摘要
Chemokine receptors, mainly CCR5 and CXCR4, have been proved to be the important coreceptors in HIV 1 entry. HIV 1 disease progression is, in general, characterized by an initial predominance of CCR5 using macrophage tropic, non syncytium inducing (NSI) isolates, switching later to CXCR4 using T cell tropic, syncytium inducing (SI) isolates. How this shift occurs and how the shift can be controlled are still unclear. Since patients with rapid decline of T cell counts have constantly high levels of IFN γ in the sera and lymphoid nodes, we investigated the influence of this cytokine on the expression of the HIV 1 coreceptors CCR5 and CXCR4 on the cell surfaces of human monocytic cell line U937 and promonocyte NB4. IFN γ could intensively enhance the expression of both, while a low level of CCR5 expression was detected in two cell lines before stimulation. The results of semiquantitative RT PCR also confirm the up regulation. As the newly generated X4 strains have been demonstrated to be insensitive to chemokine in some reports, IFN γ may play an important role in selecting CXCR4 used strains.
Chemokine receptors, mainly CCR5 and CXCR4, have been proved to be the important coreceptors in HIV 1 entry. HIV 1 disease progression is, in general, characterized by an initial predominance of CCR5 using macrophage tropic, non syncytium inducing (NSI) isolates, switching later to CXCR4 using T cell tropic, syncytium inducing (SI) isolates. How this shift occurs and how the shift can be controlled are still unclear. Since patients with rapid decline of T cell counts have constantly high levels of IFN γ in the sera and lymphoid nodes, we investigated the influence of this cytokine on the expression of the HIV 1 coreceptors CCR5 and CXCR4 on the cell surfaces of human monocytic cell line U937 and promonocyte NB4. IFN γ could intensively enhance the expression of both, while a low level of CCR5 expression was detected in two cell lines before stimulation. The results of semiquantitative RT PCR also confirm the up regulation. As the newly generated X4 strains have been demonstrated to be insensitive to chemokine in some reports, IFN γ may play an important role in selecting CXCR4 used strains.
基金
Supported by the National Key Basic Research Specific Funds (No. G19990 75 6 0 7) and the National ScienceFoundation for Outstanding Young Scientist of China(No. 30 0 2 5 0 38)
