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Journals The FASEB Journal Volume 21 Issue 14

ABSTRACT Key Words: HIV-1 coreceptors signal transducers infection CCR5 is a chemoattractant receptor for several chemokines (MIP-1 , MIP-1 , and RANTES) that plays an important role in the early phases of infection by the human immunodeficiency virus 1 (HIV-1). CCR5 is a leukocyte coreceptor of HIV-1 (1) that interacts with the viral envelope glycoprotein gp120 after the latter binds to CD4, the main HIV-1 receptor. Only HIV-1 isolates that bind to CCR5 were shown to infect macro4038 phages, which are major reservoirs of the virus (2). Structural protein rearrangements allow the viral transmembrane subunit gp41 to fuse the viral envelope with the membrane of target cells, thereby facilitating HIV-1 uptake. The provirus genome is subjected to reverse transcription (3, 4) and integration into the host genome, and can establish a latent infection (5, 6). HIV-1 replication is dependent on activation of a single promoter present in the long terminal repeat (LTR) region of HIV-1 genome that contains binding sites for the HIV-1 transactivator protein Tat (7, 8) and for various endogenous transcription factors (9, 10). Viral replication requires a state of activation of host cells since HIV-1 does not infect resting CD4 T cells from peripheral blood

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CCR5 signaling through phospholipase D involves p44/42 MAP-kinases and promotes HIV-1 LTR-directed gene expression

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