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APOBEC3D and APOBEC3F Potently Promote HIV-1 Diversification and Evolution in Humanized Mouse Model


Mutation can produce three outcomes in viruses:
detrimental, neutral, or beneficial. The first one leads to abrogation of virus replication because of error catastrophe, while the last one lets the virus escape from anti-viral immune system or adapt to the host. Human APOBEC3D, APOBEC3F, and APOBEC3G are cellular cytidine deaminases which cause G-to-A mutations in HIV-1 genome. Here we use a humanized mouse model and demonstrate that endogenous APOBEC3F and APOBEC3G induce G-to-A hypermutation in viral genomes and exert strong anti-HIV-1 activity in vivo. We also reveal that endogenous APOBEC3D and/or APOBEC3F induce viral diversification, which can lead to the emergence of a mutated virus that converts its coreceptor usage. Our results suggest that APOBEC3D and APOBEC3F are capable of promoting viral diversification and functional evolution in vivo.


Vyšlo v časopise: APOBEC3D and APOBEC3F Potently Promote HIV-1 Diversification and Evolution in Humanized Mouse Model. PLoS Pathog 10(10): e32767. doi:10.1371/journal.ppat.1004453
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004453

Souhrn

Mutation can produce three outcomes in viruses:
detrimental, neutral, or beneficial. The first one leads to abrogation of virus replication because of error catastrophe, while the last one lets the virus escape from anti-viral immune system or adapt to the host. Human APOBEC3D, APOBEC3F, and APOBEC3G are cellular cytidine deaminases which cause G-to-A mutations in HIV-1 genome. Here we use a humanized mouse model and demonstrate that endogenous APOBEC3F and APOBEC3G induce G-to-A hypermutation in viral genomes and exert strong anti-HIV-1 activity in vivo. We also reveal that endogenous APOBEC3D and/or APOBEC3F induce viral diversification, which can lead to the emergence of a mutated virus that converts its coreceptor usage. Our results suggest that APOBEC3D and APOBEC3F are capable of promoting viral diversification and functional evolution in vivo.


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Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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