Thursday, October 27, 2022

When viruses cohabit: Flu + RSV = Hybrid Frankenvirus

Experts worry that this winter might be made miserable by unwelcome visitors: something new, coronavirus variants, something flu (influenza A virus, IAV) and something blew, respiratory syncytial virus (RSV). What happens when somebody hosts IAV and RSV at the same time?

These investigators infected cultured human lung cells, A549 cells, and confirmed previous reports that coinfection reduces RSV but not IAV replication (Fig 1). Despite producing lower titer, they observed that infection with IAV appeared to increase the rate of coinfection by RSV.

Fig 3b. Filament with features of IAV and RSV.

IAV and RSV are enveloped viruses that bud from the cell membrane with characteristic glycoproteins hemagglutinin (HA) and fusion (F), respectively. Having detected HA in areas of RSV budding from coinfected cells, the authors hypothesized that some virions would contain components of both viruses. Indeed, they observed many filaments, typical of RSV, with proteins from both viruses, albeit segregated (Fig 2a-e). A remarkable scanning electron micrograph appears to show hybrid viral particles (HVP) budding from the filaments (2f, red arrows). They analyzed the hybrid buds using cryo-ET and were able to ‘segment’ features of both viruses (shown, Fig 3b): mostly IAV virions budding from mostly RSV filaments. 

Amazing biology, but what does it mean clinically? The authors found that the hybrid virions contained IAV capable of infecting cells that had been depleted of their sialic acids, which bind HA, by treatment with neuraminidase (NA), Fig. 4-5). This could be an important mechanism widening the range of infected cells.

Haney J, Vijayakrishnan S, Streetley J, Dee K, Goldfarb DM, Clarke M, Mullin M, Carter SD, Bhella D, Murcia PR. Coinfection by influenza A virus and respiratory syncytial virus produces hybrid virus particlesNat Microbiol. 2022 Oct 24. doi: 10.1038/s41564-022-01242-5. Epub ahead of print. PMID: 36280786.

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