Kannagi M, Masuda T, Hattori T, Kanoh T, Nasu K, Yamamoto N, Harada S
Department of Biodefence and Medical Virology, Kumamoto University Medical School, Japan.
J Virol. 1990 Jul;64(7):3399-406. doi: 10.1128/JVI.64.7.3399-3406.1990.
A long asymptomatic period is one of the characteristics of human immunodeficiency virus (HIV) infection, despite its fatal consequences. Antiviral defense in HIV-infected individuals controls viral replication during this period. In the present study, we demonstrate that peripheral blood leukocytes (PBL) of asymptomatic HIV-1 carriers, following exogenous HIV-1 infection in vitro, do not support viral replication. These cells do not produce detectable amounts of reverse transcriptase or accumulate unintegrated proviral DNA. This is a striking contrast to the behavior of HIV-1-infected PBL of seronegative individuals, which produce large amounts of RT and unintegrated DNA. Such resistance to HIV-1 replication is not seen in PBL of patients with advanced disease. Since the binding of HIV-1 to CD4 molecule is not impaired in PBL of asymptomatic carriers, the interference with HIV replication must occur after the stage of virus binding. PBL lose their resistance when CD8+ lymphocytes are removed. In addition, these PBL are not resistant to an exogenous infection with HIV-2. These observations suggest that certain populations of CD8+ lymphocytes of asymptomatic HIV-1 carriers operate on the target cells in PBL to block viral replication in an HIV-1-specific manner. Such CD8+ lymphocyte-mediated interference with HIV replication could play an important role in the maintenance of the period of disease latency.
尽管人类免疫缺陷病毒(HIV)感染会带来致命后果,但其特征之一是存在较长的无症状期。在此期间,HIV感染个体的抗病毒防御机制可控制病毒复制。在本研究中,我们证明,体外感染外源性HIV-1后,无症状HIV-1携带者的外周血白细胞(PBL)不支持病毒复制。这些细胞不会产生可检测量的逆转录酶,也不会积累未整合的前病毒DNA。这与血清阴性个体的HIV-1感染PBL的行为形成了鲜明对比,后者会产生大量的逆转录酶和未整合的DNA。晚期疾病患者的PBL中未观察到这种对HIV-1复制的抗性。由于无症状携带者的PBL中HIV-1与CD4分子的结合未受损,因此对HIV复制的干扰必定发生在病毒结合阶段之后。去除CD8 +淋巴细胞后,PBL会失去其抗性。此外,这些PBL对外源性HIV-2感染没有抗性。这些观察结果表明,无症状HIV-1携带者的某些CD8 +淋巴细胞群体作用于PBL中的靶细胞,以HIV-1特异性方式阻断病毒复制。这种CD8 +淋巴细胞介导的对HIV复制的干扰可能在维持疾病潜伏期方面发挥重要作用。