Abstract
The virologic factors that limit the transmission of swine influenza viruses between humans are unresolved. While it has been shown that acquisition of the neuraminidase (NA) and matrix (M) gene segments from a Eurasian-lineage swine virus was required for airborne transmission of the 2009 pandemic H1N1 virus (H1N1pdm09), we show here that an arginine to lysine change in the hemagglutinin (HA) was also necessary. This change at position 149 was distal to the receptor binding site but affected virus-receptor affinity and HA dynamics, allowing the virus to replicate more efficiently in nasal turbinate epithelium and subsequently transmit between ferrets. Receptor affinity should be considered as a factor limiting swine virus spread in humans.
Highlights
The virologic factors that limit the transmission of swine influenza viruses between humans are unresolved
Introduction of the R149K mutation into the HA of North Carolina/18161/2002 (NC/02) (NC/02HA149) led to an increase in transmission to direct contact ferrets from 5/9 for the wild type NC/02 to 9/9 for the mutant virus (p = 0.014) (Fig. 1c, Supplementary Fig. S1C); the R133AK mutation had no impact on transmission and neither mutant was detected in airborne contact animals (Fig. 1c, Supplementary Fig. S2)
In this study we evaluated the contribution of an HA R149K substitution to the biological function of a representative triple reassortant swine (TRsw) virus, NC/02
Summary
The virologic factors that limit the transmission of swine influenza viruses between humans are unresolved. In attempt to understand the impact of the R149K mutation on the cooperativity between residue motion in the RBD we applied a GNM cross correlation analysis to six different H1N1 variants: A/Darwin/2001/2009 (PDB ID: 3M6S)[22], A/California/04/2009 (PDB ID: 3UBE), A/Solomon Islands/03/2006 (PDB ID: 3SM5, A/Berlin/6/2006 for HA2)[23], A/Swine/Iowa/15/30 (PDB ID: 1RVT)[24], A/South Carolina/1/18 (PDB ID: 1RUZ)[24], and A/Puerto Rico/8/34 (PDB ID: 1RU7)[24]; the former three have a lysine in position 149 while the latter three contain an arginine.
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