Evaluation of the interactions of HIV-1 integrase with small ubiquitin-like             modifiers and their conjugation enzyme Ubc9.
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.
State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai 200433, PR China.
Zhihui
Z
Li
Shuwen
S
Wu
Jingjing
J
Wang
Wenjuan
W
Li
Yun
Y
Lin
Chaoneng
C
Ji
Jinglun
J
Xue
Jinzhong
J
Chen
D015870:Gene Expression; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D019427:HIV Integrase / Q000378:metabolism*; D015497:HIV-1 / Q000201:enzymology* / Q000502:physiology; D006801:Humans; D016086:Lentivirus / Q000502:physiology; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D034622:RNA Interference; D025842:SUMO-1 Protein / Q000235:genetics / Q000378:metabolism*; D025841:Small Ubiquitin-Related Modifier Proteins / Q000235:genetics / Q000378:metabolism*; D058207:Sumoylation; D020798:Two-Hybrid System Techniques; D044763:Ubiquitin-Conjugating Enzymes / Q000235:genetics / Q000378:metabolism*; D016662:Virus Integration; D000098843:Ubiquitin-Conjugating Enzyme UBC9
D025842:SUMO-1 Protein; C495501:SUMO1 protein, human; C117909:SUMO2 protein, human; D025841:Small Ubiquitin-Related Modifier Proteins; D044763:Ubiquitin-Conjugating Enzymes; D019427:HIV Integrase; D000098843:Ubiquitin-Conjugating Enzyme UBC9