Influenza A virus reassortment is strain dependent

Abstract

RNA viruses can exchange genetic material during coinfection, an interaction that creates novel strains with implications for viral evolution and public health. Influenza A viral genetic exchange occurs when genome segments from distinct strains reassort in coinfection. Predicting potential reassortment between influenza strains is a longstanding goal. Experimental coinfection studies have shed light on factors that limit or promote reassortment. However, determining the reassortment potential between diverse Influenza A strains has remained an elusive goal. To fill this gap, we developed a high throughput genotyping approach to quantify reassortment among a diverse panel of human influenza virus strains, encompassing 41 years of epidemics, multiple geographic locations, and both circulating human subtypes A/H1N1 and A/H3N2. We found that the reassortment rate (proportion of reassortants) is an emergent property of a pair of strains where strain identity is a predictor of the reassortment rate. We show little evidence that antigenic subtype drives reassortment as intersubtype (H1N1xH3N2) and intrasubtype reassortment rates were, on average, similar. Instead, our data suggest that certain strains bias the reassortment rate up or down, independently of the coinfecting partner. We also observe that viral productivity is an emergent property of coinfections and that it is not correlated to reassortment rate, thus affecting the total number of reassortant progeny produced. Assortment of individual segments among progeny, and pairwise segment combinations within progeny, were not random and generally favored homologous combinations. This outcome was not related to strain similarity or shared subtype. Reassortment rate was closely correlated to both the proportion of unique genotypes and the proportion of progeny with heterologous pairwise segment combinations. We provide experimental evidence that viral genetic exchange is potentially an individual social trait subject to natural selection, which implies the propensity for reassortment is not evenly shared among strains. This study highlights the need for research incorporating diverse strains to discover the traits that shift the reassortment potential as we work towards the goal of predicting influenza virus evolution resulting from segment exchange.