Moloney leukemia virus 10 (MOV10) inhibits the degradation of APOBEC3G through interference with the Vif-mediated ubiquitin-proteasome pathway

  • Retrovirology. 2017 Dec 19;14(1):56. doi: 10.1186/s12977-017-0382-1.
Cancan Chen  1  2  3 ,  Xiaocao Ma  1  2 ,  Qifei Hu  1  2 ,  Xinghua Li  4 ,  Feng Huang  1  2 ,  Junsong Zhang  1  2 ,  Ting Pan  1  2 ,  Jinyu Xia  4 ,  Chao Liu  5  6 ,  Hui Zhang  1  2
Affiliations
  • 1. Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China.
  • 2. Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China.
  • 3. Department of Pathology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China.
  • 4. Department of Infectious Diseases, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, 519000, China.
  • 5. Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China. [email protected].
  • 6. Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China. [email protected].
PMID: 29258557 DOI: 10.1186/s12977-017-0382-1
Abstract

Background: MOV10 protein has ATP-dependent 5'-3' RNA helicase activity and belongs to the UPF1p superfamily. It can inhibit human immunodeficiency virus type 1 (HIV-1) replication at multiple stages and interact with apolipoprotein-B-mRNA-editing enzyme catalytic polypeptide-like 3G (APOBEC3G or A3G), a member of the cytidine deaminase family that exerts potent inhibitory effects against HIV-1 Infection. However, HIV-1-encoded virion infectivity factor (Vif) protein specifically mediates the degradation of A3G via the ubiquitin-proteasome system (UPS).

Results: We demonstrate that MOV10 counteracts Vif-mediated degradation of A3G by inhibiting the assembly of the Vif-CBF-β-Cullin 5-ElonginB-ElonginC complex. Through interference with UPS, MOV10 enhances the level of A3G in HIV-1-infected cells and virions, and synergistically inhibits the replication and infectivity of HIV-1. In addition, the DEAG-box of MOV10 is required for inhibition of Vif-mediated A3G degradation as the DEAG-box mutant significantly loses this ability.

Conclusions: Our results demonstrate a novel mechanism involved in the anti-HIV-1 function of MOV10. Given that both MOV10 and A3G belong to the interferon Antiviral system, their synergistic inhibition of HIV-1 suggests that these proteins may play complicated roles in Antiviral functions.

Keywords
A3G; HIV-1; MOV10; Ubiquitin–proteasome system (UPS); Vif.