Intra- and inter-host evolution of H9N2 influenza A virus in Japanese quail

Ferreri, Lucas; Geiger, Ginger; Seibert, Brittany; Obadan, Adebimpe; Rajão, Daniela S.; Pérez, Daniel R.

doi:10.1093/ve/veac001

Cited by 10 publications

(10 citation statements)

References 67 publications

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“…The duration of the window observed here (4-8 h) is in line with previous work (20,22,23,25). Competitive interactions have also been noted in the context of experiments designed to evaluate the relative fitness of two viral variants (26)(27)(28)(29)(30). Conversely, in our own prior work, we have frequently examined coinfection between wt and var viruses with well-matched fitness that are introduced simultaneously and at the same dose.…”

Section: Discussionsupporting

confidence: 85%

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

Delima

Ganti

Holmes

et al. 2022

Preprint

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When multiple viral populations propagate within the same host environment, they often shape each other's dynamics. These interactions can be positive or negative and can occur at multiple scales, from coinfection of a cell to co-circulation at a global population level. For influenza A viruses (IAVs), the delivery of multiple viral genomes to a cell substantially increases burst size. However, despite its relevance for IAV evolution through reassortment, the implications of this positive density dependence for coinfection between distinct IAVs has not been explored. Furthermore, the extent to which these interactions within the cell shape viral dynamics at the level of the host remains unclear. Here we show that, within cells, coinfecting IAVs strongly augment the replication of a focal strain, irrespective of the native host of the coinfecting IAV or its homology to the focal strain. Coinfecting viruses with a low intrinsic reliance on multiple infection offer the greatest benefit. Nevertheless, virus-virus interactions at the level of the whole host are antagonistic. This antagonism is recapitulated in cell culture when the coinfecting virus is introduced several hours prior to the focal strain or under conditions conducive to multiple rounds of viral replication. Together, these data suggest that beneficial virus-virus interactions within cells are counterbalanced by competition for susceptible cells during viral propagation through a tissue. The integration of virus-virus interactions across scales is critical in defining the outcomes of viral coinfection.

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Section: Discussionsupporting

confidence: 85%

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

Delima

Ganti

Holmes

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…Third, introduction of PA K26E was seen to improve the kinetics and yield of GFHK99 viral replication in chicken cells and eggs [ 18 ]. Fourth, GFHK99 variant viruses carrying PA K26E rapidly emerged and underwent positive selection in experimentally infected quail [ 19 ]. Thus, while GFHK99 shows a reduced need for multiple infection in avian cells compared to mammalian cells [ 7 ], there is a fitness cost of PA 26K even in avian systems.…”

Section: Discussionmentioning

confidence: 99%

Beneficial effects of cellular coinfection resolve inefficiency in influenza A virus transcription

2022

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For diverse viruses, cellular infection with single vs. multiple virions can yield distinct biological outcomes. We previously found that influenza A/guinea fowl/Hong Kong/WF10/99 (H9N2) virus (GFHK99) displays a particularly high reliance on multiple infection in mammalian cells. Here, we sought to uncover the viral processes underlying this phenotype. We found that the need for multiple infection maps to amino acid 26K of the viral PA protein. PA 26K suppresses endonuclease activity and viral transcription, specifically within cells infected at low multiplicity. In the context of the higher functioning PA 26E, inhibition of PA using baloxavir acid augments reliance on multiple infection. Together, these data suggest a model in which sub-optimal activity of the GFHK99 endonuclease results in inefficient priming of viral transcription, an insufficiency which can be overcome with the introduction of additional viral ribonucleoprotein templates to the cell. More broadly, the finding that deficiency in a core viral function is ameliorated through multiple infection suggests that the fitness effects of many viral mutations are likely to be modulated by multiplicity of infection, such that the shape of fitness landscapes varies with viral densities.

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“…Nonetheless, commonalities are apparent. In horses, dogs, pigs and quail infected experimentally with IAV strains that circulate naturally in these species, within-host nucleotide diversity was similarly low to that seen here in naturally infected pigs and in humans [22–25]. Rapid turnover of iSNVs has also been reported for multiple hosts, suggesting that the role of genetic drift in shaping within-host IAV populations is common to diverse host species [23–25].…”

Section: Discussionmentioning

confidence: 77%

Genetic drift and purifying selection shape within-host influenza A virus populations during natural swine infections

VanInsberghe,

McBride,

DaSilva

et al. 2023

Preprint

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Patterns of within-host influenza A virus (IAV) diversity and evolution have been described in natural human infections, but these patterns remain poorly characterized in non-human hosts. Elucidating these dynamics is important to better understand IAV biology and the evolutionary processes that govern spillover into humans. Here, we sampled an IAV outbreak in pigs during a week-long county fair to characterize viral diversity and evolution in this important reservoir host. Nasal wipes were collected on a daily basis from all pigs present at the fair, yielding up to 421 samples per day. Subtyping of PCR-positive samples revealed the co-circulation of H1N1 and H3N2 subtype IAVs. PCR-positive samples with robust Ct values were deep-sequenced, yielding 506 sequenced samples from a total of 253 pigs. Based on higher depth re-sequenced data from a subset of these initially sequenced samples (260 samples from 168 pigs), we characterized patterns of within-host IAV genetic diversity and evolution. We find that IAV genetic diversity in single-subtype infected pigs is low, with the majority of intra-host single nucleotide variants (iSNVs) present at frequencies of <10%. The ratio of the number of nonsynonymous to the number of synonymous iSNVs is significantly lower than under the neutral expectation, indicating that purifying selection shapes patterns of within-host viral diversity in swine. The dynamic turnover of iSNVs and their pronounced frequency changes further indicate that genetic drift also plays an important role in shaping IAV populations within pigs. Taken together, our results highlight similarities in patterns of IAV genetic diversity and evolution between humans and swine, including the role of stochastic processes in shaping within-host IAV dynamics.

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Intra- and inter-host evolution of H9N2 influenza A virus in Japanese quail

Cited by 10 publications

References 67 publications

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

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

Beneficial effects of cellular coinfection resolve inefficiency in influenza A virus transcription

Genetic drift and purifying selection shape within-host influenza A virus populations during natural swine infections

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