期刊
AIDS RESEARCH AND HUMAN RETROVIRUSES
卷 28, 期 8, 页码 913-922出版社
MARY ANN LIEBERT, INC
DOI: 10.1089/aid.2011.0180
关键词
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资金
- Japan Human Science Foundation
- Japanese Ministry of Health, Labor and Welfare (Research on HIV/AIDS)
- Japanese Ministry of Education, Culture, Sports, Science and Technology (Priority Areas Matrix of Infection Phenomena) [18073008]
- Grants-in-Aid for Scientific Research [18073008, 22790430, 23659229, 23790500, 24115008, 21390137] Funding Source: KAKEN
Rho GTPases are able to influence the replication of human immunodeficiency virus type 1 (HIV-1). However, little is known about the regulation of HIV-1 replication by guanine nucleotide dissociation inhibitors (GDIs), one of the three major regulators of the Rho GTPase activation cycle. From a T cell-based cDNA library screening, ARHGDIB/RhoGDI beta, a hematopoietic lineage-specific GDI family protein, was identified as a negative regulator of HIV-1 replication. Up-regulation of ARHGDIB attenuated the replication of HIV-1 in multiple T cell lines. The results showed that (1) a significant portion of RhoA and Rac1, but not Cdc42, exists in the GTP-bound active form under steady-state conditions, (2) ectopic ARHGDIB expression reduced the F-actin content and the active forms of both RhoA and Rac1, and (3) HIV-1 infection was attenuated by either ectopic expression of ARHGDIB or inhibition of the RhoA signal cascade at the HIV-1 Env-dependent early phase of the viral life cycle. This is in good agreement with the previous finding that RhoA and Rac1 promote HIV-1 entry by increasing the efficiency of receptor clustering and virus-cell membrane fusion. In conclusion, the ARHGDIB is a lymphoid-specific intrinsic negative regulator of HIV-1 replication that acts by simultaneously inhibiting RhoA and Rac1 functions.
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