Stably expressed APOBEC3H forms a barrier for cross-species transmission of simian immunodeficiency virus of chimpanzee to humans

PLoS Pathogens

Qinyong Gu¹  Dieter Häussinger¹  Zeli Zhang¹  Carsten Münk¹  Marc de Manuel Montero²  Tomas Marques-Bonet²  Ignacio G. Bravo³ 

[1] Clinic for Gastroenterology, Hepatology, and Infectiology, Medical Faculty, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany;Institut Biologia Evolutiva (Universitat Pompeu Fabra/CSIC) ICREA, Barcelona, Spain;Laboratory MIVEGEC, UMR CNRS 5290, UM, Montpellier, France

关键词: Chimpanzees;    Haplotypes;    293T cells;    Plasmid construction;    HIV-1;    SIV;    Tubulins;    Viral replication;   

DOI  :  10.1371/journal.ppat.1006746

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

APOBEC3s (A3s) are potent restriction factors of human immunodeficiency virus type 1/simian immunodeficiency viruses (HIV-1/SIV), and can repress cross-species transmissions of lentiviruses. HIV-1 originated from a zoonotic infection of SIV of chimpanzee (SIVcpz) to humans. However, the impact of human A3s on the replication of SIVcpz remains unclear. By using novel SIVcpz reporter viruses, we identified that human APOBEC3B (A3B) and APOBEC3H (A3H) haplotype II strongly reduced the infectivity of SIVcpz, because both of them are resistant to SIVcpz Vifs. We further demonstrated that human A3H inhibited SIVcpz by deaminase dependent as well independent mechanisms. In addition, other stably expressed human A3H haplotypes and splice variants showed strong antiviral activity against SIVcpz. Moreover, most SIV and HIV lineage Vif proteins could degrade chimpanzee A3H, but no Vifs from SIVcpz and SIV of gorilla (SIVgor) lineages antagonized human A3H haplotype II. Expression of human A3H hapII in human T cells efficiently blocked the spreading replication of SIVcpz. The spreading replication of SIVcpz was also restricted by stable A3H in human PBMCs. Thus, we speculate that stably expressed human A3H protects humans against the cross-species transmission of SIVcpz and that SIVcpz spillover to humans may have started in individuals that harbor haplotypes of unstable A3H proteins.

【 授权许可】

CC BY