Natural Polymorphisms in Human APOBEC3H and HIV-1 Vif Combine in Primary T Lymphocytes to Affect Viral G-to-A Mutation Levels and Infectivity

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The APOBEC3 enzymes protect cells by inhibiting the spread of retroelements, including HIV-1, by blocking reverse transcription and mutating cytosines in single-stranded DNA replication intermediates. HIV-1 Vif counteracts restriction by marking APOBEC3 proteins for proteasomal degradation. APOBEC3H is the most diverse member of this protein family. Humans have seven distinct APOBEC3H haplotypes with three producing stable and four producing unstable proteins upon forced overexpression. Here, we examine the stability phenotype of endogenous APOBEC3H in donors with different haplotypes and address how these stability differences, as well as natural viral diversity, combine to determine HIV-1 infectivity. We found that endogenous APOBEC3H haplotypes yield stable or unstable proteins and that stable APOBEC3H is induced during viral infection and restricts the replication of isolates with naturally occurring hypo-functional but not hyper-functional Vif alleles. We also found that the global distribution of stable APOBEC3H alleles correlates with the prevalence of HIV-1 Vif alleles capable of mediating its degradation, strongly suggesting that the viral Vif protein is capable of adapting to the APOBEC3H restriction potential of an infected individual. Thus, the combination of human APOBEC3H haplotypes and virus Vif alleles may help account for some of the observed disparities in disease progression and virus transmission.

Vyšlo v časopise: Natural Polymorphisms in Human APOBEC3H and HIV-1 Vif Combine in Primary T Lymphocytes to Affect Viral G-to-A Mutation Levels and Infectivity. PLoS Genet 10(11): e32767. doi:10.1371/journal.pgen.1004761
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004761

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