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.
机构:
Mt Sinai Sch Med, Dept Microbiol, New York, NY 10029 USAMt Sinai Sch Med, Dept Microbiol, New York, NY 10029 USA
Binka, Mawuena
Ooms, Marcel
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Mt Sinai Sch Med, Dept Microbiol, New York, NY 10029 USAMt Sinai Sch Med, Dept Microbiol, New York, NY 10029 USA
Ooms, Marcel
Steward, Myeika
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Mt Sinai Sch Med, Dept Microbiol, New York, NY 10029 USAMt Sinai Sch Med, Dept Microbiol, New York, NY 10029 USA
Steward, Myeika
Simon, Viviana
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Mt Sinai Sch Med, Dept Microbiol, New York, NY 10029 USA
Mt Sinai Sch Med, Global Hlth & Emerging Pathogens Inst, New York, NY USA
Mt Sinai Sch Med, Dept Med, Div Infect Dis, New York, NY USAMt Sinai Sch Med, Dept Microbiol, New York, NY 10029 USA
机构:
NCI, Viral Mutat Sect, HIV Drug Resistance Program, Ctr Canc Res, Frederick, MD 21702 USANCI, Viral Mutat Sect, HIV Drug Resistance Program, Ctr Canc Res, Frederick, MD 21702 USA
Smith, Jessica L.
Pathak, Vinay K.
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NCI, Viral Mutat Sect, HIV Drug Resistance Program, Ctr Canc Res, Frederick, MD 21702 USANCI, Viral Mutat Sect, HIV Drug Resistance Program, Ctr Canc Res, Frederick, MD 21702 USA
机构:
Icahn Sch Med Mt Sinai, Dept Microbiol, New York, NY 10029 USAIcahn Sch Med Mt Sinai, Dept Microbiol, New York, NY 10029 USA
Ooms, Marcel
Brayton, Bonnie
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机构:
Univ Hawaii Manoa, Hawaii Ctr AIDS, John A Burns Sch Med, Dept Trop Med Med Microbiol & Pharmacol,Immunol &, Honolulu, HI 96813 USAIcahn Sch Med Mt Sinai, Dept Microbiol, New York, NY 10029 USA
Brayton, Bonnie
Letko, Michael
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Icahn Sch Med Mt Sinai, Dept Microbiol, New York, NY 10029 USAIcahn Sch Med Mt Sinai, Dept Microbiol, New York, NY 10029 USA
Letko, Michael
Maio, Susan M.
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Icahn Sch Med Mt Sinai, Dept Microbiol, New York, NY 10029 USAIcahn Sch Med Mt Sinai, Dept Microbiol, New York, NY 10029 USA
Maio, Susan M.
Pilcher, Christopher D.
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Univ Calif San Francisco, Dept Med, Div HIV AIDS, San Francisco, CA 94105 USAIcahn Sch Med Mt Sinai, Dept Microbiol, New York, NY 10029 USA
Pilcher, Christopher D.
Hecht, Frederick M.
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Univ Calif San Francisco, Dept Med, Div HIV AIDS, San Francisco, CA 94105 USAIcahn Sch Med Mt Sinai, Dept Microbiol, New York, NY 10029 USA
Hecht, Frederick M.
Barbour, Jason D.
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Univ Hawaii Manoa, Hawaii Ctr AIDS, John A Burns Sch Med, Dept Trop Med Med Microbiol & Pharmacol,Immunol &, Honolulu, HI 96813 USAIcahn Sch Med Mt Sinai, Dept Microbiol, New York, NY 10029 USA
Barbour, Jason D.
Simon, Viviana
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Icahn Sch Med Mt Sinai, Dept Microbiol, New York, NY 10029 USA
Icahn Sch Med Mt Sinai, Global Hlth & Emerging Pathogens Inst, New York, NY 10029 USA
Icahn Sch Med Mt Sinai, Dept Med, Div Infect Dis, New York, NY 10029 USAIcahn Sch Med Mt Sinai, Dept Microbiol, New York, NY 10029 USA
机构:
Icahn Sch Med Mt Sinai, Dept Microbiol, New York, NY 10029 USAIcahn Sch Med Mt Sinai, Dept Microbiol, New York, NY 10029 USA
Ooms, Marcel
Letko, Michael
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机构:
Icahn Sch Med Mt Sinai, Dept Microbiol, New York, NY 10029 USA
Icahn Sch Med Mt Sinai, Grad Sch Biomed Sci, New York, NY 10029 USA
NIAID, Virol Lab, Div Intramural Res, NIH,Rocky Mt Labs, Hamilton, MT USAIcahn Sch Med Mt Sinai, Dept Microbiol, New York, NY 10029 USA
Letko, Michael
Simon, Viviana
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机构:
Icahn Sch Med Mt Sinai, Dept Microbiol, New York, NY 10029 USA
Icahn Sch Med Mt Sinai, Global Hlth & Emerging Pathogens Inst, New York, NY 10029 USA
Icahn Sch Med Mt Sinai, Dept Med, Div Infect Dis, New York, NY 10029 USAIcahn Sch Med Mt Sinai, Dept Microbiol, New York, NY 10029 USA