TY - JOUR
T1 - The Epstein-Barr Virus Oncogene EBNA1 Suppresses Natural Killer Cell Responses and Apoptosis Early after Infection of Peripheral B Cells
AU - Smith, Danielle Westhoff
AU - Chakravorty, Adityarup
AU - Hayes, Mitch
AU - Hammerschmidt, Wolfgang
AU - Sugden, Bill
N1 - Publisher Copyright:
© 2021 American Society for Microbiology. All rights reserved.
PY - 2021/12/1
Y1 - 2021/12/1
N2 - The innate immune system serves as frontline defense against pathogens, such as bacteria and viruses. Natural killer (NK) cells are a part of innate immunity and can both secrete cytokines and directly target cells for lysis. NK cells express several cell surface receptors, including NKG2D, which bind multiple ligands. People with deficiencies in NK cells are often susceptible to uncontrolled infection by herpesviruses, such as Epstein-Barr virus (EBV). Infection with EBV stimulates both innate and adaptive immunity, yet the virus establishes lifelong latent infection in memory B cells. We show that the EBV oncogene EBNA1, previously known to be necessary for maintaining EBV genomes in latently infected cells, also plays an important role in suppressing NK cell responses and cell death in newly infected cells. EBNA1 does so by downregulating the NKG2D ligands ULBP1 and ULBP5 and modulating expression of c-Myc. B cells infected with a derivative of EBV that lacks EBNA1 are more susceptible to NK cell-mediated killing and show increased levels of apoptosis. Thus, EBNA1 performs a previously unappreciated role in reducing immune response and programmed cell death after EBV infection, helping infected cells avoid immune surveillance and apoptosis and thus persist for the lifetime of the host.
AB - The innate immune system serves as frontline defense against pathogens, such as bacteria and viruses. Natural killer (NK) cells are a part of innate immunity and can both secrete cytokines and directly target cells for lysis. NK cells express several cell surface receptors, including NKG2D, which bind multiple ligands. People with deficiencies in NK cells are often susceptible to uncontrolled infection by herpesviruses, such as Epstein-Barr virus (EBV). Infection with EBV stimulates both innate and adaptive immunity, yet the virus establishes lifelong latent infection in memory B cells. We show that the EBV oncogene EBNA1, previously known to be necessary for maintaining EBV genomes in latently infected cells, also plays an important role in suppressing NK cell responses and cell death in newly infected cells. EBNA1 does so by downregulating the NKG2D ligands ULBP1 and ULBP5 and modulating expression of c-Myc. B cells infected with a derivative of EBV that lacks EBNA1 are more susceptible to NK cell-mediated killing and show increased levels of apoptosis. Thus, EBNA1 performs a previously unappreciated role in reducing immune response and programmed cell death after EBV infection, helping infected cells avoid immune surveillance and apoptosis and thus persist for the lifetime of the host.
KW - B cell
KW - C-Myc
KW - Epstein-Barr virus
KW - Herpesviruses
KW - Innate immunity
KW - Natural killer cells
KW - ULBP
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UR - http://www.scopus.com/inward/citedby.url?scp=85121922767&partnerID=8YFLogxK
U2 - 10.1128/mBio.02243-21
DO - 10.1128/mBio.02243-21
M3 - Article
C2 - 34781735
AN - SCOPUS:85121922767
SN - 2161-2129
VL - 12
JO - mBio
JF - mBio
IS - 6
M1 - e02243-21
ER -