During latency, Kaposi's sarcoma-associated herpesvirus (KSHV) is thought to replicate once and to be partitioned in synchrony with the cell cycle of the host. In this replication cycle, the KSHV terminal repeat (TR) sequence functions as a replication origin, assisted by the latency-associated nuclear antigen (LANA). Thus, TR seems to function as a cis element for the replication and partitioning of the KSHV genome. Viral replication and partitioning are also likely to require cellular factors that interact with TR in either a LANAdependent or -independent manner. Here, we sought to identify factors that associate with TR by using a TR DNA column and found that poly(ADP-ribose) polymerase 1 (PARP1) and known replication factors, including ORC2, CDC6, and Mcm7, bound to TR. PARP1 bound directly to a specific region within TR independent of LANA, and LANA was poly(ADP-ribosyl)ated by PARP1. Drugs such as hydroxyurea and niacinamide, which raise or lower PARP activity, respectively, affected the virus copy number in infected cells. Thus, the poly(ADPribosyl)ation status of LANA appears to affect the replication and/or maintenance of the viral genome. Drugs that specifically up-regulate PARP activity may lead to the disappearance of latent KSHV.Kaposi's sarcoma-associated herpesvirus (KSHV) or human herpesvirus 8 (HHV8) was discovered in Kaposi's sarcoma lesions (12) and is strongly associated with multicentric Castleman's disease and primary effusion lymphomas, which are predominantly found in AIDS patients (9). KSHV belongs to the gammaherpesviruses, and most of the virus is in the latent phase in these diseases (13).Epstein-Barr virus (EBV), another human gammaherpesvirus, also establishes latency and is associated with epithelial and many kinds of lymphoid tumors (28). Several genes with potential oncogenic activity, latency-associated nuclear antigen (LANA), K-cyclin (ORF72), vFLIP (ORF71), K15, and LANA2 (vIRF3) of KSHV (17,20,46,55) and EBNA1, LMP1, LMP2, and EBER of EBV (40), are expressed during latency, and the presence of the virus seems to be a minimum requirement for cancer formation (10) and to be tightly linked to the growth activity of the virus-positive B-cell lymphoma lines. Therefore, even in the context of serious disease, control of the latent infection itself could be an important strategy in treatment of these cancers.In latent replication, the KSHV genome is thought to replicate once per cell cycle, in synchrony with the host replication machinery, as reported for EBV (1,27,54). Recent studies of KSHV latent replication and maintenance have revealed that (i) the terminal repeat sequence functions as a replication origin (3, 4) and (ii) LANA binds to a specific sequence within the terminal repeat (TR) and is an essential viral gene product for latent viral replication (3,4,27). These two facts are important for understanding how the KSHV genome replicates in the latent phase. In fact, the two viral components TR and LANA appeared to be sufficient to execute viral replication in a transient t...

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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.

ABSTRACT. Serum samples from 191 ostriches (Struthio camelus) in Japan were tested for antibodies to Newcastle disease virus (NDV) and avian influenza virus (AIV). Twenty-two (12%) contained NDV-specific neutralizing antibodies by a virus-neutralization (VN) test without vaccination. Antibodies to AIV were not detected in the any sera by an agar gel precipitation test. Seven serum samples that had vaccinated with live NDV by eye drop were all positive by the VN test at 1 month post vaccination. A haemagglutination inhibition (HI) test for NDV seemed not to be suitable for ostriches because of non-specific agglutination of chicken red blood cells. No haemagglutinating viruses were isolated. This is the first report on detection of antibodies against NDV in ostriches in Japan. KEY WORDS: Newcastle disease, ostrich, serological survey.

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