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Evasion from CypA- and APOBEC-mediated restrictions is insufficient for HIV-1 to efficiently grow in simian cells
- Source :
-
Microbes & Infection . Feb2009, Vol. 11 Issue 2, p164-171. 8p. - Publication Year :
- 2009
-
Abstract
- Abstract: We have recently generated a monkey cell-tropic virus termed NL-DT5R from an HIV-1 NL4-3 clone and demonstrated that both cyclophilin A (CypA)-binding loop in Gag-capsid (CA) and Vif are responsible for the species-restriction of HIV-1. In this study, we constructed 16 CypA-binding loop mutants from the HIV-1-derivative NL-DT5R, and analyzed them biologically and biochemically. The mutants displayed various multi-cycle infection potencies in cynomolgus monkey (CyM) HSC-F cells, but none of them grew significantly better than NL-DT5R. Consistently, any of the HIV-1 variants examined here did not effectively counter CyM TRIM5α as judged by single-cycle infectivity assays. Assessment of their single-cycle infectivity in simian and CyM TRIM5α-expressing feline cells in the presence of cyclosporin A (CsA) showed that intervention of CypA–CA interaction did not restore full NL-DT5R infectivity, while CsA increased infectivity of DT5R/4-3 carrying the sequence of NL4-3 CypA-binding loop up to the NL-DT5R level. Almost similar data were obtained in the experiments utilizing CypA-targeting siRNA. Together with our previous results regarding NL-DT5R, these data suggested that evasion from CypA- and APOBEC-mediated restrictions is still insufficient for HIV-1 to completely overcome the species barrier. [Copyright &y& Elsevier]
Details
- Language :
- English
- ISSN :
- 12864579
- Volume :
- 11
- Issue :
- 2
- Database :
- Academic Search Index
- Journal :
- Microbes & Infection
- Publication Type :
- Academic Journal
- Accession number :
- 36904740
- Full Text :
- https://doi.org/10.1016/j.micinf.2008.11.002