title: Identification of FAM111A as an SV40 host range restriction and adenovirus helper factor.
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.
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
authors.forename: Debrah A
authors.initials: DA
authors.lastname: Fine
authors.forename: Orit
authors.initials: O
authors.lastname: Rozenblatt-Rosen
authors.forename: Megha
authors.initials: M
authors.lastname: Padi
authors.forename: Anna
authors.initials: A
authors.lastname: Korkhin
authors.forename: Robert L
authors.initials: RL
authors.lastname: James
authors.forename: Guillaume
authors.initials: G
authors.lastname: Adelmant
authors.forename: Rosa
authors.initials: R
authors.lastname: Yoon
authors.forename: Luxuan
authors.initials: L
authors.lastname: Guo
authors.forename: Christian
authors.initials: C
authors.lastname: Berrios
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Michael A
authors.initials: MA
authors.lastname: Calderwood
authors.forename: Soundarapandian
authors.initials: S
authors.lastname: Velmurgan
authors.forename: Jingwei
authors.initials: J
authors.lastname: Cheng
authors.forename: Jarrod A
authors.initials: JA
authors.lastname: Marto
authors.forename: David E
authors.initials: DE
authors.lastname: Hill
authors.forename: Michael E
authors.initials: ME
authors.lastname: Cusick
authors.forename: Marc
authors.initials: M
authors.lastname: Vidal
authors.forename: Laurence
authors.initials: L
authors.lastname: Florens
authors.forename: Michael P
authors.initials: MP
authors.lastname: Washburn
authors.forename: Larisa
authors.initials: L
authors.lastname: Litovchick
authors.forename: James A
authors.initials: JA
authors.lastname: DeCaprio
mesh_terms: D000256:Adenoviridae; D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002522:Chlorocebus aethiops; D020869:Gene Expression Profiling; D058507:Host Specificity / Q000235:genetics*; D006801:Humans; D051605:Kv Channel-Interacting Proteins / Q000378:metabolism; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D034741:RNA, Small Interfering; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism; D013539:Simian virus 40 / Q000472:pathogenicity*; D015534:Trans-Activators / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics; D014779:Virus Replication
chemical_list: D000952:Antigens, Polyomavirus Transforming; D018797:Cell Cycle Proteins; C579415:FAM111A protein, human; C496749:KCNIP3 protein, human; D051605:Kv Channel-Interacting Proteins; C064352:MYBL2 protein, human; D034741:RNA, Small Interfering; D011991:Receptors, Virus; D012097:Repressor Proteins; D015534:Trans-Activators; D016159:Tumor Suppressor Protein p53