Influenza A Virus Superinfection Potential Is Regulated by Viral Genomic Heterogeneity

ABSTRACT Defining the specific factors that govern the evolution and transmission of influenza A virus (IAV) populations is of critical importance for designing more-effective prediction and control strategies. Superinfection, the sequential infection of a single cell by two or more virions, plays a...

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Autores principales: Jiayi Sun, Christopher B. Brooke
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Publicado: American Society for Microbiology 2018
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spelling oai:doaj.org-article:54e0ee17e2614637ae180f35073a672b2021-11-15T15:58:20ZInfluenza A Virus Superinfection Potential Is Regulated by Viral Genomic Heterogeneity10.1128/mBio.01761-182150-7511https://doaj.org/article/54e0ee17e2614637ae180f35073a672b2018-11-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01761-18https://doaj.org/toc/2150-7511ABSTRACT Defining the specific factors that govern the evolution and transmission of influenza A virus (IAV) populations is of critical importance for designing more-effective prediction and control strategies. Superinfection, the sequential infection of a single cell by two or more virions, plays an important role in determining the replicative and evolutionary potential of IAV populations. The prevalence of superinfection during natural infection and the specific mechanisms that regulate it remain poorly understood. Here, we used a novel single virion infection approach to directly assess the effects of individual IAV genes on superinfection efficiency. Rather than implicating a specific viral gene, this approach revealed that superinfection susceptibility is determined by the total number of viral gene segments expressed within a cell. IAV particles that express a complete set of viral genes potently inhibit superinfection, while semi-infectious particles (SIPs) that express incomplete subsets of viral genes do not. As a result, virus populations that contain more SIPs undergo more-frequent superinfection. We further demonstrate that viral replicase activity is responsible for inhibiting subsequent infection. These findings identify both a major determinant of IAV superinfection potential and a prominent role for SIPs in promoting viral coinfection. IMPORTANCE Superinfection, the sequential infection of a single cell by two or more virions, plays an important role in determining the replicative and evolutionary potential of influenza A virus (IAV) populations. The specific mechanisms that regulate superinfection during natural infection remain poorly understood. Here, we show that superinfection susceptibility is determined by the total number of viral genes expressed within a cell and is independent of their specific identity. Virions that express a complete set of viral genes potently inhibit superinfection, while the semi-infectious particles (SIPs) that make up the bulk of IAV populations and express incomplete subsets of viral genes do not. As a result, viral populations with more SIPs undergo more-frequent superinfection. These findings identify both the primary determinant of IAV superinfection potential and a prominent role for SIPs in promoting coinfection.Jiayi SunChristopher B. BrookeAmerican Society for MicrobiologyarticlecoinfectioninfluenzasuperinfectionvirusMicrobiologyQR1-502ENmBio, Vol 9, Iss 5 (2018)
institution DOAJ
collection DOAJ
language EN
topic coinfection
influenza
superinfection
virus
Microbiology
QR1-502
spellingShingle coinfection
influenza
superinfection
virus
Microbiology
QR1-502
Jiayi Sun
Christopher B. Brooke
Influenza A Virus Superinfection Potential Is Regulated by Viral Genomic Heterogeneity
description ABSTRACT Defining the specific factors that govern the evolution and transmission of influenza A virus (IAV) populations is of critical importance for designing more-effective prediction and control strategies. Superinfection, the sequential infection of a single cell by two or more virions, plays an important role in determining the replicative and evolutionary potential of IAV populations. The prevalence of superinfection during natural infection and the specific mechanisms that regulate it remain poorly understood. Here, we used a novel single virion infection approach to directly assess the effects of individual IAV genes on superinfection efficiency. Rather than implicating a specific viral gene, this approach revealed that superinfection susceptibility is determined by the total number of viral gene segments expressed within a cell. IAV particles that express a complete set of viral genes potently inhibit superinfection, while semi-infectious particles (SIPs) that express incomplete subsets of viral genes do not. As a result, virus populations that contain more SIPs undergo more-frequent superinfection. We further demonstrate that viral replicase activity is responsible for inhibiting subsequent infection. These findings identify both a major determinant of IAV superinfection potential and a prominent role for SIPs in promoting viral coinfection. IMPORTANCE Superinfection, the sequential infection of a single cell by two or more virions, plays an important role in determining the replicative and evolutionary potential of influenza A virus (IAV) populations. The specific mechanisms that regulate superinfection during natural infection remain poorly understood. Here, we show that superinfection susceptibility is determined by the total number of viral genes expressed within a cell and is independent of their specific identity. Virions that express a complete set of viral genes potently inhibit superinfection, while the semi-infectious particles (SIPs) that make up the bulk of IAV populations and express incomplete subsets of viral genes do not. As a result, viral populations with more SIPs undergo more-frequent superinfection. These findings identify both the primary determinant of IAV superinfection potential and a prominent role for SIPs in promoting coinfection.
format article
author Jiayi Sun
Christopher B. Brooke
author_facet Jiayi Sun
Christopher B. Brooke
author_sort Jiayi Sun
title Influenza A Virus Superinfection Potential Is Regulated by Viral Genomic Heterogeneity
title_short Influenza A Virus Superinfection Potential Is Regulated by Viral Genomic Heterogeneity
title_full Influenza A Virus Superinfection Potential Is Regulated by Viral Genomic Heterogeneity
title_fullStr Influenza A Virus Superinfection Potential Is Regulated by Viral Genomic Heterogeneity
title_full_unstemmed Influenza A Virus Superinfection Potential Is Regulated by Viral Genomic Heterogeneity
title_sort influenza a virus superinfection potential is regulated by viral genomic heterogeneity
publisher American Society for Microbiology
publishDate 2018
url https://doaj.org/article/54e0ee17e2614637ae180f35073a672b
work_keys_str_mv AT jiayisun influenzaavirussuperinfectionpotentialisregulatedbyviralgenomicheterogeneity
AT christopherbbrooke influenzaavirussuperinfectionpotentialisregulatedbyviralgenomicheterogeneity
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