Human immunodeficiency virus type 1 gp120 stimulates cytomegalovirus replication in monocytes: possible role of endogenous interleukin-8

Abstract

Recombinant gp120, but not other human immunodeficiency type 1 (HIV-1) structural proteins, dose-dependently stimulates human cytomegalovirus (HCMV) immediate-early antigen (IEA) expression and infectious virus yield in freshly isolated normal monocytes infected with HCMV. Monoclonal antibodies (MAbs) recognizing the gp120 V3 loop, as well as V3 loop octameric multibranched peptides and antibody to galactocerebroside, but not sCD4, abrogate the gp120 stimulation of IEA expression, suggesting that the effect involves V3 loop-galactocerebroside interaction and is not mediated by CD4. Interleukin 8 (IL-8) gene expression is enhanced in monocytes treated with gp120 at the level of both mRNA and released protein. Exogenous IL-8 could replace gp120 in the stimulation of HCMV infection, while a MAb capable of neutralizing IL-8 activity abrogates the gp120-induced HCMV stimulation. These data indicate that HIV-1 glycoprotein induces stimulation of productive infection of monocytes with HCMV and that such stimulation may be mediated by the upregulation of IL-8 gene expression. This is the first evidence that HIV-1 may affect HCMV replication indirectly, via the interaction of gp120 with the monocyte membrane, in the complete absence of retroviral replication, through the stimulation of IL-8 release. Because in HIV-1-infected individuals, HCMV infection is frequently activated and the levels of circulating IL-8 are enhanced, these findings may be pathogenetically relevant.