Evasion from CypA- and APOBEC-mediated restrictions is insufficient for HIV-1 to efficiently grow in simian cells.
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 TRIM5alpha as judged by single-cycle infectivity assays. Assessment of their single-cycle infectivity in simian and CyM TRIM5alpha-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.
Kamada
Kazuya
K
Department of Virology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8503, Japan.
Yamashita
Tomoki
T
Hatcho
Kazuki
K
Adachi
Akio
A
Nomaguchi
Masako
M
D000071479:APOBEC-1 Deaminase; D000818:Animals; D002415:Cats; D002460:Cell Line; D002522:Chlorocebus aethiops; D021984:Cyclophilin A / Q000235:genetics / Q000276:immunology*; D003564:Cytidine Deaminase / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000254:growth & development* / Q000276:immunology; D006801:Humans; D008252:Macaca fascicularis; D008969:Molecular Sequence Data
D000071479:APOBEC-1 Deaminase; C000605089:APOBEC1 protein, human; D003564:Cytidine Deaminase; D021984:Cyclophilin A