Emergence of Highly Pathogenic Avian Influenza A(H5N1) Virus PB1-F2 Variants and Their Virulence in BALB/c Mice

Journal of Virology
Ram P KamalIan A York

Abstract

Influenza A viruses (IAVs) express the PB1-F2 protein from an alternate reading frame within the PB1 gene segment. The roles of PB1-F2 are not well understood but appear to involve modulation of host cell responses. As shown in previous studies, we find that PB1-F2 proteins of mammalian IAVs frequently have premature stop codons that are expected to cause truncations of the protein, whereas avian IAVs usually express a full-length 90-amino-acid PB1-F2. However, in contrast to other avian IAVs, recent isolates of highly pathogenic H5N1 influenza viruses had a high proportion of PB1-F2 truncations (15% since 2010; 61% of isolates in 2013) due to several independent mutations that have persisted and expanded in circulating viruses. One natural H5N1 IAV containing a mutated PB1-F2 start codon (i.e., lacking ATG) was 1,000-fold more virulent for BALB/c mice than a closely related H5N1 containing intact PB1-F2. In vitro, we detected expression of an in-frame protein (C-terminal PB1-F2) from downstream ATGs in PB1-F2 plasmids lacking the well-conserved ATG start codon. Transient expression of full-length PB1-F2, truncated (24-amino-acid) PB1-F2, and PB1-F2 lacking the initiating ATG in mammalian and avian cells had no effect on cell a...Continue Reading

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Citations

Jul 9, 2016·Emerging Infectious Diseases·Luca TassoniIsabella Monne
Dec 30, 2017·International Journal of Molecular Sciences·Ram P KamalIan A York
Mar 6, 2019·Therapeutic Advances in Vaccines and Immunotherapy·Ivette A Nuñez, Ted M Ross
Sep 17, 2017·Veterinary Research·Min GuXiufan Liu
Jul 18, 2020·Viruses·Gaurav Malik, Yan Zhou
Aug 16, 2021·Virus Research·Andrew J BurnhamStephan Bour

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