Measles virus inhibits human immunodeficiency virus type 1 reverse transcription and replication by blocking cell-cycle progression of CD4+ T lymphocytes

Abstract

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.

HIV-1 Infection Ex Vivo Accelerates Measles Virus Infection by Upregulating Signaling Lymphocytic Activation Molecule (SLAM) in CD4 + T Cells

“…In addition, both strains of MV inhibited HIV-1 replication (Fig. 1C), which is consistent with previous reports (7,8,10). Although the precise mechanism(s) underlying HIV-1 suppression by MV is not completely understood, the reduction of p24 antigen observed in the culture supernatant occurred in parallel with the elimination of HIV-1-infected cells after MV infection.…”

“…1C). These results are consistent with those reported previously; i.e., MV infection inhibits the replication of HIV-1 (7,8,10).…”

“…Garcia et al studied HIV-1 replication in peripheral blood mononuclear cells (PBMCs) coinfected with MV and found that MV-induced inhibition of lymphocyte proliferation suppresses HIV-1 replication, but without any apparent increase in the production of chemokines or any other soluble factors in coinfected cultures (7). In a more recent study, the same group demonstrated that the cell cycle progression of T cells, which is required for efficient HIV-1 replication, was blocked by MV (8); however, it is still not clear whether HIV-1 affects MV infection directly or indirectly.…”

Long-term safety and serologic response to measles, mumps, and rubella vaccination in HIV-1 infected adults

“…[36–39] From our study, it appears that MMR vaccination does not significantly impact VL, although we were limited by low numbers of subjects not receiving HAART, by unavailable VL data during the follow-up period, and by long follow-up intervals that may have missed short-term effects of vaccination. This is, however, in agreement with other studies reporting a similar lack of VL change after measles-rubella vaccination in 11 Ugandan children[40] and continued viral suppression in HAART-treated adults after MMR vaccination.…”

The potential impact of coinfection on antimicrobial chemotherapy and drug resistance

“…The net result is the same – the focal pathogen may have a lower replication rate as a result of the immune-modulatory activity of the first (e.g., measles–HIV coinfection [56]). This would reduce the potential for the spread of resistance in the focal pathogen.…”