Abstract
Pandemic influenza A viruses can emerge from swine, an intermediate host that supports adaptation of human-preferred receptor-binding specificity by the hemagglutinin (HA) surface antigen. Other HA traits necessary for pandemic potential are poorly understood. For swine influenza viruses isolated in 2009-2016, gamma-clade viruses had less stable HA proteins (activation pH 5.5-5.9) than pandemic clade (pH 5.0-5.5). Gamma-clade viruses replicated to higher levels in mammalian cells than pandemic clade. In ferrets, a model for human adaptation, a relatively stable HA protein (pH 5.5-5.6) was necessary for efficient replication and airborne transmission. The overall airborne transmission frequency in ferrets for four isolates tested was 42%, and isolate G15 airborne transmitted 100% after selection of a variant with a stabilized HA. The results suggest swine influenza viruses containing both a stabilized HA and alpha-2,6 receptor binding in tandem pose greater pandemic risk. Increasing evidence supports adding HA stability to pre-pandemic risk assessment algorithms.
Highlights
Aside from recent bat isolates (Tong et al, 2012; Tong et al, 2013; Kandeil et al, 2019), influenza A viruses (IAVs) originate from avian species and transmit to humans directly or via other animals (Long et al, 2019b; Russell et al, 2018)
This work showed that HA proteins from pandemic-clade human and swine IAVs are relatively stable while those from swine gamma viruses are less stable
Despite replicating to higher levels in Madin-Darby canine kidney (MDCK) cells than human pandemic viruses, swine gamma viruses with unstable HA proteins were not airborne transmitted and were outgrown quickly by minor variants that contained stabilized HA proteins
Summary
Aside from recent bat isolates (Tong et al, 2012; Tong et al, 2013; Kandeil et al, 2019), influenza A viruses (IAVs) originate from avian species and transmit to humans directly or via other animals (e.g. swine) (Long et al, 2019b; Russell et al, 2018). Avian IAVs typically have HA proteins triggered at pH 5.5–6.2 while H1N1pdm isolates (2010– 2011) have been shown to trend lower at pH 5.3–5.5 (Russell et al, 2018) This suggests that avianto-human adaptation of the HA protein may include a decrease in activation pH. We hypothesized that contemporary swine viruses vary in HA stability and strains having more stable HA proteins are more likely to transmit by the airborne route in ferrets. To test this hypothesis, we measured HA activation pH for a panel of H1N1 swine gamma viruses and infected ferrets with genetically related pairs of H1N1 swine gamma viruses that differed in HA stability
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