PA Mutations Inherited during Viral Evolution Act Cooperatively To Increase Replication of Contemporary H5N1 Influenza Virus with an Expanded Host Range
Copyright policy )PA Mutations Inherited during Viral Evolution Act Cooperatively To Increase Replication of Contemporary H5N1 Influenza Virus with an Expanded Host Range
Clade 2.2.1 avian influenza viruses (H5N1) are unique to Egypt and have caused the highest number of human H5N1 influenza cases worldwide, presenting a serious global public health threat. These viruses may have the greatest evolutionary potential for adaptation from avian hosts to human hosts. Using a comprehensive phylogenetic approach, we identified several novel clade 2.2.1 virus polymerase mutations that increased viral replication in vitro in human cells and in vivo in mice. These mutations were in the polymerase PA subunit and acted cooperatively with the E627K mutation in the PB2 polymerase subunit to provide higher replication in contemporary clade 2.2.1.2 viruses than in ancestral clade 2.2.1 viruses. These data indicated that ongoing clade 2.2.1 dissemination in the field has driven PA mutations to modify viral replication to enable host range expansion, with a higher public health risk for humans.
- Damanhour University Egypt
- Osaka University Japan
- Kindai University Japan
- Kyoto Prefectural University of Medicine Japan
Models, Molecular, Influenza A Virus, H5N1 Subtype, Viral Nonstructural Proteins, RNA-Dependent RNA Polymerase, Virus Replication, Adaptation, Physiological, Host Specificity, Cell Line, Evolution, Molecular, Mice, Orthomyxoviridae Infections, Mutation, Pathogenesis and Immunity, Animals, Humans, Egypt, Chickens, Phylogeny
Models, Molecular, Influenza A Virus, H5N1 Subtype, Viral Nonstructural Proteins, RNA-Dependent RNA Polymerase, Virus Replication, Adaptation, Physiological, Host Specificity, Cell Line, Evolution, Molecular, Mice, Orthomyxoviridae Infections, Mutation, Pathogenesis and Immunity, Animals, Humans, Egypt, Chickens, Phylogeny
selected citations These citations are derived from selected sources.This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).14 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Average impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
Citations provided by BIP!Popularity provided by BIP!