Evaluation of the interactions of HIV-1 integrase with small ubiquitin-like modifiers and their conjugation enzyme Ubc9

Li,Zhihui; Wu,Shuwen; Wang,Jingjing; Li,Wenjuan; Lin,Yun; Ji,Chaoneng; Xue,Jinglun; Chen,Jinzhong

doi:10.3892/ijmm.2012.1088

Evaluation of the interactions of HIV-1 integrase with small ubiquitin-like modifiers and their conjugation enzyme Ubc9

Authors:
- Zhihui Li
- Shuwen Wu
- Jingjing Wang
- Wenjuan Li
- Yun Lin
- Chaoneng Ji
- Jinglun Xue
- Jinzhong Chen
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Affiliations: State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200433, P.R. China, Modern Virology Research Center, State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, P.R. China
Published online on: August 8, 2012 https://doi.org/10.3892/ijmm.2012.1088
Pages: 1053-1060

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Abstract

Human immunodeficiency virus type 1 (HIV-1) integrase mediates the integration of reverse-transcribed viral cDNA into the genome of the host for the stable maintenance of the viral genome and the persistence of HIV-1 infection. In this study, the relationships between HIV-1 integrase (HIV-1 IN) and three SUMO conjugation pathway proteins, as well as the effects of these associations, were investigated. The overexpression of SUMO1/SUMO2 and Ubc9 changed the intracellular localization of HIV-1 IN from a diffuse distribution to a punctate localization. SUMO1, SUMO2 and Ubc9 were shown to interact with HIV-1 IN. The SUMOylation of HIV-1 IN was verified. In addition, SUMO1, SUMO2 and Ubc9 were shown to influence the integration of both lentivirus and HIV-1. The overexpression of Ubc9 inhibited viral genome integration, and the upregulation of SUMO1 or SUMO2 enhanced the inhibitory effect of Ubc9. Knockdown of the endogenous levels of SUMO1, SUMO2 and Ubc9 increased the level of viral integration, while reverse transcription and the nuclear import of preintegration complex (PIC) were not affected. Our findings suggest that SUMO conjugation pathway proteins may act as cellular restriction factors and be detrimental to HIV-1 infection. These findings merit further investigation because of their potentially significant implications for the cellular antiviral response to HIV-1 infection.

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