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. McHugh et al. describe a small animal model of KSHV infection and demonstrate that KSHV collaborates with another human gamma herpes virus, EBV, to establish persistent infection in B cells. The emerging transformed cells resemble primary effusion lymphomas, the malignancies that frequently harbor both viruses in humans.
| Original language | English |
|---|---|
| Pages (from-to) | 61-73.e7 |
| Journal | Cell Host and Microbe |
| Volume | 22 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 12 Jul 2017 |
Keywords
- B cell lymphoma
- EBV
- Epstein-Barr virus
- humanized mouse model
- Kaposi sarcoma-associated herpesvirus
- KSHV
- lytic EBV replication
- primary effusion lymphoma
- virus-associated lymphoma
Cite this
}
Persistent KSHV Infection Increases EBV-Associated Tumor Formation In Vivo via Enhanced EBV Lytic Gene Expression. / McHugh, Donal; Caduff, Nicole; Barros, Mario Henrique M.; Rämer, Patrick C.; Raykova, Ana; Murer, Anita; Landtwing, Vanessa; Quast, Isaak; Styles, Christine T.; Spohn, Michael; Fowotade, Adeola; Delecluse, Henri Jacques; Papoudou-Bai, Alexandra; Lee, Yong Moon; Kim, Jin Man; Middeldorp, Jaap; Schulz, Thomas F.; Cesarman, Ethel; Zbinden, Andrea; Capaul, Riccarda; White, Robert E.; Allday, Martin J.; Niedobitek, Gerald; Blackbourn, David J.; Grundhoff, Adam; Münz, Christian.
In: Cell Host and Microbe, Vol. 22, No. 1, 12.07.2017, p. 61-73.e7.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - Persistent KSHV Infection Increases EBV-Associated Tumor Formation In Vivo via Enhanced EBV Lytic Gene Expression
AU - McHugh, Donal
AU - Caduff, Nicole
AU - Barros, Mario Henrique M.
AU - Rämer, Patrick C.
AU - Raykova, Ana
AU - Murer, Anita
AU - Landtwing, Vanessa
AU - Quast, Isaak
AU - Styles, Christine T.
AU - Spohn, Michael
AU - Fowotade, Adeola
AU - Delecluse, Henri Jacques
AU - Papoudou-Bai, Alexandra
AU - Lee, Yong Moon
AU - Kim, Jin Man
AU - Middeldorp, Jaap
AU - Schulz, Thomas F.
AU - Cesarman, Ethel
AU - Zbinden, Andrea
AU - Capaul, Riccarda
AU - White, Robert E.
AU - Allday, Martin J.
AU - Niedobitek, Gerald
AU - Blackbourn, David J.
AU - Grundhoff, Adam
AU - Münz, Christian
PY - 2017/7/12
Y1 - 2017/7/12
N2 - 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. McHugh et al. describe a small animal model of KSHV infection and demonstrate that KSHV collaborates with another human gamma herpes virus, EBV, to establish persistent infection in B cells. The emerging transformed cells resemble primary effusion lymphomas, the malignancies that frequently harbor both viruses in humans.
AB - 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. McHugh et al. describe a small animal model of KSHV infection and demonstrate that KSHV collaborates with another human gamma herpes virus, EBV, to establish persistent infection in B cells. The emerging transformed cells resemble primary effusion lymphomas, the malignancies that frequently harbor both viruses in humans.
KW - B cell lymphoma
KW - EBV
KW - Epstein-Barr virus
KW - humanized mouse model
KW - Kaposi sarcoma-associated herpesvirus
KW - KSHV
KW - lytic EBV replication
KW - primary effusion lymphoma
KW - virus-associated lymphoma
UR - http://www.scopus.com/inward/record.url?scp=85026903460&partnerID=8YFLogxK
U2 - 10.1016/j.chom.2017.06.009
DO - 10.1016/j.chom.2017.06.009
M3 - Article
VL - 22
SP - 61-73.e7
JO - Cell Host and Microbe
JF - Cell Host and Microbe
SN - 1931-3128
IS - 1
ER -