Interference between human herpesvirus 7 and HIV-1 in mononuclear phagocytes.
Human herpesvirus 7 (HHV-7) uses CD4 as a cellular membrane receptor and thereby interferes with infection of CD4+ T cells by HIV-1. We studied the interactions between HHV-7 and a macrophage-tropic HIV-1 isolate (HIV-1BaL) 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 signs of virus replication or cytopathic effects. Nevertheless, when macrophages were pre-exposed to either live or UV-inactivated HHV-7 and subsequently infected with HIV-1BaL, a significant dose-dependent inhibition 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 synthesis of HIV-1 proviral DNA in macrophages pretreated with HHV-7 was completely inhibited during the early stages after infection, suggesting that HHV-7 blocks HIV-1 at the level of interaction with the CD4 receptor. Consistent with this concept, both macrophage and CD4+ T cell cultures with pre-established HIV-1 infection were not susceptible to inhibitory effects of HHV-7. The proliferative response of PBMC to mitogens was only marginally inhibited by exposure to HHV-7 before mitogen stimulation, indicating that the inhibition of HIV-1 infection was not due to a negative effect on cell proliferation. These data demonstrate that HHV-7 is a powerful inhibitor of HIV-1 infection in cells of the mononuclear phagocytic lineage, despite its inability to replicate actively in such cells.
Crowley
R W
RW
Laboratory of Tumor Cell Biology, National Cancer Institute, Bethesda, MD 20894, USA.
Secchiero
P
P
Zella
D
D
Cara
A
A
Gallo
R C
RC
Lusso
P
P
D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D004279:DNA, Viral / Q000096:biosynthesis; D015497:HIV-1 / Q000276:immunology*; D016199:Herpesvirus 7, Human / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology / Q000821:virology*; D009000:Monocytes / Q000276:immunology / Q000821:virology*; D011533:Proviruses / Q000235:genetics / Q000276:immunology; D014762:Viral Interference / Q000276:immunology*
D004279:DNA, Viral