI.00980-13 [doi] AB - Avian influenza A viruses, such as the highly pathogenic avian H5N1 viruses, sporadically enter the human population but often do not transmit between individuals. In rare cases, however, they establish a new lineage in humans. In addition to well-characterized barriers to cell entry, one major hurdle which avian viruses must overcome is their poor polymerase activity in human cells. There is compelling evidence that these viruses overcome this obstacle by acquiring adaptive mutations in the polymerase subunits PB1, PB2, and PA and the nucleoprotein (NP) as well as in the novel polymerase cofactor nuclear export protein (NEP). Recent findings suggest that synthesis of the viral genome may represent the major defect of avian polymerases in human cells. While the precise mechanisms remain to be unveiled, it appears that a broad spectrum of polymerase adaptive mutations can act collectively to overcome this defect. Thus, identification and monitoring of emerging adaptive mutations that further increase polymerase activity in human cells are critical to estimate the pandemic potential of avian viruses. FAU - Manz, Benjamin AU - Manz B AD - Department of Virology, Institute for Medical Microbiology and Hygiene, University of Freiburg, Freiburg, Germany. FAU - Schwemmle, Martin AU - Schwemmle M FAU - Brunotte, Linda AU - Brunotte L LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20130424 PL - United States TA - J Virol JT - Journal of virology JID - 0113724 RN - 0 (Nucleoproteins) RN - 0 (Viral Proteins) RN - EC 2.7.7.6 (DNA-Directed RNA Polymerases) SB - IM MH - Adaptation, Biological/*genetics MH - Animals MH - Birds MH - DNA-Directed RNA Polymerases/genetics/*metabolism MH - Host-Pathogen Interactions/*genetics MH - Humans MH - Influenza A virus/*enzymology MH - Influenza in Birds/*virology MH - Models, Biological MH - Mutation/genetics MH - Nucleoproteins/*genetics MH - Species Specificity MH - Viral Proteins/genetics/*metabolism MH - Virus Replication/genetics/physiology PMC - PMC3700283 EDAT- 2013/04/26 06:00 MHDA- 2013/08/13 06:00 PMCR- 2014/01/01 CRDT- 2013/04/26 06:00 PHST- 2013/04/26 06:00 [entrez] PHST- 2013/04/26 06:00 [pubmed] PHST- 2013/08/13 06:00 [medline] PHST- 2014/01/01 00:00 [pmc-release] AID - JVI.00980-13 [pii] AID - 00980-13 [pii] AID - 10.1128/JVI.00980-13 [doi] PST - ppublish SO - J Virol. 2013 Jul;87(13):7200-9. doi: 10.1128/JVI.00980-13. Epub 2013 Apr 24.