Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
J Virol. 2012 Apr;86(8):4708-14. doi: 10.1128/JVI.05887-11. Epub 2012 Feb 1.
The antiviral factor CPSF6-358 interferes with the nuclear entry of human immunodeficiency virus type 1 (HIV-1). HIV-1 acquires resistance to CPSF6-358 through the N74D mutation of the capsid (CA), which alters its nuclear entry pathway. Here we show that compared to wild-type (WT) HIV-1, N74D HIV-1 is more sensitive to cyclosporine, has increased sensitivity to nevirapine, and is impaired in macrophage infection prior to reverse transcription. These phenotypes suggest a difference in the N74D reverse transcription complex that manifests early after infection and prior to interaction with the nuclear pore. Overall, our data indicate that N74D HIV-1 replication in transformed cells requires cyclophilin A but is dependent on other interactions in macrophages.
抗病毒因子 CPSF6-358 干扰了人类免疫缺陷病毒 1 型（HIV-1）的核内进入。HIV-1 通过衣壳（CA）的 N74D 突变获得对 CPSF6-358 的抗性，从而改变其核内进入途径。在这里，我们表明与野生型（WT）HIV-1 相比，N74D HIV-1 对环孢菌素更敏感，对奈韦拉平更敏感，并且在逆转录之前感染巨噬细胞的能力受损。这些表型表明在感染后早期和与核孔相互作用之前，N74D 逆转录复合物存在差异。总的来说，我们的数据表明，转化细胞中的 N74D HIV-1 复制需要亲环素 A，但在巨噬细胞中还依赖于其他相互作用。
