| Title | Persistent KSHV Infection Increases EBV-Associated Tumor Formation In Vivo via Enhanced EBV Lytic Gene Expression. |
| Publication Type | Journal Article |
| Year of Publication | 2017 |
| Authors | McHugh D, Caduff N, Barros MHenrique M, Rämer PC, Raykova A, Murer A, Landtwing V, Quast I, Styles CT, Spohn M, Fowotade A, Delecluse H-J, Papoudou-Bai A, Lee Y-M, Kim J-M, Middeldorp J, Schulz TF, Cesarman E, Zbinden A, Capaul R, White RE, Allday MJ, Niedobitek G, Blackbourn DJ, Grundhoff A, Münz C |
| Journal | Cell Host Microbe |
| Volume | 22 |
| Issue | 1 |
| Pagination | 61-73.e7 |
| Date Published | 2017 Jul 12 |
| ISSN | 1934-6069 |
| Keywords | Animals, B-Lymphocytes, Cell Line, Tumor, Coinfection, Cytokines, Disease Models, Animal, DNA, Viral, Epstein-Barr Virus Infections, Gene Expression Regulation, Viral, Genes, Viral, Herpesviridae Infections, Herpesvirus 4, Human, Herpesvirus 8, Human, High-Throughput Nucleotide Sequencing, Humans, Lymphoma, Primary Effusion, Mice, Neoplasms, Spleen, Survival Rate, Virus Replication |
| Abstract | The human tumor viruses Epstein-Barr virus (EBV) and Kaposi sarcoma-associated herpesvirus (KSHV) establish persistent infections in B cells. KSHV is linked to primary effusion lymphoma (PEL), and 90% of PELs also contain EBV. Studies on persistent KSHV infection in vivo and the role of EBV co-infection in PEL development have been hampered by the absence of small animal models. We developed mice reconstituted with human immune system components as a model for KSHV infection and find that EBV/KSHV dual infection enhanced KSHV persistence and tumorigenesis. Dual-infected cells displayed a plasma cell-like gene expression pattern similar to PELs. KSHV persisted in EBV-transformed B cells and was associated with lytic EBV gene expression, resulting in increased tumor formation. Evidence of elevated lytic EBV replication was also found in EBV/KSHV dually infected lymphoproliferative disorders in humans. Our data suggest that KSHV augments EBV-associated tumorigenesis via stimulation of lytic EBV replication. |
| DOI | 10.1016/j.chom.2017.06.009 |
| Alternate Journal | Cell Host Microbe |
| PubMed ID | 28704654 |
| Grant List | 14-1033 / AICR_ / Worldwide Cancer Research / United Kingdom |
Related Faculty:
Ethel Cesarman, M.D., Ph.D.