Influenza A virus reassortment in mammals gives rise to genetically distinct within-host sub-populations

Abstract

Influenza A virus (IAV) genetic exchange through reassortment has the potential to accelerate viral evolution and has played a critical role in the generation of multiple pandemic strains. For reassortment to occur, distinct viruses must co-infect the same cell. The spatio-temporal dynamics of viral dissemination within an infected host therefore define opportunity for reassortment. Here, we used wild type and synonymously barcoded variant viruses of a pandemic H1N1 strain to examine the within-host viral dynamics that govern reassortment in guinea pigs, ferrets and swine. The first two species are well-established models of human influenza, while swine are a natural host and a frequent conduit for cross-species transmission and reassortment. Our results show reassortment to be pervasive in all three hosts but less frequent in swine than in ferrets and guinea pigs. In ferrets, tissue-specific differences in the opportunity for reassortment are also evident, with more reassortants detected in the nasal tract than the lower respiratory tract. While temporal trends in viral diversity are limited, spatial patterns are clear, with heterogeneity in the viral genotypes detected at distinct anatomical sites revealing extensive compartmentalization of reassortment and replication. Our data indicate that the dynamics of viral replication in mammals allow diversification through reassortment but that the spatial compartmentalization of variants likely shapes their evolution and onward transmission.

The Origin of Internal Genes Contributes to the Replication and Transmission Fitness of H7N9 Avian Influenza Virus

“…However, the effect of the bottle neck may vary, depending on species and transmission route ( 45 ). In avian hosts, the replication and dissemination of progeny AIV occurs via both the respiratory and enteric tracts, suggesting that two anatomically separate bottle necks may function simultaneously in infected birds as has been hypothesized previously ( 46 , 47 ).…”

Influenza A virus coinfection dynamics are shaped by distinct virus-virus interactions within and between cells

“…In addition, cellular coinfection can augment viral yield from productively infected cells by increasing the efficiency of core viral processes (17). Localized viral spread yields areas of high MOI, providing ample opportunity for coinfection, complementation and enhanced replication (15,21). At the within-host scale, our data reveal a competitive effect wherein the virus introduced at a higher dose or an earlier time point suppresses the replication of the other.…”

“…In addition, cellular coinfection can augment viral yield from productively infected cells by increasing the efficiency of core viral processes (17). Localized viral spread yields areas of high MOI, providing ample opportunity for coinfection, complementation and enhanced replication (15, 21).…”

Rapid transmission and tight bottlenecks constrain the evolution of highly transmissible SARS-CoV-2 variants

“…However, we found that all transmission pairs had equal bottlenecks even when we tested mutually exclusive transmission pairs. Second, virus populations may be spatially segregated within hosts, and the transmitted population may not have been well sampled by our analysis of nasal swabs (49)(50)(51)(52)(53). However, given the low viral diversity identified in nearly all cases, even spatially segregated viral populations are likely to be genetically similar to each other.…”