RT Journal Article SR Electronic(1) A1 Ran, Zhiguang A1 Chen, Ying A1 Shen, Huigang A1 Xiang, Xiaoxiao A1 Liu, Qinfang A1 Bawa, Bhupinder A1 Qi, Wenbao A1 Zhu, Laihua A1 Young, Alan A1 Richt, Juergen A1 Ma, Wenjun A1 Li, FengYR 2013 T1 In vitro and in vivo replication of influenza A H1N1 WSN33 viruses with different M1 proteins JF Journal of General Virology, VO 94 IS 4 SP 884 OP 895 DO https://doi.org/10.1099/vir.0.046219-0 PB Microbiology Society, SN 1465-2099, AB The M1 protein is a major structural protein that has multiple functions in various steps within the life cycle of the influenza A virus (IAV). However, little is currently known about the role of M1 in IAV replication in vivo and the associated pathogenesis. In this study, six isogenic H1N1 WSN33 viruses, constructed to express unique M1 proteins derived from various strains, subtypes or WSN33 itself, were tested to determine in vitro and in vivo functional exchangeability of M1 proteins in the replication and pathogenesis of the WSN33 virus. Despite five chimeric M1 viruses replicating to levels similar to those of the parental WSN33 virus in cell cultures, all M1 chimeras exhibited improved replication and enhanced virulence in mice when compared with the WSN33 virus. Interestingly, M1 proteins derived from swine viruses caused more severe clinical diseases than those from human or quail. These data indicate that the M1 protein is an important determinant of viral replication and pathogenic properties in mice, although the functions of M1 observed in vivo are not adequately reflected in simple infections of cultured cells. Chimeric M1 viruses that are variable in their clinical manifestations described here will aid future understanding of the role of M1 in IAV pathogenesis., UL https://www.microbiologyresearch.org/content/journal/jgv/10.1099/vir.0.046219-0