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

被引:5
作者
Yousefi, Maria [1 ]
Sudarsan, Arun Kumar Annan [1 ,2 ]
Gaba, Amit [1 ]
Chelico, Linda [1 ]
机构
[1] Univ Saskatchewan, Coll Med, Dept Biochem Microbiol & Immunol, Saskatoon, SK S7N 5E5, Canada
[2] Ctr Commercializat Regenerat Med CCRM, 661 Univ Ave 1002, Toronto, ON M5G 1M1, Canada
来源
VIRUSES-BASEL | 2023年 / 15卷 / 02期
基金
加拿大健康研究院;
关键词
restriction factor; HIV-1; APOBEC3; HEPATITIS-B-VIRUS; CBF-BETA; RESTRICTION; RNA; POLYMORPHISMS; HYPERMUTATION; DIMERIZATION; DEAMINATION; INHIBITION; EVOLUTION;
D O I
10.3390/v15020463
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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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页数:13
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