کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3415146 1224943 2009 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Evasion from CypA- and APOBEC-mediated restrictions is insufficient for HIV-1 to efficiently grow in simian cells
موضوعات مرتبط
علوم زیستی و بیوفناوری ایمنی شناسی و میکروب شناسی ایمونولوژی
پیش نمایش صفحه اول مقاله
Evasion from CypA- and APOBEC-mediated restrictions is insufficient for HIV-1 to efficiently grow in simian cells
چکیده انگلیسی

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.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Microbes and Infection - Volume 11, Issue 2, February 2009, Pages 164–171
نویسندگان
, , , , ,