Poli G, Orenstein J M, Kinter A, Folks T M, Fauci A S
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892.
Science. 1989 May 5;244(4904):575-7. doi: 10.1126/science.2470148.
Promonocytic (U1) and T lymphocytic (ACH-2) cell lines chronically infected with human immunodeficiency virus type 1 (HIV-1) constitutively express low levels of virus, but expression can be induced by phorbol esters and cytokines. Whereas ACH-2 cells produce infectious virions, U1 cells produce defective, noninfectious particles. Although 3'-azido-3'-deoxythimidine (AZT) prevented acute HIV infection of susceptible cells, it did not prevent the induction of HIV expression in the infected cell lines. In contrast, interferon alpha (IFN-alpha) inhibited the release of reverse transcriptase and viral antigens into the culture supernatant after phorbol ester stimulation of both cell lines. Further, IFN-alpha suppressed the production or release (or both) of whole HIV virions, but had no effect on the amount of cell-associated viral proteins. Also, after phorbol ester stimulation of ACH-2 cells, IFN-alpha reduced the number of infectious viral particles secreted into the culture supernatant, but had no effect on the infectivity of cell-associated virus. These findings lend support to the combined use of antiviral agents that have action at both the early (AZT) and the late (IFN-alpha) stages of HIV replication.
持续感染1型人类免疫缺陷病毒（HIV-1）的单核细胞系（U1）和T淋巴细胞系（ACH-2）组成性表达低水平病毒，但佛波酯和细胞因子可诱导其表达。ACH-2细胞产生有感染性的病毒粒子，而U1细胞产生有缺陷的、无感染性的颗粒。虽然3'-叠氮-3'-脱氧胸苷（AZT）可预防易感细胞的急性HIV感染，但它不能阻止感染细胞系中HIV表达的诱导。相反，α干扰素（IFN-α）在佛波酯刺激这两种细胞系后，抑制逆转录酶和病毒抗原释放到培养上清中。此外，IFN-α抑制完整HIV病毒粒子的产生或释放（或两者），但对细胞相关病毒蛋白的量没有影响。同样，在佛波酯刺激ACH-2细胞后，IFN-α减少分泌到培养上清中的有感染性病毒粒子数量，但对细胞相关病毒的感染性没有影响。这些发现支持联合使用在HIV复制早期（AZT）和晚期（IFN-α）均有作用的抗病毒药物。
