Persistent KSHV Infection Increases EBV-Associated Tumor Formation In Vivo via Enhanced EBV Lytic Gene Expression

Donal McHugh; Nicole Caduff; Mario Henrique M Barros; Patrick C Rämer; Ana Raykova; Anita Murer; Vanessa Landtwing; Isaak Quast; Christine T Styles; Michael Spohn; Adeola Fowotade; Henri-Jacques Delecluse; Alexandra Papoudou-Bai; Yong-Moon Lee; Jin-Man Kim; Jaap Middeldorp; Thomas F Schulz; Ethel Cesarman; Andrea Zbinden; Riccarda Capaul; Robert E White; Martin J Allday; Gerald Niedobitek; David J Blackbourn; Adam Grundhoff; Christian Münz

doi:https://doi.org/10.1016/j.chom.2017.06.009

Persistent KSHV Infection Increases EBV-Associated Tumor Formation In Vivo via Enhanced EBV Lytic Gene Expression

Donal McHugh, Nicole Caduff, Mario Henrique M Barros, Patrick C Rämer, Ana Raykova, Anita Murer, Vanessa Landtwing, Isaak Quast, Christine T Styles, Michael Spohn, Adeola Fowotade, Henri-Jacques Delecluse, Alexandra Papoudou-Bai, Yong-Moon Lee, Jin-Man Kim, Jaap Middeldorp, Thomas F Schulz, Ethel Cesarman, Andrea Zbinden, Riccarda CapaulRobert E White, Martin J Allday, Gerald Niedobitek, David J Blackbourn, Adam Grundhoff, Christian Münz

Research output: Contribution to journal › Article › Academic › peer-review

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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.

Original language	English
Pages (from-to)	61-73.e7
Journal	CELL Host & Microbe
Volume	22
Issue number	1
DOIs	https://doi.org/10.1016/j.chom.2017.06.009
Publication status	Published - 12 Jul 2017

Keywords

Journal Article

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https://doi.org/10.1016/j.chom.2017.06.009

Cite this

McHugh, D., Caduff, N., Barros, M. H. M., Rämer, P. C., Raykova, A., Murer, A., Landtwing, V., Quast, I., Styles, C. T., Spohn, M., Fowotade, A., Delecluse, H.-J., Papoudou-Bai, A., Lee, Y.-M., Kim, J.-M., Middeldorp, J., Schulz, T. F., Cesarman, E., Zbinden, A., ... Münz, C. (2017). Persistent KSHV Infection Increases EBV-Associated Tumor Formation In Vivo via Enhanced EBV Lytic Gene Expression. CELL Host & Microbe, 22(1), 61-73.e7. https://doi.org/10.1016/j.chom.2017.06.009

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title = "Persistent KSHV Infection Increases EBV-Associated Tumor Formation In Vivo via Enhanced EBV Lytic Gene Expression",

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.",

keywords = "Journal Article",

author = "Donal McHugh and Nicole Caduff and Barros, {Mario Henrique M} and R{\"a}mer, {Patrick C} and Ana Raykova and Anita Murer and Vanessa Landtwing and Isaak Quast and Styles, {Christine T} and Michael Spohn and Adeola Fowotade and Henri-Jacques Delecluse and Alexandra Papoudou-Bai and Yong-Moon Lee and Jin-Man Kim and Jaap Middeldorp and Schulz, {Thomas F} and Ethel Cesarman and Andrea Zbinden and Riccarda Capaul and White, {Robert E} and Allday, {Martin J} and Gerald Niedobitek and Blackbourn, {David J} and Adam Grundhoff and Christian M{\"u}nz",

year = "2017",

month = jul,

day = "12",

doi = "https://doi.org/10.1016/j.chom.2017.06.009",

language = "English",

volume = "22",

pages = "61--73.e7",

journal = "CELL Host & Microbe",

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McHugh, D, Caduff, N, Barros, MHM, 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 2017, 'Persistent KSHV Infection Increases EBV-Associated Tumor Formation In Vivo via Enhanced EBV Lytic Gene Expression', CELL Host & Microbe, vol. 22, no. 1, pp. 61-73.e7. https://doi.org/10.1016/j.chom.2017.06.009

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.

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.

KW - Journal Article

U2 - https://doi.org/10.1016/j.chom.2017.06.009

DO - https://doi.org/10.1016/j.chom.2017.06.009

M3 - Article

C2 - 28704654

SN - 1931-3128

VL - 22

SP - 61-73.e7

JO - CELL Host & Microbe

JF - CELL Host & Microbe

IS - 1

ER -