Identification of FAM111A as an SV40 host range restriction and adenovirus helper factor.
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 bindi...
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Public Library of Science (PLoS)
2012
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oai:doaj.org-article:a9e10f059bbc4812825aacead026779d2021-11-18T06:06:27ZIdentification of FAM111A as an SV40 host range restriction and adenovirus helper factor.1553-73661553-737410.1371/journal.ppat.1002949https://doaj.org/article/a9e10f059bbc4812825aacead026779d2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23093934/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374The 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.Debrah A FineOrit Rozenblatt-RosenMegha PadiAnna KorkhinRobert L JamesGuillaume AdelmantRosa YoonLuxuan GuoChristian BerriosYing ZhangMichael A CalderwoodSoundarapandian VelmurganJingwei ChengJarrod A MartoDavid E HillMichael E CusickMarc VidalLaurence FlorensMichael P WashburnLarisa LitovchickJames A DeCaprioPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 8, Iss 10, p e1002949 (2012) |
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DOAJ |
| collection |
DOAJ |
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| topic |
Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 |
| spellingShingle |
Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 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 Litovchick James A DeCaprio Identification of FAM111A as an SV40 host range restriction and adenovirus helper factor. |
| description |
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. |
| format |
article |
| author |
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 Litovchick James A DeCaprio |
| author_facet |
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 Litovchick James A DeCaprio |
| author_sort |
Debrah A Fine |
| title |
Identification of FAM111A as an SV40 host range restriction and adenovirus helper factor. |
| title_short |
Identification of FAM111A as an SV40 host range restriction and adenovirus helper factor. |
| title_full |
Identification of FAM111A as an SV40 host range restriction and adenovirus helper factor. |
| title_fullStr |
Identification of FAM111A as an SV40 host range restriction and adenovirus helper factor. |
| title_full_unstemmed |
Identification of FAM111A as an SV40 host range restriction and adenovirus helper factor. |
| title_sort |
identification of fam111a as an sv40 host range restriction and adenovirus helper factor. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2012 |
| url |
https://doaj.org/article/a9e10f059bbc4812825aacead026779d |
| work_keys_str_mv |
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| _version_ |
1718424559779053568 |