Development of a genetic system and an experimental infection model for marmoset LCV may make it possible to introduce these genes into marmoset LCV in order to directly test whether these viral genes might improve the efficiency of LCV infection in marmosets. recognized by the presence of serum antibodies cross-reactive with viral antigens in EBV-infected B cells (7). As with humans, LCV seropositivity in Old World primates is highly prevalent both in nature and in domesticated colonies, with seropositivity in more than 95% of adult animals (5,7,9). The biology of LCV infection in Old World primates appears to be nearly identical to that of EBV infection in humans (16). This is concordant with the identical repertoire of viral genes and the high degree of sequence homology between EBV and rhesus LCV, a prototype for an Old World LCV whose genome has recently been fully sequenced (11). It was long believed that LCV did not infect New World primates, since there was no strong evidence of EBV cross-reactive antibodies from these species. However, we recently isolated a B-cell-immortalizing herpesvirus from a spontaneous B-cell lymphoma arising in a common marmoset (Callithrix jacchus) that belonged to the LCV genus (2). PCR studies showed that LCV infection was present in three different MK-3207 marmoset colonies, and a similar LCV was also found in squirrel monkeys, indicating that LCV infection is present in species from both major families of New World primates (2). Studies from other laboratories have since confirmed that LCV can be found in a variety of New World species (3,6). The complete genome sequence of the marmoset LCV is striking for its differences from the EBV genome (10). The marmoset LCV encodes at least seven unique open reading frames (ORFs) with no sequence homology to other cell or viral genes. In most cases, there is compelling evidence that these unique genes MK-3207 are predecessors for certain EBV genes, e.g., they are located in the MK-3207 same position of the genome, they have similar transcriptional patterns, they have similar predicted secondary protein structures, or they have similar functional properties demonstrable in vitro. The marmoset LCV also lacks apparent homologs for 14 genes found in EBV and rhesus LCV. These genes are unique to herpesviruses in the LCV genus, i.e., they are not found in other alpha-, beta-, or gamma-2 herpesviruses, and appear to have been acquired in the evolution of LCV from New World primates to humans. Most of these acquired genes are lytic infection genes, and all are nonessential for EBV replication and B-cell immortalization in vitro, suggesting that they play an important role for LCV infection in vivo, rather than in vitro. Thus, the marmoset LCV appears to be a more primitive predecessor of EBV lacking a number of viral genes that have evolved in higher-order primates. Little is known about the biology of LCV infection in New World primates and whether this difference in viral gene repertoire Mouse monoclonal to eNOS results in biologic differences between EBV and marmoset LCV infection. Therefore, we asked whether seroprevalence of LCV infection in New World primates was as high as that seen in Old World primates and humans. We obtained sera from common marmosets at the New England Primate Research Center (NEPRC) and tested them for reactivity to the marmoset LCV ORF59 encoding the small viral capsid antigen (sVCA), p18, or BFRF3 homologue. The carboxy terminus of the sVCA is known to be an immunodominant target in humans and rhesus macaques, and peptides derived from the carboxy terminus of either EBV or rhesus LCV BFRF3 can be used in enzyme immunoassays to detect serologic responses in virtually all LCV-infected humans or rhesus macaques (9,12-15). Therefore, we synthesized a 24-residue peptide from the carboxy terminus of the marmoset ORF59 (Fig.1) and tested sera.