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A paralogous pair of mammalian host restriction factors form a critical host barrier against poxvirus infection.
Meng, Xiangzhi; Zhang, Fushun; Yan, Bo; Si, Chuanping; Honda, Hiroaki; Nagamachi, Akiko; Sun, Lu-Zhe; Xiang, Yan.
Afiliação
  • Meng X; Department of Microbiology, Immunology and Molecular Genetics, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America.
  • Zhang F; Institute of Immunology and Molecular Medicine, Jining Medical College, Jining, Shandong, China.
  • Yan B; Department of Microbiology, Immunology and Molecular Genetics, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America.
  • Si C; Department of Microbiology, Immunology and Molecular Genetics, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America.
  • Honda H; Institute of Immunology and Molecular Medicine, Jining Medical College, Jining, Shandong, China.
  • Nagamachi A; Institute of Laboratory Animals, Tokyo Women's Medical University, Shinjuku-ku, Tokyo, Japan.
  • Sun LZ; Department of Molecular Oncology and Leukemia Program Project, Hiroshima University, Minami-ku, Hiroshima, Japan.
  • Xiang Y; Department of Cell Systems & Anatomy, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America.
PLoS Pathog ; 14(2): e1006884, 2018 02.
Article em En | MEDLINE | ID: mdl-29447249
Host restriction factors constitute a formidable barrier for viral replication to which many viruses have evolved counter-measures. Human SAMD9, a tumor suppressor and a restriction factor for poxviruses in cell lines, is antagonized by two classes of poxvirus proteins, represented by vaccinia virus (VACV) K1 and C7. A paralog of SAMD9, SAMD9L, is also encoded by some mammals, while only one of two paralogs is retained by others. Here, we show that SAMD9L functions similarly to SAMD9 as a restriction factor and that the two paralogs form a critical host barrier that poxviruses must overcome to establish infection. In mice, which naturally lack SAMD9, overcoming SAMD9L restriction with viral inhibitors is essential for poxvirus replication and pathogenesis. While a VACV deleted of both K1 and C7 (vK1L-C7L-) was restricted by mouse cells and highly attenuated in mice, its replication and virulence were completely restored in SAMD9L-/- mice. In humans, both SAMD9 and SAMD9L are poxvirus restriction factors, although the latter requires interferon induction in many cell types. While knockout of SAMD9 with Crispr-Cas9 was sufficient for abolishing the restriction for vK1L-C7L- in many human cells, knockout of both paralogs was required for abolishing the restriction in interferon-treated cells. Both paralogs are antagonized by VACV K1, C7 and C7 homologs from diverse mammalian poxviruses, but mouse SAMD9L is resistant to the C7 homolog encoded by a group of poxviruses with a narrow host range in ruminants, indicating that host species-specific difference in SAMD9/SAMD9L genes serves as a barrier for cross-species poxvirus transmission.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Poxviridae / Proteínas / Infecções por Poxviridae / Proteínas Supressoras de Tumor / Especificidade de Hospedeiro Limite: Animals / Humans Idioma: En Revista: PLoS Pathog Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Poxviridae / Proteínas / Infecções por Poxviridae / Proteínas Supressoras de Tumor / Especificidade de Hospedeiro Limite: Animals / Humans Idioma: En Revista: PLoS Pathog Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Estados Unidos