RESUMO
Epstein-Barr virus (EBV) is implicated in the development of human B cell lymphomas and carcinomas. Although related oncogenic herpesviruses were believed to be endemic only in Old World primate species, we now find these viruses to be endemic in New World primates. We have isolated a transforming, EBV-related virus from spontaneous B cell lymphomas of common marmosets (Callithrix jacchus). Sequencing of two-thirds of the genome reveals considerable divergence from the genomes of EBV and Old World primate EBV-related viruses, including differences in genes important for virus-induced cell growth transformation and pathogenesis. DNA related to the C. jacchus herpesvirus is frequently detected in squirrel monkey peripheral blood lymphocytes, indicating that persistent infection with EBV-related viruses is prevalent in both New World primate families. Understanding how these more divergent EBV-related viruses achieve similar biologic outcomes in their natural host is likely to provide important insights into EBV infection, B cell growth transformation, and oncogenesis.
Assuntos
Gammaherpesvirinae/classificação , Gammaherpesvirinae/genética , Herpesvirus Humano 4/genética , Linfoma de Células B/veterinária , Doenças dos Primatas/virologia , Sequência de Aminoácidos , Animais , Callithrix , Clonagem Molecular , DNA Viral/genética , Gammaherpesvirinae/isolamento & purificação , Variação Genética , Genoma Viral , Glutationa Transferase/genética , Herpesvirus Humano 4/classificação , Herpesvirus Humano 4/isolamento & purificação , Herpesvirus Humano 8/genética , Humanos , Linfoma de Células B/virologia , Dados de Sequência Molecular , Fases de Leitura Aberta , Filogenia , Saimiri , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Transfecção , Células Tumorais CultivadasRESUMO
Latent membrane protein 2B (LMP2B) is expressed during latent Epstein-Barr virus (EBV) infection, but little is known about its role. The goal of this study was to determine whether an LMP2B homologue is conserved in the rhesus monkey lymphocryptovirus (LCV). Both rhesus LCV LMP2A and LMP2B genes were cloned and sequenced. The rhesus LCV LMP2B gene is positionally conserved, and the EBNA-2 responsiveness and the bidirectional nature of the LMP1-LMP2B promoter have also been functionally conserved. However, this region of the genome encoding the LMP1, LMP1-LMP2B promoter, and LMP2B first exon demonstrates the most dramatic nucleotide sequence divergence between human and nonhuman LCV observed to date. Evolution of the rhesus LCV LMP2B promoter and transcript despite the dynamic nature of this genomic region reflects strong selective pressure for a yet-to-be-identified LMP2B function.
