Thumbnail Image
Publication

Kaposi's sarcoma-associated herpesvirus vIRF2 protein utilizes an IFN-dependent pathway to regulate viral early gene expression.

Koch, Sandra
; 
Damas, Modester
; 
Freise, Anika
; 
Hage, Elias
; 
Dhingra, Akshay
; 
Rückert, Jessica
; 
Gallo, Antonio
; 
Kremmer, Elisabeth
; ; ... show 2 more
Citations
Altmetric:
Advisors
Editors
Other Contributors
Issue Date
2019-05-01
Submitted date
Show all metadata
Files
Thumbnail Image
Open Access publication
Adobe PDF, 3.22 MB
Other Titles
Abstract
Kaposi's sarcoma-associated herpesvirus (KSHV; human herpesvirus 8) belongs to the subfamily of Gammaherpesvirinae and is the etiological agent of Kaposi's sarcoma as well as of two lymphoproliferative diseases: primary effusion lymphoma and multicentric Castleman disease. The KSHV life cycle is divided into a latent and a lytic phase and is highly regulated by viral immunomodulatory proteins which control the host antiviral immune response. Among them is a group of proteins with homology to cellular interferon regulatory factors, the viral interferon regulatory factors 1-4. The KSHV vIRFs are known as inhibitors of cellular interferon signaling and are involved in different oncogenic pathways. Here we characterized the role of the second vIRF protein, vIRF2, during the KSHV life cycle. We found the vIRF2 protein to be expressed in different KSHV positive cells with early lytic kinetics. Importantly, we observed that vIRF2 suppresses the expression of viral early lytic genes in both newly infected and reactivated persistently infected endothelial cells. This vIRF2-dependent regulation of the KSHV life cycle might involve the increased expression of cellular interferon-induced genes such as the IFIT proteins 1, 2 and 3, which antagonize the expression of early KSHV lytic proteins. Our findings suggest a model in which the viral protein vIRF2 allows KSHV to harness an IFN-dependent pathway to regulate KSHV early gene expression.
Citation
PLoS Pathog. 2019 May 6;15(5):e1007743. doi: 10.1371/journal.ppat.1007743. eCollection 2019 May.
Affiliation
HZI, Helmholtz Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany.
Publisher
PLOS
Journal
PLOS Pathogens
URI
http://hdl.handle.net/10033/621790
DOI
10.1371/journal.ppat.1007743
PubMed ID
31059555
PubMed Central ID
Additional Links
Embedded video
Type
Article
Language
en
Description
Series/Report no.
ISSN
1553-7374
EISSN
ISBN
ISMN
Gov't Doc #
Sponsors
License
Attribution-NonCommercial-ShareAlike 4.0 International
cbn
Collections
Publications of the research group Chemical Biology (CBIO)