A posttranscriptional regulator of Kaposi's sarcoma-associated herpesvirus interacts with RNA-binding protein PCBP1 and controls gene expression through the IRES

Kaposi's sarcoma-associated herpesvirus (KSHV; also known as human herpesvirus 8, HHV-8) belongs to the gamma-herpesvirus subfamily. The KSHV ORF57 gene is thought to be a homolog of posttranscriptional regulators that are conserved in the herpesvirus family and are essential for replication. We generated specific monoclonal antibodies (mAbs) against the ORF57 protein that detected the 51-kDa protein expressed in the nucleus of KSHV-infected cells. We also found that the ORF57 protein interacted with poly(rC)-binding protein 1 (PCBP1), a cellular RNA-binding, posttranscriptional regulator. ORF57's interaction with PCBP1 enhanced the activity of not only poliovirus internal ribosome-entry site (IRES)-dependent translation but also X-linked inhibitor of apoptosis (XIAP) and KSHV vFLIP IRES. Actually, when ORF57 expression was induced by the expression of replication and transcription activator (RTA) in KSHV-infected cells, the expression of XIAP was enhanced. These results suggest that ORF57 binds to PCBP1 as a functional partner for posttranscriptional regulation and is involved in the regulation of the expression of both cellular and viral genes through IRESs. (C) 2004 Elsevier Inc. All rights reserved.