11th International AIDS Conference Vancouver, British Columbia — July 7-12, 1996

Int Conf AIDS 1996 Jul 7-12; 11:217 (abstract no. Th.A.390)
Capobianchi MR, BarresiC, Gessani S, Borghi P, Fantuzzi L, Ameglio F, Belardelli F, Dianzani F; Institute of Virology, University "La Sapienza", Rome, Italy. Fax: 39.6.4469024. E-mail: Virosap@flashnet.it.

OBJECTIVE: To explore the possibility that HIV could stimulate human cytomegalovirus (HCMV) infection in monocytes by indirect mechanisms.

METHODS: Freshly isolated normal monocytes were exposed to recombinant HIV-1 structural proteins, then infected with HCMV. The extent of HCMV infection was evaluated by both immediate early antigen (IEA) expression and infectious virus yield. sCD4 and multibranched V3 loop peptides were used to establish the gp120 membrane interaction with monocytes reponsible for HCMV upmodulation. IL-8 gene expression by stimulated monocytes was evaluated by both RT-PCR and shed protein detected by ELISA. Mab to IL-8 were used to establish to role of this cytokine in the HCMV stimulation.

RESULTS: Recombinant gp120, but not other HIV-1 structural proteins, dose-dependently stimulate IEA expression in freshly isolated normal monocytes infected with HCMV. The gp120-driven HCMV stimulation is also detected at the level of infectious virus yield. V3 loop multibranched peptides, but not sCD4, abrogate the gp120 stimulation of IEA expression by monocytes, suggesting that the effect is specific for gp120, and is likely not mediated by CD4 interaction. HCMV stimulation is also observed when conditioned medium from gp120-stimulated cultures is added to naive monocytes, suggesting that the effect is mediated by gp120-induced soluble factors. Interleukin (IL)-8 gene expression is enhanced in monocytes treated with gp120 at the level of both mRNA and released protein. A monoclonal antibody capable to neutralize IL-8 activity abrogates the gp120-induced HCMV stimulation in monocyte cultures. Diploid fibroblasts, that have been shown to respond to exogenous IL-8 activation, but do not respond to gp120 administration in terms of IL-8 release, are also insensitive to the gp120-induced HCMV stimulation.

CONCLUSIONS: These data indicate that HIV-1 gp120 induces a stimulation of productive infection with HCMV in monocytes, and that such stimulation could be mediated by the upregulation of IL-8 gene expression. This is the first evidence that HIV-1 could affect HCMV replication indirectly, by enhancing the IL-8 production, via the interaction of gp120 with the monocyte membrane, in the complete absence of retroviral replication. Since in HIV-1 infected individuals HCMV infection is frequently activated, and the levels of circulating IL-8 are enhanced, our results may have pathogenetic implications. Clinical relevance of these findings is presently under evaluation.

960707
ThA390

Copyright © 1996 - International AIDS Society (IAS). Reproduction of this abstract (other than one copy for personal reference) must be cleared through the IAS.