Human herpesvirus 8 enhances human immunodeficiency virus replication in acutely infected cells and induces reactivation in latently infected cells.
Human herpesvirus 8 (HHV-8) is etiologically associated with Kaposi sarcoma (KS), the most common AIDS-associated malignancy. Previous results indicate that the HHV-8 viral transactivator ORF50 interacts synergistically with Tat protein in the transactivation of human immunodeficiency virus (HIV) long terminal repeat (LTR), leading to increased cell susceptibility to HIV infection. Here, we analyze the effect of HHV-8 infection on HIV replication in monocyte-macrophage and endothelial cells, as potential targets of coinfection. Primary or transformed monocytic and endothelial cells were infected with a cell-free HHV-8 inoculum and subsequently infected with lymphotropic or monocytotropic strains of HIV. The results show that HHV-8 coinfection markedly increases HIV replication in both cell types. HHV-8 infection induces also HIV reactivation in chronically infected cell lines and in peripheral blood mononuclear cells (PBMCs) from patients with asymptomatic HIV, suggesting the possibility that similar interactions might take place also in vivo. Furthermore, coinfection is not an essential condition, since contiguity of differently infected cells is sufficient for HIV reactivation. The results suggest that HHV-8 might be a cofactor for HIV progression and that HHV-8-infected endothelial cells might play a relevant role in transendothelial HIV spread.
Caselli
Elisabetta
E
Department of Experimental and Diagnostic Medicine, Section of Microbiology, University of Ferrara, Via Borsari 46, 44100 Ferrara, Italy.
Galvan
Monica
M
Cassai
Enzo
E
Caruso
Arnaldo
A
Sighinolfi
Laura
L
Di Luca
Dario
D
D000208:Acute Disease; D002478:Cells, Cultured; D002908:Chronic Disease; D004847:Epithelial Cells / Q000821:virology; D005260:Female; D015658:HIV Infections / Q000821:virology; D015497:HIV-1 / Q000502:physiology*; D019288:Herpesvirus 8, Human / Q000502:physiology*; D006801:Humans; D008297:Male; D009000:Monocytes / Q000821:virology; D014470:Umbilical Cord / Q000166:cytology; D014775:Virus Activation; D017735:Virus Latency; D014779:Virus Replication