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

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

研究成果: Article

抄録

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 (T N ) cells, CCR5 - memory T (T M ) cells, and CCR5 + T M 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 + T M cells, but not in T N 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 + T M subset, suggesting that it provides a major reservoir of replication-competent, latently infected viruses.

元の言語English
記事番号242
ジャーナルBMC Research Notes
12
発行部数1
DOI
出版物ステータスPublished - 2019 4 29

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T-cells
Viruses
HIV-1
Tropics
Flow cytometry
T-Lymphocytes
Data storage equipment
Viral DNA
Genes
Chemical activation
Flow Cytometry
Infection
In Vitro Techniques
Reporter Genes
HIV Infections

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

これを引用

A CCR5 + memory subset within HIV-1-infected primary resting CD4 + T cells is permissive for replication-competent, latently infected viruses in vitro . / Terahara, Kazutaka; Iwabuchi, Ryutaro; Hosokawa, Masahito; Nishikawa, Yohei; Takeyama, Haruko; Takahashi, Yoshimasa; Tsunetsugu-Yokota, Yasuko.

:: BMC Research Notes, 巻 12, 番号 1, 242, 29.04.2019.

研究成果: Article

Terahara, Kazutaka ; Iwabuchi, Ryutaro ; Hosokawa, Masahito ; Nishikawa, Yohei ; Takeyama, Haruko ; Takahashi, Yoshimasa ; Tsunetsugu-Yokota, Yasuko. / A CCR5 + memory subset within HIV-1-infected primary resting CD4 + T cells is permissive for replication-competent, latently infected viruses in vitro :: BMC Research Notes. 2019 ; 巻 12, 番号 1.
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abstract = "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 + na{\"i}ve T (T N ) cells, CCR5 - memory T (T M ) cells, and CCR5 + T M 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 + T M cells, but not in T N 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 + T M subset, suggesting that it provides a major reservoir of replication-competent, latently infected viruses.",
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AU - Iwabuchi, Ryutaro

AU - Hosokawa, Masahito

AU - Nishikawa, Yohei

AU - Takeyama, Haruko

AU - Takahashi, Yoshimasa

AU - Tsunetsugu-Yokota, Yasuko

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N2 - 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 (T N ) cells, CCR5 - memory T (T M ) cells, and CCR5 + T M 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 + T M cells, but not in T N 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 + T M subset, suggesting that it provides a major reservoir of replication-competent, latently infected viruses.

AB - 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 (T N ) cells, CCR5 - memory T (T M ) cells, and CCR5 + T M 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 + T M cells, but not in T N 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 + T M subset, suggesting that it provides a major reservoir of replication-competent, latently infected viruses.

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KW - Latent reservoir

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