RESUMO
Primary effusion lymphoma (PEL) is an AIDS-defining cancer. All PELs carry Kaposi sarcoma-associated herpesvirus (KSHV). X chromosome-targeted sequencing of PEL identified 34 common missense mutations in 100% of cases. This included a Phe196Ser change in the interleukin 1 receptor-associated kinase 1 (IRAK1). The mutation was verified in primary PEL exudates. IRAK1 is the binding partner of MyD88, which is mutated in a fraction of Waldenström macroglobulinemia. Together, these two mediate toll-like receptor (TLR) signaling. IRAK1 was constitutively phosphorylated in PEL and required for survival, implicating IRAK1 and TLR signaling as a driver pathway in PEL and as a new drug development target.
Assuntos
Infecções por Herpesviridae/metabolismo , Herpesvirus Humano 8 , Quinases Associadas a Receptores de Interleucina-1/metabolismo , Linfoma de Efusão Primária/metabolismo , Mutação , Proteínas de Neoplasias/metabolismo , Transdução de Sinais , Linhagem Celular Tumoral , Infecções por Herpesviridae/genética , Infecções por Herpesviridae/patologia , Humanos , Quinases Associadas a Receptores de Interleucina-1/genética , Linfoma de Efusão Primária/genética , Linfoma de Efusão Primária/patologia , Linfoma de Efusão Primária/virologia , Fator 88 de Diferenciação Mieloide/genética , Fator 88 de Diferenciação Mieloide/metabolismo , Proteínas de Neoplasias/genética , Receptores Toll-Like/genética , Receptores Toll-Like/metabolismo , Macroglobulinemia de Waldenstrom/genética , Macroglobulinemia de Waldenstrom/metabolismo , Macroglobulinemia de Waldenstrom/patologiaRESUMO
Cytomegalovirus displays genetic heterogeneity, which has implications for antiviral and vaccine development. Many studies have focused on laboratory isolates that have been extensively adapted for growth on fibroblasts. Here, we report whole-genome sequences for 10 human cytomegalovirus (HCMV) strains that readily grow on ARPE-19 human retinal pigment epithelial cells.
RESUMO
The complete genome sequences of Mandrillus leucophaeus and Papio ursinus cytomegaloviruses were determined. An isolate from a drill monkey, OCOM6-2, and an isolate from a chacma baboon, OCOM4-52, were subjected to pyrosequencing and assembled. Comparative alignment of published primate cytomegaloviruses (CMVs) showed variable sequence conservation between species.
Assuntos
Papillomaviridae/genética , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/epidemiologia , Profissionais do Sexo/estatística & dados numéricos , Adulto , Estudos de Coortes , Feminino , Genótipo , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Soronegatividade para HIV , Soropositividade para HIV , Humanos , Incidência , Quênia/epidemiologia , Estudos Longitudinais , Pessoa de Meia-Idade , Teste de Papanicolaou , Papillomaviridae/classificação , Infecções por Papillomavirus/diagnóstico , Reação em Cadeia da Polimerase , Prevalência , Neoplasias do Colo do Útero/epidemiologia , Displasia do Colo do Útero/epidemiologiaRESUMO
The complete genome sequence of attenuated guinea pig cytomegalovirus cloned as bacterial artificial chromosome N13R10 was determined. Comparison to pathogenic salivary gland-derived virus revealed 13 differences, 1 of which disrupted overlapping open reading frames encoding GP129 and GP130. Attenuation of N13R10 may arise from an inability to express GP129 and/or GP130.