A Variant Macaque-Tropic Human Immunodeficiency Virus Type 1 Is Resistant to Alpha Interferon-Induced Restriction in Pig-Tailed Macaque CD4+ T Cells

摘要: Human immunodeficiency virus type 1 (HIV-1) antagonizes innate restriction factors in order to infect and persistently replicate a host. In previous study, we demonstrated that HIV-1 NL4-3 with simian mne (SIVmne) vif gene substitution (HSIV-vif-NL4-3) could pig-tailed macaques (PTM), indicating APOBEC3 proteins are primary barriers transmission. Because viral replication was persistent but low, hypothesized HSIV-vif-NL4-3 may be suppressed by I interferons (IFN-I), which known upregulate the expression of factors. Here, demonstrate IFN-α more potently suppresses PTM CD4(+) T cells than it does pathogenic SIVmne027. Importantly, identify variant (HSIV-vif-Yu2) is resistant IFN-α, IFN-α-induced barrier can overcome HSIV-vif chimeras cells. Interestingly, HSIV-vif-Yu2 similarly restricted BST2/Tetherin, neither downregulates from surface infected Resistance appears conferred determinant includes env su. Finally, show Yu-2 su allele an entry. Together, our data prototype macaque-tropic clones based on not sufficiently antagonize However, variants resistance enhance overcoming early cycle.