Human herpesvirus-8 (Kaposi's sarcoma-associated virus) ORF50 increases in vitro cell susceptibility to human immunodeficiency virus type 1 infection.
ORF50, an immediate-early gene of human herpesvirus-8 (HHV-8), encodes a transactivating protein necessary for virus reactivation and lytic replication. ORF50 was reported recently to synergize with human immunodeficiency virus type 1 (HIV-1) tat at a post-transcriptional level. To study the effects of these molecular interactions on HIV replication and biology, cellular clones stably transformed with ORF50 were obtained by transfection of cell lines of different origin. These clones were infected subsequently with HIV. Experiments showed that ORF50 enhances HIV replication in T and B cells (Jurkat and BC-3 cells) and induces susceptibility and transient permissiveness in non-susceptible glial (A172) cells. Upregulation of viral receptors and co-receptors did not account for increased sensitivity to HIV infection and therefore the action of ORF50 might be modulated by the intracellular environment. Interestingly, non-susceptible cells transformed with ORF50 showed transient production of HIV particles that could spread to adjacent cells by direct contact. These findings show that HHV-8 ORF50 has an enhancing effect on HIV replication in vitro and suggest that the two viruses might interact in co-infected patients.
Caselli
Elisabetta
E
Section of Microbiology, Department of Experimental and Diagnostic Medicine, University of Ferrara, Via Borsari 46, 44100 Ferrara, Italy.
Galvan
Monica
M
Section of Microbiology, Department of Experimental and Diagnostic Medicine, University of Ferrara, Via Borsari 46, 44100 Ferrara, Italy.
Santoni
Fabio
F
Section of Microbiology, Department of Experimental and Diagnostic Medicine, University of Ferrara, Via Borsari 46, 44100 Ferrara, Italy.
Rotola
Antonella
A
Section of Microbiology, Department of Experimental and Diagnostic Medicine, University of Ferrara, Via Borsari 46, 44100 Ferrara, Italy.
Caruso
Arnaldo
A
Institute of Microbiology, University of Brescia Medical School, Brescia, Italy.
Cassai
Enzo
E
Section of Microbiology, Department of Experimental and Diagnostic Medicine, University of Ferrara, Via Borsari 46, 44100 Ferrara, Italy.
Luca
Dario Di
DD
Section of Microbiology, Department of Experimental and Diagnostic Medicine, University of Ferrara, Via Borsari 46, 44100 Ferrara, Italy.
D001402:B-Lymphocytes / Q000821:virology; D002460:Cell Line; D015658:HIV Infections / Q000821:virology; D015497:HIV-1 / Q000472:pathogenicity* / Q000502:physiology; D019288:Herpesvirus 8, Human / Q000378:metabolism*; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D019169:Jurkat Cells / Q000821:virology; D009457:Neuroglia / Q000821:virology; D015728:Receptors, HIV / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D014162:Transfection; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects*
D017874:Immediate-Early Proteins; D015728:Receptors, HIV; C417604:Rta protein, Human herpesvirus 8; D015534:Trans-Activators; D014764:Viral Proteins