Abstract

Binding of HIV gp120 to the chemokine coreceptor CXCR4 mediates signal transduction that promotes actin dynamics critical for the establishment of viral latency in resting CD4 T cells. To some extent, this gp120-mediated signal transduction resembles the chemotactic response mediated by chemokines such as the stromal cell-derived factor-1 alpha (SDF-1). It has been suggested that gp120 functions as a bona fide chemokine to attract or repel blood CD4 T cells. To determine whether gp120 is a viral chemoattractant, we compared the chemotactic properties of gp120 with those of SDF- 1, and confirmed previous observations that gp120 possesses some chemotactic ability at certain dosages. However, when we examined gp120 in a range of dosages, we found that in general, gp120 only attracts or repels blood resting CD4 T cells at a low level, and there is no clear pattern of dosage-dependency as normally seen in a typical chemokine. These irregularities of gp120 were observed in multiple donors. Nevertheless, gp120 aberrantly interferes with SDF-1-mediated T cell chemotaxis and cell migration. These results suggest that gp120 does not act like a typical chemoattractant, although it triggers actin dynamics to facilitate HIV infection.

Keywords: HIV-1, CD4, gp120, CXCR4, SDF-1, chemotaxis, actin, signal transduction, chemoattractant, blood resting