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

Debrah A. Fine, Orit Rozenblatt-Rosen, Megha Padi, Anna Korkhin, Robert L. James, Guillaume Adelmant, Rosa Yoon, Luxuan Guo, Christian Berrios, Ying Zhang, Michael A. Calderwood, Soundarapandian Velmurgan, Jingwei Cheng, Jarrod A. Marto, David E. Hill, Michael E. Cusick, Marc Vidal, Laurence Florens, Michael P. Washburn, Larisa LitovchickJames A. DeCaprio

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article numbere1002949
JournalPLoS pathogens
Volume8
Issue number10
DOIs
StatePublished - Oct 2012
Externally publishedYes

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

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