Functional characterization of Vif proteins from HIV-1 infected patients with different APOBEC3G haplotypes

Kavidha Reddy, Marcel Ooms, Michael Letko, Nigel Garrett, Viviana Simon, Thumbi Ndung'U

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Objective: The human cytidine deaminase APOBEC3G (A3G) potently restricts HIV-1 but the virus, in turn, expresses a Vif protein which degrades A3G. A natural A3G-H186R variant, common in African populations, has been associated with a more rapid AIDS disease progression, but the underlying mechanism remains unknown. We hypothesized that differences in HIV-1 Vif activity towards A3G wild type and A3G-H186R contribute to the distinct clinical AIDS manifestation. Methods: Vif variants were cloned from plasma samples of 26 South African HIV-1 subtype C infected patients, which either express wild type A3G or A3G-H186R. The Vif alleles were assessed for their ability to counteract A3G variants using western blot and single-cycle infectivity assays. Results: We obtained a total of 392 Vif sequences which displayed an amino acid sequence difference of 6.2-19.2% between patients. The intrapatient Vif diversities from patient groups A3G WT/WT, A3G WT/H186R and A3G H186R/H186R were similar. Vif variants obtained from patients expressing A3G WT/WT and A3G H186R/H186R were capable of counteracting both A3G variants with similar efficiency. However, the antiviral activity of A3G-H186R was significantly reduced in both the presence and absence of Vif, indicating that the A3G-H186R variant intrinsically exerts less antiviral activity. Conclusion: A3G wild type and A3G-H186R are equally susceptible to counteraction by Vif, regardless of whether the Vif variant was obtained from A3G WT/WT and A3G H186R/H186R patients. However, the A3G-H186R variant intrinsically displayed lower antiviral activity, which could explain the higher plasma viral loads and accelerated disease progression reported for patients expressing A3G H186R/H186R.

Original languageEnglish
Pages (from-to)1723-1729
Number of pages7
JournalAIDS
Volume30
Issue number11
DOIs
StatePublished - 17 Jul 2016

Keywords

  • APOBEC3
  • APOBEC3G
  • HIV
  • HIV-1
  • Vif
  • restriction factor
  • subtype C

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