J. Jeong et al., Differential regulation of the overlapping Kaposi's sarcoma-associated herpesvirus vGCR (orf74) and LANA (orf73) promoters, J VIROLOGY, 75(4), 2001, pp. 1798-1807
Similar to that of other herpesviruses, Kaposi's sarcoma-associated herpesv
irus (KSHV/HHV-8) lytic replication destroys the host cell, while the virus
can persist in a latent state in synchrony with the host. During latency o
nly a few genes are transcribed, and the question becomes one of what deter
mines latent versus lytic gene expression. Here we undertake a detailed ana
lysis of the latency-associated nuclear antigen (LANA [orf73]) promoter (LA
NAp). We characterized a minimal region that is necessary and sufficient to
maintain high-level transcription in all tissues tested, including primary
endothelial cells and B cells, which are the suspected natural host for KS
HV. We show that in transient transfection assays LANAp mimics the expressi
on pattern observed for the authentic promoter in the context of the KSHV e
pisome. Unlike other KSHV promoters tested thus far, LANAp is not affected
by tetradecanoyl phorbol acetate or viral lytic cycle functions. It is, how
ever, subject to control by LANA itself and cellular regulatory factors, su
ch as p53. This is in contrast to the K14/vGCR (orf74) promoter, which over
laps LANAp and directs transcription on the opposite strand. We isolated a
minimal cis-regulatory region sufficient for K14/vGCR promoter activity and
show that it, too, mimics the regulation observed for the authentic viral
promoter, In particular, we demonstrate that its activity is absolutely dep
endent on the immediate-early transactivator orf50, the KSHV homolog of the
Epstein-Barr virus Rta transactivator.