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

• Published in: BMC research notes Vol. 12; no. 1; pp. 242 - 7
• Main Authors: Terahara, Kazutaka, Iwabuchi, Ryutaro, Hosokawa, Masahito, Nishikawa, Yohei, Takeyama, Haruko, Takahashi, Yoshimasa, Tsunetsugu-Yokota, Yasuko
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 29.04.2019; BioMed Central; BMC
• Subjects: Adult; Analysis; CCR5 protein; CD28 antigen; CD3 antigen; CD4 antigen; CD4 lymphocytes; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - virology; CXCR4 protein; Dendritic cells; Development and progression; Diagnosis; DNA; DNA viruses; DNA, Viral - genetics; DNA, Viral - metabolism; Drug therapy; Experiments; Flow cytometry; Gene Expression; Genes; Healthy Volunteers; HIV; HIV infections; HIV-1 - pathogenicity; HIV-1 - physiology; Host-Pathogen Interactions - genetics; Host-Pathogen Interactions - immunology; Human immunodeficiency virus; Humans; Immunologic Memory; Infection; Infections; Latent infection; Latent reservoir; Lymphocytes; Lymphocytes T; Memory cells; Physiological aspects; Primary Cell Culture; Receptors, CCR5 - genetics; Receptors, CCR5 - immunology; Receptors, CXCR4 - genetics; Receptors, CXCR4 - immunology; Replication; Research Note; Resting CD4+ T cells; T cells; Testing; Viral Tropism; Virus Latency; Virus Replication; Viruses; Japan; United States > US; Resting CD4+ T cells; HIV; Latent reservoir
• ISSN: 1756-0500; 1756-0500
• DOI: 10.1186/s13104-019-4281-5

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. Primary resting CD4 naïve T (T ) cells, CCR5 memory T (T ) cells, and CCR5 T 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 cells, but not in T 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 subset, suggesting that it provides a major reservoir of replication-competent, latently infected viruses.