Identification of FAM111A as an SV40 Host Range Restriction and Adenovirus Helper Factor

PLoS Pathogens

Jarrod A. Marto¹  Rosa Yoon²  Soundarapandian Velmurgan³  David E. Hill⁴  Luxuan Guo⁵  Michael E. Cusick⁶  Laurence Florens⁶  Anna Korkhin⁶  Larisa Litovchick⁶  Debrah A. Fine⁶  Christian Berrios⁶  Michael P. Washburn⁷  Jingwei Cheng⁸  Megha Padi⁸  Ying Zhang⁸  Robert L. James⁸  Guillaume Adelmant⁸  Michael A. Calderwood⁸  James A. DeCaprio⁹  Orit Rozenblatt-Rosen⁹  Marc Vidal⁹ 

[1] Blais Proteomics Center and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America;Center for Cancer Computational Biology, Department of Biostatistics and Computational Biology and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America;Center for Cancer Systems Biology and Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America;Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, United States of America;Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, United States of America;Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America;Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America;Genomic Analysis of Network Perturbations Center of Excellence in Genomic Science, Center for Cancer Systems Biology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America;Program in Virology, Harvard University Graduate School of Arts and Sciences, Division of Medical Sciences, Boston, Massachusetts, United States of America

关键词: Virus effects on host gene expression;    SV40;    Immunoprecipitation;    Viral gene expression;    Gene expression;    Infectious disease control;    DNA-binding proteins;    Viral replication;   

DOI  :  10.1371/journal.ppat.1002949

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

The small genome of polyomaviruses encodes a limited number of proteins that are highly dependent on interactions with host cell proteins for efficient viral replication. The SV40 large T antigen (LT) contains several discrete functional domains including the LXCXE or RB-binding motif, the DNA binding and helicase domains that contribute to the viral life cycle. In addition, the LT C-terminal region contains the host range and adenovirus helper functions required for lytic infection in certain restrictive cell types. To understand how LT affects the host cell to facilitate viral replication, we expressed full-length or functional domains of LT in cells, identified interacting host proteins and carried out expression profiling. LT perturbed the expression of p53 target genes and subsets of cell-cycle dependent genes regulated by the DREAM and the B-Myb-MuvB complexes. Affinity purification of LT followed by mass spectrometry revealed a specific interaction between the LT C-terminal region and FAM111A, a previously uncharacterized protein. Depletion of FAM111A recapitulated the effects of heterologous expression of the LT C-terminal region, including increased viral gene expression and lytic infection of SV40 host range mutants and adenovirus replication in restrictive cells. FAM111A functions as a host range restriction factor that is specifically targeted by SV40 LT.

【 授权许可】

CC BY