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APOBEC3G Is a p53-Dependent Restriction Factor in Respiratory Syncytial Virus Infection of Human Cells Included in the p53/Immune Axis.
Gladwell, Wesley; Yost, Oriana; Li, Heather; Bell, Whitney J; Chen, Shih-Heng; Ward, James M; Kleeberger, Steven R; Resnick, Michael A; Menendez, Daniel.
Afiliação
  • Gladwell W; Immunity, Inflammation, and Disease Laboratory, National Institute of Environmental Health Sciences, National Institute of Health, Research Triangle Park, Durham, NC 27709, USA.
  • Yost O; Immunity, Inflammation, and Disease Laboratory, National Institute of Environmental Health Sciences, National Institute of Health, Research Triangle Park, Durham, NC 27709, USA.
  • Li H; Immunity, Inflammation, and Disease Laboratory, National Institute of Environmental Health Sciences, National Institute of Health, Research Triangle Park, Durham, NC 27709, USA.
  • Bell WJ; Immunity, Inflammation, and Disease Laboratory, National Institute of Environmental Health Sciences, National Institute of Health, Research Triangle Park, Durham, NC 27709, USA.
  • Chen SH; Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institute of Health, Research Triangle Park, Durham, NC 27709, USA.
  • Ward JM; Viral Vector Core Facility, National Institute of Environmental Health Sciences, National Institute of Health, Research Triangle Park, Durham, NC 27709, USA.
  • Kleeberger SR; Integrative Bioinformatics Support Group, National Institute of Environmental Health Sciences, National Institute of Health, Research Triangle Park, Durham, NC 27709, USA.
  • Resnick MA; Immunity, Inflammation, and Disease Laboratory, National Institute of Environmental Health Sciences, National Institute of Health, Research Triangle Park, Durham, NC 27709, USA.
  • Menendez D; Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institute of Health, Research Triangle Park, Durham, NC 27709, USA.
Int J Mol Sci ; 24(23)2023 Nov 27.
Article em En | MEDLINE | ID: mdl-38069117
ABSTRACT
Identifying and understanding genetic factors that influence the propagation of the human respiratory syncytial virus (RSV) can lead to health benefits and possibly augment recent vaccine approaches. We previously identified a p53/immune axis in which the tumor suppressor p53 directly regulates the expression of immune system genes, including the seven members of the APOBEC3 family of DNA cytidine deaminases (A3), which are innate immune sentinels against viral infections. Here, we examined the potential p53 and A3 influence in RSV infection, as well as the overall p53-dependent cellular and p53/immune axis responses to infection. Using a paired p53 model system of p53+ and p53- human lung tumor cells, we found that RSV infection activates p53, leading to the altered p53-dependent expression of A3D, A3F, and A3G, along with p53 site-specific binding. Focusing on A3G because of its 10-fold-greater p53 responsiveness to RSV, the overexpression of A3G can reduce RSV viral replication and syncytial formation. We also observed that RSV-infected cells undergo p53-dependent apoptosis. The study was expanded to globally address at the transcriptional level the p53/immune axis response to RSV. Nearly 100 genes can be directly targeted by the p53/immune axis during RSV infection based on our p53BAER analysis (Binding And Expression Resource). Overall, we identify A3G as a potential p53-responsive restriction factor in RSV infection. These findings have significant implications for RSV clinical and therapeutic studies and other p53-influenced viral infections, including using p53 adjuvants to boost the response of A3 genes.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Vírus Sincicial Respiratório Humano / Infecções por Vírus Respiratório Sincicial Limite: Humans Idioma: En Revista: Int J Mol Sci Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Vírus Sincicial Respiratório Humano / Infecções por Vírus Respiratório Sincicial Limite: Humans Idioma: En Revista: Int J Mol Sci Ano de publicação: 2023 Tipo de documento: Article