Active HIV-1 redistribution and replication in the brain with HIV encephalitis

Active HIV-1 redistribution and replication in the brain with HIV encephalitis
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DOI:
10.1007/s007050050483
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发表时间:
1999-01-01
影响因子:
2.7
通讯作者:
Iwamoto, A
Iwamoto, A
中科院分区:
医学4区
文献类型:
--
作者:
Gatanaga, H;Oka, S;Iwamoto, A

文献摘要

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中枢神经系统 (CNS) 在人类免疫缺陷病毒 1 型 (HIV-1) 感染中尤为重要。首先,中枢神经系统可能难以进行抗逆转录病毒治疗,并可能成为残留病毒的避难所。其次,HIV-1 感染可能导致艾滋病痴呆症 (ADC),最终导致 HIV-1 脑炎。为了检查耐药性模式以及脑炎在增强病毒重新分布到 CNS 中的作用,我们比较了两名接受齐多夫定 (AZT) 治疗的 HIV-1 脑炎患者和两名未感染 HIV-1 脑炎患者的脾脏和大脑的 pol 基因准种。尽管在所有患者的脾脏和大脑中都发现了不同程度的AZT耐药性,但系统发育分析表明,在未患HIV-1脑炎的患者的体循环(脾脏)和中枢神经系统(大脑)中准种的发育相当独立,而在患有HIV-1脑炎的患者的两个区室中获得了相似的pol基因序列。 HIV-1脑炎患者的env基因V3区在脾脏和大脑中表现出明显的准种。我们的结果表明,在脑炎病例中,HIV-1 重新分布到中枢神经系统更加活跃,并且晚期分布到中枢神经系统的 HIV-1 在 env 基因 V3 区域施加一定的选择压力下生长活跃。
The central nervous system (CNS) is of particular importance in human immunodeficiency virus type 1 (HIV-1) infection. First, the CNS may be difficult to access for anti-retroviral treatment and may become a sanctuary for residual viruses. Second, HIV-1 infection may lead to AIDS dementia complex (ADC) culminating in HIV-1 encephalitis. In order to examine the pattern of drug resistance and the role of encephalitis in enhancing viral redistribution to the CNS, we compared pol gene quasispecies of the spleen and brain in two patients with and two patients without HIV-1 encephalitis, who had been treated with zidovudine (AZT). Although a variable degree of AZT resistance was noted in both the spleen and brain of all patients, phylogenetic analysis indicated that quasispecies developed rather independently in the systemic circulation (spleen) and CNS (brain) of patients without HIV-1 encephalitis, while similar pol gene sequences were obtained from the two compartments of patients with HIV-1 encephalitis. env gene V3 region of patients with HIV-1 encephalitis showed distinct quasispecies in the spleen and brain. Our results suggest that HIV-1 redistribution to CNS is more active in cases with encephalitis and that HIV-1 distributed late to CNS grow actively under certain selective pressure exerted on the V3 region of the env gene.