Host cell species-specific effect of cyclosporine A on simian immunodeficiency virus replication

Hiroaki Takeuchi,Hirofumi Akari,Natsuko Inagaki,Tetsuya Kuwano,Tetsuro Matano,Hiroshi Ishii

doi:10.1186/1742-4690-9-3

Abstract

BackgroundAn 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.ResultsSIV 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.ConclusionsCsA 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.

Highlights

An understanding of host cell factors that affect viral replication contributes to elucidation of the mechanism for determination of viral tropism
Effect of cyclosporine A (CsA) treatment on simian immunodeficiency virus (SIV) replication in human T cells We investigated the effect of CsA treatment on wild-type SIV replication in human CEM-SS T cells
Consistent with previous reports, CsA treatment inhibited the packaging of Cyclophilin A (CypA) into human immunodeficiency virus type 1 (HIV-1) particles (Figure 1B) and impaired HIV-1 replication in CEM-SS cells (Figure 1A)

Summary

Introduction

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. The role of cyclophilins in simian immunodeficiency virus (SIV) replication has not been determined. Viral replication is modulated by host cell factors, with the species specificity of these factors affecting viral tropism. The anti-viral systems mediated by such host restriction factors, termed intrinsic immunity, play an important role in determining species-specific barriers against viral infection. Cyclophilin A (CypA), a peptidyl-prolyl isomerase, is a host cell factor essential for efficient HIV-1 replication in human cells [13,14,15,16,17,18,19]. Interaction of viral CA with CypA in target cells after viral entry has been shown to promote HIV-1

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