INTERFERENCE BETWEEN HUMAN HERPESVIRUS-7 AND HIV-1 IN MONONUCLEAR PHAGOCYTES

Human herpesvirus 7 (HHV-7) uses CD4 as a cellular membrane receptor a nd thereby interferes with infection of CD4(+) T cells by HIV-1, We st udied the interactions between HHV-7 and a macrophage-tropic HIV-1 iso late (HIV-1(BAL)) in terminally differentiated human peripheral blood monocyte-derived macrophages, another critical target for infection by HIV-1 in vivo, Exposure of macrophages to HHV-7 alone yielded no sign s of virus replication or cytopathic effects, Nevertheless, when macro phages were pre-exposed to either live or UV-inactivated HHV-7 and Sub sequently infected with HIV-1(BAL), a significant dose-dependent inhib ition of HIV-1 replication was documented, At day 7 postinfection, the average level of HIV-1 p24 Ag in cultures from five different donors was reduced by 91.7 +/- 8.3% by pretreatment with live HHV-7 and by 91 .8 +/- 8.2% by pretreatment with UV-inactivated HHV-7, Moreover, the s ynthesis of HIV-1 proviral DNA in macrophages pretreated with HHV-7 wa s completely inhibited during the early stages after infection, sugges ting that HHV-7 blocks HIV-1 at the level of interaction with the CD4 receptor, Consistent with this concept, both macrophage and CD4+ T cel l cultures with pre-established HIV-1 infection were not susceptible t o inhibitory effects of HHV-7. The proliferative response of PBMC to m itogens was only marginally inhibited by exposure to HHV-7 before mito gen stimulation, indicating that the inhibition of HIV-1 infection was not due to a negative effect on cell proliferation, These data demons trate that HHV-7 is a powerful inhibitor of HIV-1 infection in cells o f the mononuclear phagocytic lineage, despite its inability to replica te actively in such cells.