Residue 41 of the Eurasian Avian-Like Swine Influenza A Virus Matrix Protein Modulates Virion Filament Length and Efficiency of Contact Transmission

• Type of Material: Article
• Authors: Patricia J. Campbell, Emory University; Constantinos S. Kyriakis, Emory University; Nicolle Marshall, Emory University; Suganthi Suppiah, Emory University; Jill Seladi-Schulman, Emory University; Shamika Danzy, Emory University; Anice Carmen Lowen, Emory University; John Steel, Emory University
• Language: English
• Date: 2014-07-01
• Publisher: American Society for Microbiology
• Publication Version: Final Published Version
• Copyright Statement: © 2014, American Society for Microbiology.
• Final Published Version (URL): http://dx.doi.org/10.1128/JVI.00119-14
• Title of Journal or Parent Work: Journal of Virology
• ISSN: 0022-538X
• Volume: 88
• Issue: 13
• Start Page: 7569
• End Page: 7577
• Grant/Funding Information: This work was funded by the Centers for Excellence in Influenza Research and Surveillance (CEIRS) contract number HHSN266200700006C.
• Keywords: Science & Technology; GUINEA-PIG; M SEGMENT; MORPHOLOGY; STRAINS; MORPHOGENESIS; Life Sciences & Biomedicine; M1; H1N1 VIRUS; Virology; EVOLUTION; HEMAGGLUTININ; NEURAMINIDASE; VIROLOGY
• Research Categories: Health Sciences, Immunology; Health Sciences, General; Biology, Molecular

Abstract

Position 41 of the influenza A virus matrix protein encodes a highly conserved alanine in human and avian lineages. Nonetheless, strains of the Eurasian avian-like swine (Easw) lineage contain a change at this position: position 41 of A/swine/Spain/ 53207/04 (H1N1) (SPN04) encodes a proline. To assess the impact of this naturally occurring polymorphism on viral fitness, we utilized reverse genetics to produce recombinant viruses encoding wild-type M1 41P (rSPN04-P) and consensus 41A (rSPN04-A) residues. Relative to rSPN04-A, rSPN04-P virus displayed reduced growth in vitro. In the guinea pig model, rSPN04-P was transmitted to fewer contact animals than rSPN04-A and failed to infect guinea pigs that received a low-dose inoculum. Moreover, the P41A change altered virion morphology, reducing the number and length of filamentous virions, as well as reducing the neuraminidase activity of virions. The lab-adapted human isolate, A/PR/8/34 (H1N1) (PR8), is nontransmissible in the guinea pig model, making it a useful background in which to identify certain viral factors that enhance transmissibility. We assessed transmission in the context of single-, double-, and triple-reassortant viruses between PR8 and SPN04; PR8/SPN04 M, PR8/SPN04 M+NA, and PR8/SPN04M+NA+HA, encoding either matrix 41 A or P, were generated. In each case, the virus possessing 41P transmitted less well than the corresponding 41A-encoding virus. In summary, we have identified a naturally occurring mutation in the influenza A virus matrix protein that impacts transmission efficiency and can alter virion morphology and neuraminidase activity. © 2014, American Society for Microbiology.