Endothelium plays an important role in the pathogenesis of viral infections, and a potential involvement in HIV infection is suggested by several in vivo observations. In vitro studies gave conflicting results regarding the susceptibility of endothelial cells (EC) to HIV, depending on the tissue source of EC and on their functional status. In fact, microvascular EC from adipose tissue, renal glomeruli, brain capillaries, and epathic sinusoids can be productively infected by HIV-1, via CD4-dependent or -independent pathways. Macrovascular EC are generally found to be resistant to HIV-1 infection, unless treated with a combination of pro-inflammatory cytokines, or in a status of active proliferation. Quiescent or low-replicating human umbilical vein endothelial cells (HUVEC) can be abortively infected with HIV-1, but virus production is rescued by cocultivation with either lymphoblastoid or activated T-cells from adult or cord blood, giving rise to substantial virus yields in coculture supernatants. The interaction of HIV-1 with HUVEC is mediated by the alternate receptor GalCer, but is enhanced by the presence of antibodies to membrane structures present on both HUVEC and HIV-1, such as ICAM-1, acting as a molecular bridge. Treatment of HUVEC with IFN-γ causes a dose-dependent enhancement of HIV-1 yield in cocultures. This effect does not appear to be mediated by early replicative events occurring in HUVEC, such as HIV-1 adsorption or retrotranscription. Rather, IFN-γ-mediated enhancement of ICAM-1 exposed on the surface of HUVEC increases adhesion of T-cells to infected HUVEC, leading to increased viral transmission. The pathological significance of low-productive or abortive infection of HUVEC with HIV-1 is potentially important, since EC expressing little, if any, virus antigen, can escape the elimination by cytotoxic cells, still retaining the capability to transmit the infection to T-cells, through a mechanism that is enhanced during the inflammatory process. These considerations, together with the fact that the inflammatory process is often accompanied by conditions favoring EC proliferation, such as vessel repair, and by the presence of HIV-stimulatory cytokines, and the fact that these conditions can determine the switch from abortive to productive HIV-1 infection, support the relevance of EC involvement in the pathogenesis of HIV-1 infection and progression, especially in view of the critical role of EC in establishing the selective properties of most anatomical barriers.
|Number of pages||12|
|Journal||Perspectives in Drug Discovery and Design|
|Publication status||Published - 1996|
ASJC Scopus subject areas
- Organic Chemistry
- Drug Discovery