Inhibition of HIV-1 replication in human lymphoid tissues ex vivo by measles virus.
Human immunodeficiency virus (HIV) type 1 replication and disease progression are enhanced by various pathogens in coinfected individuals. However, acute infection with measles virus (MV) has been found to suppress HIV-1 replication in coinfected children. We investigated the mechanisms of this phenomenon using human lymphoid tissues coinfected ex vivo with HIV-1 and MV. MV inhibited both CXCR4-tropic (X4) and CCR5-tropic (R5) HIV-1, but the inhibitory effect was particularly profound for R5 virus, which transmits infection and dominates the early stages of HIV-1 disease. MV inhibits the replication of R5 HIV-1 in coinfected tissues by up-regulation of the CC chemokine RANTES, a well-known inhibitor of R5 HIV-1 infection, and this up-regulation is augmented in tissues coinfected with R5 HIV-1. Deciphering the molecular mechanisms by which MV and other pathogens alter local cytokine/chemokine networks and cause tissue microenvironments to become detrimental to HIV-1 may significantly contribute to the development of effective anti-HIV therapies.
Grivel
Jean-Charles
JC
Laboratory of Molecular and Cellular Biophysics, National Institute of Child Health and Human Development, Bethesda, Maryland 21205, USA.
García
Mayra
M
Moss
William J
WJ
Margolis
Leonid B
LB
D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000378:metabolism; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000378:metabolism; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism; D008459:Measles virus / Q000502:physiology*; D014066:Palatine Tonsil / Q000821:virology*; D046509:Tissue Culture Techniques; D015854:Up-Regulation; D014779:Virus Replication / Q000502:physiology*
C515255:CXCL12 protein, human; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D019402:Macrophage Inflammatory Proteins