期刊论文详细信息
Retrovirology
Host cell species-specific effect of cyclosporine A on simian immunodeficiency virus replication
Tetsuro Matano2  Hirofumi Akari3  Natsuko Inagaki1  Tetsuya Kuwano1  Hiroshi Ishii2  Hiroaki Takeuchi4 
[1] The Institute of Medical Science, The University of Tokyo, Tokyo, Japan;AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan;Center for Human Evolution Modeling Research, Primate Research Institute, The University of Kyoto, Aichi, Japan;Department of Molecular Virology, Tokyo Medical and Dental University, Tokyo, Japan
关键词: tropism;    cyclosporine A;    cyclophilin B;    cyclophilin A;    SIV;    HIV-1;   
Others  :  1209367
DOI  :  10.1186/1742-4690-9-3
 received in 2011-08-11, accepted in 2012-01-06,  发布年份 2012
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【 摘 要 】

Background

An understanding of host cell factors that affect viral replication contributes to elucidation of the mechanism for determination of viral tropism. Cyclophilin A (CypA), a peptidyl-prolyl cis-trans isomerase (PPIase), is a host factor essential for efficient replication of human immunodeficiency virus type 1 (HIV-1) in human cells. However, the role of cyclophilins in simian immunodeficiency virus (SIV) replication has not been determined. In the present study, we examined the effect of cyclosporine A (CsA), a PPIase inhibitor, on SIV replication.

Results

SIV replication in human CEM-SS T cells was not inhibited but rather enhanced by treatment with CsA, which inhibited HIV-1 replication. CsA treatment of target human cells enhanced an early step of SIV replication. CypA overexpression enhanced the early phase of HIV-1 but not SIV replication, while CypA knock-down resulted in suppression of HIV-1 but not SIV replication in CEM-SS cells, partially explaining different sensitivities of HIV-1 and SIV replication to CsA treatment. In contrast, CsA treatment inhibited SIV replication in macaque T cells; CsA treatment of either virus producer or target cells resulted in suppression of SIV replication. SIV infection was enhanced by CypA overexpression in macaque target cells.

Conclusions

CsA treatment enhanced SIV replication in human T cells but abrogated SIV replication in macaque T cells, implying a host cell species-specific effect of CsA on SIV replication. Further analyses indicated a positive effect of CypA on SIV infection into macaque but not into human T cells. These results suggest possible contribution of CypA to the determination of SIV tropism.

【 授权许可】

   
2012 Takeuchi et al; licensee BioMed Central Ltd.

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