Influenza a virus reassortment is strain dependent.

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 can occur when genome segments from distinct strains reassort in coinfected cells. Predicting potential genomic reassortment between influenza strains has been a long-standing 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 elusive. To address this challenge, we developed a high throughput genotyping approach to quantify reassortment among a diverse panel of human influenza virus strains encompassing two pandemics (swine and avian origin), three specific epidemics, and both circulating human subtypes A/H1N1 and A/H3N2. We found that reassortment frequency (the proportion of reassortants generated) is an emergent property of specific pairs of strains where strain identity is a predictor of reassortment frequency. We detect little evidence that antigenic subtype drives reassortment as intersubtype (H1N1xH3N2) and intrasubtype reassortment frequencies were, on average, similar. Instead, our data suggest that certain strains bias the reassortment frequency up or down, independently of the coinfecting partner. We observe that viral productivity is also an emergent property of coinfections, but uncorrelated to reassortment frequency; thus viral productivity is a separate factor affecting the total number of reassortants produced. Assortment of individual segments among progeny and pairwise segment combinations within progeny generally favored homologous combinations. These outcomes were not related to strain similarity or shared subtype but reassortment frequency was closely correlated to the proportion of both unique genotypes and 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 to realize the goal of predicting influenza virus evolution resulting from segment exchange. Author summary: Influenza A viruses are global pathogens that cause significant human morbidity and mortality through seasonal epidemics and pandemics that arise every few decades. These viruses have remained a public health threat in large part due to their high genetic variability, notably through exchange of their eight genome segments when two viruses coinfect a cell. Thus, determining the potential for genetic exchange has been an urgent goal, but has been difficult to achieve. Here we developed a novel method to quantify genetic exchange in a diverse collection of human influenza A viruses. We show that patterns of genetic exchange show strong strain-dependence, and do not necessarily track similarity between coinfecting strains or their subtype (H1N1 or H3N2). Our data support that specific strains can consistently bias genetic exchange, increasing or decreasing exchange independent of the other coinfecting strain. Our study suggests the propensity for reassortment is not evenly shared among strains and that identifying high-reassortment strains could improve pandemic preparedness or reveal new treatments. [ABSTRACT FROM AUTHOR]