H7N9 Influenza A Virus Exhibits Importin-α7-Mediated Replication in the Mammalian Respiratory Tract.

The acute respiratory distress syndrome (ARDS) is the leading cause of death in influenza A virus (IAV)-infected patients. Hereby, the cellular importin-α7 gene plays a major role. It promotes viral replication in the lung, thereby increasing the risk for the development of pneumonia complicated by ARDS.

PB2 subunit of avian influenza virus subtype H9N2: a pandemic risk factor.

Avian influenza viruses of subtype H9N2 that are found worldwide are occasionally transmitted to humans and pigs. Furthermore, by co-circulating with other influenza subtypes, they can generate new viruses with the potential to also cause zoonotic infections, as observed in 1997 with H5N1 or more recently with H7N9 and H10N8 viruses. Comparative analysis of the adaptive mutations in polymerases of different viruses indicates that their impact on the phylogenetically related H9N2 and H7N9 polymerases is higher than on the non-related H7N7 and H1N1pdm09 polymerases.

Adaptive mutation PB2 D701N promotes nuclear import of influenza vRNPs in mammalian cells.

The segmented genome of influenza viruses is translocated into the nucleus to initiate transcription and replication. The gene segments are present as viral ribonucleoprotein (vRNP) particles composed of RNA, multiple copies of the nucleoprotein (NP), and the polymerase subunits PB1, PB2 and PA. The PB2 subunit and each NP monomer contain a nuclear localisation signal (NLS) that binds to importin-α.

TMPRSS2 is a host factor that is essential for pneumotropism and pathogenicity of H7N9 influenza A virus in mice.

Unlabelled: Cleavage of the hemagglutinin (HA) by host proteases is essential for the infectivity of influenza viruses. Here, we analyzed the role of the serine protease TMPRSS2, which activates HA in the human respiratory tract, in pathogenesis in a mouse model. Replication of the human H7N9 isolate A/Anhui/1/13 and of human H1N1 and H3N2 viruses was compared in TMPRSS2 knockout (TMPRSS2(-/-)) and wild-type (WT) mice.

Matriptase, HAT, and TMPRSS2 activate the hemagglutinin of H9N2 influenza A viruses.

Influenza A viruses of the subtype H9N2 circulate worldwide and have become highly prevalent in poultry in many countries. Moreover, they are occasionally transmitted to humans, raising concern about their pandemic potential. Influenza virus infectivity requires cleavage of the surface glycoprotein hemagglutinin (HA) at a distinct cleavage site by host cell proteases.

Oseltamivir-resistant variants of the 2009 pandemic H1N1 influenza A virus are not attenuated in the guinea pig and ferret transmission models.

Oseltamivir is routinely used worldwide for the treatment of severe influenza A virus infection, and should drug-resistant pandemic 2009 H1N1 viruses become widespread, this potent defense strategy might fail. Oseltamivir-resistant variants of the pandemic 2009 H1N1 influenza A virus have been detected in a substantial number of patients, but to date, the mutant viruses have not moved into circulation in the general population. It is not known whether the resistance mutations in viral neuraminidase (NA) reduce viral fitness.