Stability of APOBEC3F in the Presence of the APOBEC3 Antagonist HIV-1 Vif Increases at the Expense of Co-Expressed APOBEC3H Haplotype I.

Viruses

Department of Biochemistry, Microbiology, and Immunology, College of Medicine, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada.

Published: February 2023

AI Article Synopsis

  • The seven APOBEC3 enzymes serve as host restriction factors that can limit HIV-1 replication, with varying effectiveness among them.
  • The HIV-1 Vif protein hinders APOBEC3 activity by promoting their degradation through the proteasome, but certain APOBEC3 enzymes can form complexes that enhance their resistance to Vif.
  • The study found that while APOBEC3F, APOBEC3C, and APOBEC3G can interact with APOBEC3H haplotype I, only APOBEC3F led to an increase in its degradation and ultimately boosted the restriction of HIV-1 in the presence of Vif.

Article Abstract

The seven human APOBEC3 enzymes (APOBEC3A through H, excluding E) are host restriction factors. Most of the APOBEC3 enzymes can restrict HIV-1 replication with different efficiencies. The HIV-1 Vif protein combats APOBEC3-mediated restriction by inducing ubiquitination and degradation in the proteasome. APOBEC3F and APOBEC3G can hetero-oligomerize, which increases their restriction capacity and resistance to Vif. Here we determined if APOBEC3C, APOBEC3F, or APOBEC3G could hetero-oligomerize with APOBEC3H haplotype I. APOBEC3H haplotype I has a short half-life in cells due to ubiquitination and degradation by host proteins, but is also resistant to Vif. We hypothesized that hetero-oligomerization with APOBEC3H haplotype I may result in less Vif-mediated degradation of the interacting APOBEC3 and stabilize APOBEC3H haplotype I, resulting in more efficient HIV-1 restriction. Although we found that all three APOBEC3s could interact with APOBEC3H haplotype I, only APOBEC3F affected APOBEC3H haplotype I by surprisingly accelerating its proteasomal degradation. However, this increased APOBEC3F levels in cells and virions in the absence or presence of Vif and enabled APOBEC3F-mediated restriction of HIV-1 in the presence of Vif. Altogether, the data suggest that APOBEC3 enzymes can co-regulate each other at the protein level and that they cooperate to ensure HIV-1 inactivation rather than evolution.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9960753PMC
http://dx.doi.org/10.3390/v15020463DOI Listing

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