Measles virus inhibits human immunodeficiency virus type 1 reverse transcription and replication by blocking cell-cycle progression of CD4+ T lymphocytes.
Acute measles virus (MV) infection results in a decrease in plasma human immunodeficiency virus type 1 (HIV-1) RNA levels in co-infected children. An in vitro peripheral blood mononuclear cell (PBMC) culture system was used to assess the mechanisms by which MV blocks HIV-1 replication. MV inhibited proliferation of CD4(+) T lymphocytes, the target cell for HIV-1 replication. In the presence of MV, cells did not progress to G(1b) and S phases, steps critical for the completion of HIV-1 reverse transcription and productive replication. This block in cell-cycle progression was characterized by an increased proportion of CD4(+) and HIV-1-infected cells retained in the parental generation in PBMCs co-cultured with MV and HIV-1, and decreased levels of cyclins and RNA synthesis. Early HIV-1 replication was also inhibited in the presence of MV, as measured by reduced expression of a luciferase reporter gene and lower levels of both early (LTR) and late (LTR-gag) DNA intermediates of HIV-1 reverse transcription in the presence of CCR5-tropic HIV-1. The effects of MV on lymphoproliferation and p24 antigen production were reproduced by n-butyrate and hydroxyurea, drugs that block the cell cycle in G(1a) and G(1)/S, respectively. It was concluded that MV inhibits HIV-1 productive replication in part by blocking the proliferation of CD4(+) T lymphocytes.
García
Mayra
M
Cellular and Molecular Medicine, School of Medicine; Johns Hopkins University, Baltimore, MD 21205, USA.|W. Harry Feinstone Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA.
Yu
Xiao-Fang
XF
W. Harry Feinstone Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA.
Griffin
Diane E
DE
W. Harry Feinstone Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA.
Moss
William J
WJ
Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA.|W. Harry Feinstone Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA.
D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D049109:Cell Proliferation; D002478:Cells, Cultured; D015536:Down-Regulation; D015967:Gene Expression Regulation, Viral; D015658:HIV Infections / Q000150:complications / Q000821:virology; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007963:Leukocytes, Mononuclear; D008457:Measles / Q000150:complications / Q000821:virology; D008459:Measles virus / Q000502:physiology*; D019713:Receptors, CCR5 / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism; D048348:Reverse Transcription / Q000235:genetics; D014779:Virus Replication
D019713:Receptors, CCR5; D019718:Receptors, CXCR4