DUAL EFFECT OF INTERLEUKIN-4 ON HIV-1 EXPRESSION - IMPLICATIONS FOR VIRAL PHENOTYPIC SWITCH AND DISEASE PROGRESSION

We report that interleukin 4 (IL-4) inhibits the propagation of non-sy ncytia-inducing and increases the propagation of syncytia-inducing HIV -1 isolates by two mechanisms. It differentially regulates the two maj or HIV-I coreceptors, CCR5 and CXCR4, in human peripheral blood mononu clear cells, increasing CXCR4 and decreasing CCR5 expression in primar y CD4(+) T-lymphocytes, In addition, IL-4 stimulates the expression of all HIV-1 isolates via a transcriptional activation mechanism. The co mbination of these effects results in increased propagation of CXCR4-u sing and inhibition of CCR5-using HIV-1 strains, IL-4 also activates H IV-1 expression in primary monocytes/macrophages but does not affect C CRS expression. These results identify IL-4 as an important regulator of HIV-1 and suggest a critical role for this cytokine in the control of viral evolution and in the phenotypic switch from non-syncytia-indu cing to syncytia-inducing, which leads to accelerated disease progress ion.