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

HIV-1 感染在不同 T 淋巴细胞亚群中的分布:未接受过抗逆转录病毒治疗的患者与接受过抗逆转录病毒治疗的患者

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

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.

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