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HIV-1感染在不同T淋巴细胞亚群中的分布:初治患者与经治患者的比较

Distribution of HIV-1 infection in different T lymphocyte subsets: antiretroviral therapy-naïve vs. experienced patients.

作者信息

Perez Raul, Gibson Sonia, Lopez Pablo, Koenig Ellen, De Castro Marisol, Yamamura Yasuhiro

机构信息

Department of Internal Medicine, Wayne State University , Detroit, Michigan, USA.

出版信息

AIDS Res Hum Retroviruses. 2011 Apr;27(4):399-410. doi: 10.1089/aid.2010.0176. Epub 2010 Nov 7.

Abstract

Memory CD4 T cells are the primary targets of HIV-1 infection, which then subsequently spreads to other T lymphocyte subsets. Antiretroviral therapy (ART) alters the pattern of HIV-1 distribution. Blood samples were collected from ART-naïve or -experienced HIV-1 patients, and the memory and naïve subsets of CD4(+) and CD8(+) T lymphocytes, respectively, were isolated by cell sorting. DNA was extracted and the HIV-1 env C2/V3 region PCR amplified. Amplicons were cloned and sequenced, and genetic relatedness among different HIV-1 compartments was determined by the phylogenetic analysis of clonal sequences. The viral V3 sequence of HIV-1 in each compartment was analyzed by using webPSSM to determine CCR5 or CXCR4 coreceptor binding property of the virus. The direction of viral migration among involved compartments was determined by using the MacClade program. In ART-naïve patients, HIV-1 was generally confined to the memory CD4 T (mT4) cell compartment, even though in a few cases, naïve CD4 T (nT4) cells were also infected. When this occurred, the HIV-1 gene migrated from nT4 to mT4. In contrast, HIV-1 was detected in nT4 and mT4 as well as in the memory CD8 T (mT8) compartments of ART-experienced patients. However, no clear pattern of directional HIV-1 gene flow among the compartments could be determined because of the small sample size. All HIV-1-infected T cell compartments housed the virus that used either CCR5 or CXCR4 as the coreceptor.

摘要

记忆性CD4 T细胞是HIV-1感染的主要靶细胞,随后病毒会扩散到其他T淋巴细胞亚群。抗逆转录病毒疗法(ART)会改变HIV-1的分布模式。从未接受过ART治疗或接受过ART治疗的HIV-1患者中采集血样,通过细胞分选分别分离出CD4(+)和CD8(+) T淋巴细胞的记忆亚群和初始亚群。提取DNA并对HIV-1 env C2/V3区域进行PCR扩增。对扩增产物进行克隆和测序,并通过克隆序列的系统发育分析确定不同HIV-1区室之间的遗传相关性。使用webPSSM分析每个区室中HIV-1的病毒V3序列,以确定病毒的CCR5或CXCR4共受体结合特性。使用MacClade程序确定相关区室之间病毒迁移的方向。在未接受过ART治疗的患者中,HIV-1通常局限于记忆性CD4 T(mT4)细胞区室,尽管在少数情况下,初始CD4 T(nT4)细胞也会被感染。当这种情况发生时,HIV-1基因会从nT4迁移到mT4。相比之下,在接受过ART治疗的患者的nT4、mT4以及记忆性CD8 T(mT8)区室中均检测到了HIV-1。然而,由于样本量较小,无法确定区室之间HIV-1基因的明确流动模式。所有感染HIV-1的T细胞区室中都存在以CCR5或CXCR4作为共受体的病毒。

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