Transient expression of human herpesvirus-8 (Kaposi's sarcoma-associated herpesvirus) ORF50 enhances HIV-1 replication.
OBJECTIVE
Human herpesvirus 8 (HHV-8) is the etiologic agent of Kaposi's sarcoma, the most common neoplasm in patients with acquired immunodeficiency syndrome. Current evidence indicates that activation of viral replication may be critical to the development of the disease. A key factor in the induction of HHV-8 lytic replication is ORF50, an immediate-early gene encoding a transactivating protein necessary for viral reactivation. We recently reported that ORF50 synergizes with HIV-1 TAT at a post-transcriptional level. To study the effects of these molecular interactions upon HIV replication and biology, cell lines of different origin were transiently transfected with ORF50 and subsequently infected with HIV.


METHODS
Jurkat, BCBL-1 and A172 cells were transfected with ORF50 and subsequently infected with different MOI of HIV. The development of infection was evaluated by analyzing p24 antigen release, production of infectious HIV particles and the presence and transcription of HIV proviral DNA.


RESULTS
ORF50 induced increased levels of HIV replication and production in CD4+ Jurkat T cells. Transfection of ORF50 into nonsusceptible B and glial cells (BCBL-1 and A172, respectively) increased cell susceptibility to infection and resulted in transient permissiveness to HIV replication.


CONCLUSIONS
HIV replication can be significantly affected by the presence of HHV-8. Expression of ORF50 increases the efficiency of HIV infection in different cell types. This potentially could result in enhanced HIV spread within the infected organism and faster progression of the disease.
Caselli
Elisabetta
E
Department of Experimental and Diagnostic Medicine, Section of Microbiology, University of Ferrara, Ferrara, Italy.
Galvan
Monica
M
Cassai
Enzo
E
Di Luca
Dario
D
D001402:B-Lymphocytes / Q000821:virology; D002460:Cell Line; D015967:Gene Expression Regulation, Viral; D015658:HIV Infections / Q000821:virology; D015497:HIV-1 / Q000472:pathogenicity / Q000502:physiology*; D019288:Herpesvirus 8, Human / Q000502:physiology*; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism; D019169:Jurkat Cells / Q000821:virology; D009457:Neuroglia / Q000821:virology; D016366:Open Reading Frames / Q000235:genetics / Q000502:physiology*; D014162:Transfection; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D014775:Virus Activation; D014779:Virus Replication
D017874:Immediate-Early Proteins; D014764:Viral Proteins