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Poly(ADP-ribose) polymerase 1 promotes transcriptional repression of integrated retroviruses.
Bueno, Murilo T D; Reyes, Daniel; Valdes, Luis; Saheba, Adarsh; Urias, Eduardo; Mendoza, Crystal; Fregoso, Oliver I; Llano, Manuel.
Afiliación
  • Bueno MT; Department of Biological Sciences, University of Texas at El Paso, El Paso, Texas, USA.
J Virol ; 87(5): 2496-507, 2013 Mar.
Article en En | MEDLINE | ID: mdl-23255787
Poly(ADP-ribose) polymerase 1 (PARP-1) is a cellular enzyme with a fundamental role in DNA repair and the regulation of chromatin structure, processes involved in the cellular response to retroviral DNA integration. However, the function of PARP-1 in retroviral DNA integration is controversial, probably due to the functional redundancy of the PARP family in mammalian cells. We evaluated the function of PARP-1 in retroviral infection using the chicken B lymphoblastoid cell line DT40. These cells lack significant PARP-1 functional redundancy and efficiently support the postentry early events of the mammalian-retrovirus replication cycle. We observed that DT40 PARP-1(-/-) cells were 9- and 6-fold more susceptible to infection by human immunodeficiency virus type 1 (HIV-1)- and murine leukemia virus (MLV)-derived viral vectors, respectively, than cells expressing PARP-1. Production of avian Rous-associated virus type 1 was also impaired by PARP-1. However, the susceptibilities of these cell lines to infection by the nonretrovirus vesicular stomatitis virus were indistinguishable. Real-time PCR analysis of the HIV-1 life cycle demonstrated that PARP-1 did not impair reverse transcription, nuclear import of the preintegration complex, or viral DNA integration, suggesting that PARP-1 regulates a postintegration step. In support of this hypothesis, pharmacological inhibition of the epigenetic mechanism of transcriptional silencing increased retroviral expression in PARP-1-expressing cells, suppressing the differences observed. Further analysis of the implicated molecular mechanism indicated that PARP-1-mediated retroviral silencing requires the C-terminal region, but not the enzymatic activity, of the protein. In sum, our data indicate a novel role of PARP-1 in the transcriptional repression of integrated retroviruses.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Retroviridae / Transcripción Genética / Replicación Viral / Poli(ADP-Ribosa) Polimerasas Límite: Animals / Humans Idioma: En Revista: J Virol Año: 2013 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Retroviridae / Transcripción Genética / Replicación Viral / Poli(ADP-Ribosa) Polimerasas Límite: Animals / Humans Idioma: En Revista: J Virol Año: 2013 Tipo del documento: Article País de afiliación: Estados Unidos