INTERFERON-ALPHA BUT NOT AZT SUPPRESSES HIV EXPRESSION IN CHRONICALLY INFECTED CELL-LINES
INTERFERON-ALPHA BUT NOT AZT SUPPRESSES HIV EXPRESSION IN CHRONICALLY INFECTED CELL-LINES
复制标题
DOI：
10.1126/science.2470148
复制
发表时间：
1989-05-05
期刊：
影响因子：
56.9
通讯作者：
FAUCI, AS
中科院分区：
文献类型：
--
作者：
POLI, G;ORENSTEIN, JM;FAUCI, AS
慢性感染人类免疫缺陷病毒1型（HIV-1）的前单核细胞（U1）和T淋巴细胞（ACH-2）细胞系组成型表达低水平的病毒，但表达可以诱导佛波醇酯和细胞因子。ACH-2细胞产生感染性病毒粒子，而U1细胞产生有缺陷的非感染性粒子。虽然3“-叠氮基-3”-脱氧胸苷（AZT）阻止了易感细胞的急性HIV感染，但它不能阻止感染细胞系中HIV表达的诱导。相反，干扰素α（IFN-α）在佛波酯刺激两种细胞系后，抑制逆转录酶和病毒抗原释放到培养上清液中。此外，IFN-α.抑制整个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。此外，在ACH-2细胞的佛波醇酯刺激后，IFN-α减少分泌到培养上清液中的感染性病毒颗粒的数量，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早期（AZT）和晚期（IFN-α）都有作用的抗病毒剂。艾滋病毒复制阶段。
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''-deoxythmidine (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 reelease 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.) stage of HIV replication.