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Nat Commun ; 10(1): 3526, 2019 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-31387995

RESUMO

Segmentation of viral genomes into multiple RNAs creates the potential for replication of incomplete viral genomes (IVGs). Here we use a single-cell approach to quantify influenza A virus IVGs and examine their fitness implications. We find that each segment of influenza A/Panama/2007/99 (H3N2) virus has a 58% probability of being replicated in a cell infected with a single virion. Theoretical methods predict that IVGs carry high costs in a well-mixed system, as 3.6 virions are required for replication of a full genome. Spatial structure is predicted to mitigate these costs, however, and experimental manipulations of spatial structure indicate that local spread facilitates complementation. A virus entirely dependent on co-infection was used to assess relevance of IVGs in vivo. This virus grows robustly in guinea pigs, but is less infectious and does not transmit. Thus, co-infection allows IVGs to contribute to within-host spread, but complete genomes may be critical for transmission.


Assuntos
Vírus Defeituosos/patogenicidade , Genoma Viral , Vírus da Influenza A Subtipo H3N2/patogenicidade , Influenza Humana/transmissão , Replicação Viral/genética , Animais , Vírus Defeituosos/genética , Modelos Animais de Doenças , Cães , Evolução Molecular , Feminino , Cobaias , Células HEK293 , Humanos , Vírus da Influenza A Subtipo H3N2/genética , Influenza Humana/virologia , Funções Verossimilhança , Células Madin Darby de Rim Canino , Modelos Biológicos , RNA Viral/genética , Análise de Célula Única , Carga Viral , Vírion/genética , Eliminação de Partículas Virais/genética
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