Abstract
ABSTRACT Cyclophilin A (CypA) is a peptidyl-prolyl isomerase that binds to the capsid protein (CA) of human immunodeficiency virus type 1 (HIV-1) and by doing so facilitates HIV-1 replication. Although CypA is incorporated into HIV-1 virions by virtue of CypA-Gag interactions that occur during virion assembly, in this study we show that the CypA-CA interaction that occurs following the entry of the viral capsid into target cells is the major determinant of CypA's effects on HIV-1 replication. Specifically, by using normal and CypA-deficient Jurkat cells, we demonstrate that the presence of CypA in the target and not the virus-producing cell enhances HIV-1 infectivity. Moreover, disruption of the CypA-CA interaction with cyclosporine A (CsA) inhibits HIV-1 infectivity only if the target cell expresses CypA. The effect of CsA on HIV-1 infection of human cells varies according to which particular cell line is used as a target, and CA mutations that confer CsA resistance and dependence exert their effects only if target cells, and not if virus-producing cells, are treated with CsA. The differential effects of CsA on HIV-1 infection in different human cells appear not to be caused by polymorphisms in the recently described retrovirus restriction factor TRIM5α. We speculate that CypA and/or CypA-related proteins affect the fate of incoming HIV-1 capsid either directly or by modulating interactions with unidentified host cell factors.
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Dates
Type | When |
---|---|
Created | 20 years, 8 months ago (Dec. 15, 2004, 10:52 p.m.) |
Deposited | 3 years, 5 months ago (March 5, 2022, 4:37 a.m.) |
Indexed | 4 months, 1 week ago (April 11, 2025, 6:49 a.m.) |
Issued | 20 years, 7 months ago (Jan. 1, 2005) |
Published | 20 years, 7 months ago (Jan. 1, 2005) |
Published Print | 20 years, 7 months ago (Jan. 1, 2005) |
@article{Hatziioannou_2005, title={Cyclophilin Interactions with Incoming Human Immunodeficiency Virus Type 1 Capsids with Opposing Effects on Infectivity in Human Cells}, volume={79}, ISSN={1098-5514}, url={http://dx.doi.org/10.1128/jvi.79.1.176-183.2005}, DOI={10.1128/jvi.79.1.176-183.2005}, number={1}, journal={Journal of Virology}, publisher={American Society for Microbiology}, author={Hatziioannou, Theodora and Perez-Caballero, David and Cowan, Simone and Bieniasz, Paul D.}, year={2005}, month=jan, pages={176–183} }