Subversion of chemokine receptors by HIV: how can we exploit this?

Abstract

The recent discovery that the chemokines RANTES (regulated upon activation, normal T-cell-expressed and secreted), macrophage inflammatory protein-1alpha (MIP-1a), and macrophage inflammatory protein-1beta (MIP-1b) are important modulators of HIV-1 infection and the subsequent identification of the essential role that chemokine receptors play as co-receptors for HIV-1 infection have provided new insight into the pathogenesis of HIV-1. On May 10, 1996, Ed Berger's group of the NIH announced the identity of one of the elusive ;co-receptors' for HIV-1. This, and subsequent papers showing that the expression of specific seven transmembrane (7TM) chemokine receptors and CD4 confers susceptibility to infection by HIV-1, has led to rapid and exciting advances in both chemokine and HIV research. During the year since then, a number of elegant studies by different groups have identified additional co-receptors for HIV-1 and the receptor involved in HIV-2 infection, as well as extended our understanding of the mechanism HIV utilises to enter cells. A number of researchers at academic institutes, pharmaceutical and biotech companies are gambling that this will translate into new therapeutics for the treatment of HIV infection and AIDS.

Biochemical and Biologic Characterization of Exosomes and Microvesicles as Facilitators of HIV-1 Infection in Macrophages

“…The intensity of cytokine response from the target cells is unique to each vesicle population. Interestingly, these pro-inflammatory cytokines have also been shown to influence the viral life cycle and enhance HIV-1 infection (23, 24). …”

Exosomes in HIV infection

“…In this case, a large number of DC/T lymphocyte clusters are induced, and ultimately leads to higher levels of HIV metastasis to T lymphocytes [ 60 ]. Exosomes also carry some cytokines, such as interleukin (IL)-3, IL-4, IL-8, and IL-17 [ 61 ], which affect the virus's life cycle and enhance HIV infection [ 62 , 63 ]. Some studies demonstrated that exosomes promote HIV infection by affecting HIV-derived proteins.…”

“…Exosomes also carry some cytokines, such as interleukin (IL)-3, IL-4, IL-8, and IL-17 [61], which affect the virus's life cycle and enhance HIV infection [62,63]. Some studies demonstrated that exosomes promote HIV infection by affecting HIVderived proteins.…”