Persistent infection of Epstein-Barr virus-positive B lymphocytes by human herpesvirus 8.
In patients with Kaposi's sarcoma (KS), human herpesvirus 8 (HHV-8) can invariably be detected in KS tumor tissue and, at a lower frequency, in prostate tissue and peripheral blood B lymphocytes. Whereas the majority of KS spindle cells are latently infected by HHV-8, linear HHV-8 genomes characteristic for lytic infection are found predominantly in the peripheral blood cells of KS patients. In this study, we show that HHV-8 can stably infect B lymphocytes in vitro in the presence of Epstein-Barr virus (EBV). We were able to generate immortalized HHV-8(+)/EBV+ lymphoblastoid cell lines (LCLs) derived from peripheral blood mononuclear cells (PBMC) of EBV- and EBV+ donors. In HHV-8(+)/EBV+ LCLs, which have the phenotype of activated B lymphocytes (CD19(+), surface immunoglobulin M, CD23(+), CD30(+), CD80(+)), HHV-8 was still present after more than 25 passages (more than 9 months of culture). Latent viral transcripts and proteins were present in nonstimulated HHV-8(+)/EBV+ LCLs. After induction by phorbol ester and n-butyrate, HHV-8(+)/EBV+ LCLs expressed lytic HHV-8 transcripts and proteins. Moreover, HHV-8 could be serially passaged from HHV-8(+)/EBV+ LCLs to fresh PBMC.
Kliche
S
S
Max-von-Pettenkofer Institut, Genzentrum, Universität München, 81377 Munich, GSF Forschungszentrum, 80377 Munich, Germany.
Kremmer
E
E
Hammerschmidt
W
W
Koszinowski
U
U
Haas
J
J
D001402:B-Lymphocytes / Q000821:virology*; D002461:Cell Line, Transformed; D004854:Herpesvirus 4, Human / Q000302:isolation & purification*; D019288:Herpesvirus 8, Human / Q000472:pathogenicity* / Q000502:physiology; D006801:Humans; D010641:Phenotype; D012692:Serial Passage; D014764:Viral Proteins / Q000096:biosynthesis; D017735:Virus Latency
D014764:Viral Proteins