Productive HIV-1 infection is enriched in CD4-CD8- double negative (DN) T cells at pleural sites of dual infection with HIV and Mycobacterium tuberculosis

• Published in: Archives of virology Vol. 161; no. 1; pp. 181 - 187
• Main Authors: Meng, Qinglai, Canaday, David H, McDonald, David J, Mayanja-Kizza, Harriet, Baseke, Joy, Toossi, Zahra
• Format: Journal Article
• Language: English
• Published: Vienna Springer Vienna 2016
• Subjects: Adult; Biomedical and Life Sciences; Biomedicine; Brief Report; CD4-positive T-lymphocytes; CD8-positive T-lymphocytes; Coinfection - immunology; Coinfection - microbiology; Coinfection - virology; Female; HIV infections; HIV Infections - immunology; HIV Infections - microbiology; HIV Infections - virology; HIV-1 - physiology; HLA antigens; Human immunodeficiency virus 1; Humans; Infectious Diseases; Male; Medical Microbiology; mixed infection; mutants; Mycobacterium tuberculosis; Mycobacterium tuberculosis - physiology; Pleura - immunology; T-Lymphocytes - immunology; Tuberculosis - immunology; Tuberculosis - microbiology; viral load; Virology; viruses; Young Adult; HIV-1; PFMC; Tuberculosis; Double-negative T cell; T cell
• ISSN: 0304-8608; 1432-8798; 1432-8798
• DOI: 10.1007/s00705-015-2640-7

A higher human immunodeficiency virus 1 (HIV-1) viral load at pleural sites infected with Mycobacterium tuberculosis (MTB) than in peripheral blood has been documented. However, the cellular source of productive HIV infection in HIV-1/MTB-coinfected pleural fluid mononuclear cells (PFMCs) remains unclear. In this study, we observed significant quantities of HIV-1 p24⁺ lymphocytes in PFMCs, but not in peripheral blood mononuclear cells (PBMCs). HIV-1 p24⁺ lymphocytes were mostly enriched in DN T cells. Intracellular CD4 expression was detectable in HIV-1 p24⁺ DN T cells. HIV-1 p24⁺ DN T cells showed lower surface expression of human leukocyte antigen (HLA)-ABC and tetherin than did HIV-1 p24⁺ CD4 T cells. Upon in vitro infection of PFMC CD4 T cells from TB mono-infected subjects, Nef- and/or Vpu-deleted HIV mutants showed lower generation of HIV-1 p24⁺ DN T cells than the wild-type virus. These data indicate that productively HIV-1-infected DN T cells, generated through down-modulation of surface CD4, likely by HIV-1 Nef and Vpu, are the predominant source of HIV-1 at pleural sites of HIV/MTB coinfection.