Details

Autor(en) / Beteiligte

• Shire, Kathy
• Marcon, Edyta
• Greenblatt, Jack
• Frappier, Lori

Titel

Characterization of a cancer-associated Epstein-Barr virus EBNA1 variant reveals a novel interaction with PLOD1 and PLOD3

Ist Teil von

• Virology (New York, N.Y.), 2021-10, Vol.562, p.103-109

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2021

Link zum Volltext

Quelle

Electronic Journals Library

Beschreibungen/Notizen

• Whole genome sequence analysis of Epstein-Barr virus genomes from tumours and healthy individuals identified three amino acid changes in EBNA1 that are strongly associated with gastric carcinoma and nasopharyngeal carcinoma. Here we show that, while these mutations do not impact EBNA1 plasmid maintenance function, one of them (Thr85Ala) decreases transcriptional activation and results in a gain of function interaction with PLOD1 and PLOD3. PLOD family proteins are strongly linked to multiple cancers, and PLOD1 is recognized as a prognostic marker of gastric carcinoma. We identified the PLOD1 binding site in EBNA1as the N-terminal transactivation domain and show that lysine 83 is critical for this interaction. The results provide a novel link between EBV infection and the cancer-associated PLOD proteins. •Specific changes in EBNA1 have been identified in Epstein-Barr virus isolates from gastric and nasopharyngeal carcinomas.•EBNA1 T85A amino acid change decreases the transcriptional activation activity of EBNA1.•EBNA1 T85A amino acid change promotes EBNA1 binding to PLOD1.•PLOD1 binds EBNA1 through EBNA1's N-terminal transcriptional activation domain and is dependent on K83.