A CCR5+ memory subset within HIV-1-infected primary resting CD4+ T cells is permissive for replication-competent, latently infected viruses in vitro

HIV-1 感染的原发性静息 CD4+ T 细胞内的 CCR5+ 记忆亚群允许体外具有复制能力的潜伏感染病毒

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作者:Kazutaka Terahara, Ryutaro Iwabuchi, Masahito Hosokawa, Yohei Nishikawa, Haruko Takeyama, Yoshimasa Takahashi, Yasuko Tsunetsugu-Yokota

Objective

Resting CD4+ T cells are major reservoirs of latent HIV-1 infection, and may be formed during the early phase of the infection. Although CCR5-tropic (R5) HIV-1 is highly transmissible during the early phase, newly infected individuals have usually been exposed to a mixture of R5 and CXCR4-tropic (X4) viruses, and X4 viral DNA is also detectable in the host. Our aim was to identify which subsets of resting CD4+ T cells contribute to forming the latent reservoir in the presence of both X4 and R5 viruses.

Results

Primary resting CD4+ naïve T (TN) cells, CCR5- memory T (TM) cells, and CCR5+ TM cells isolated by flow cytometry were infected simultaneously with X4 and R5 HIV-1, which harbored different reporter genes, and were cultured in the resting condition. Flow cytometry at 3 days post-infection demonstrated that X4 HIV-1+ cells were present in all three subsets of cells, whereas R5 HIV-1+ cells were present preferentially in CCR5+ TM cells, but not in TN cells. Following CD3/CD28-mediated activation at 3 days post-infection, numbers of R5 HIV-1+ cells and X4 HIV-1+ cells increased significantly only in the CCR5+ TM subset, suggesting that it provides a major reservoir of replication-competent, latently infected viruses.

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