KSHV infection drives poorly cytotoxic CD56-negative natural killer cell differentiation in vivo upon KSHV/EBV dual infection
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Ong'echa, John M.
Oluoch, Peter O.
Schulz, Thomas F.
Blackbourn, David J.
Moormann, Ann M.
UMass Chan AffiliationsGraduate School of Biomedical Sciences
Division of Infectious Diseases, Department of Medicine
Document TypeJournal Article
KeywordsCD56-negative NK cells
Kaposi sarcoma-associated herpesvirus
humanized mouse model
natural killer cells
Hemic and Lymphatic Diseases
Immune System Diseases
Immunology of Infectious Disease
MetadataShow full item record
AbstractHerpesvirus infections shape the human natural killer (NK) cell compartment. While Epstein-Barr virus (EBV) expands immature NKG2A(+) NK cells, human cytomegalovirus (CMV) drives accumulation of adaptive NKG2C(+) NK cells. Kaposi sarcoma-associated herpesvirus (KSHV) is a close relative of EBV, and both are associated with lymphomas, including primary effusion lymphoma (PEL), which nearly always harbors both viruses. In this study, KSHV dual infection of mice with reconstituted human immune system components leads to the accumulation of CD56(-)CD16(+)CD38(+)CXCR6(+) NK cells. CD56(-)CD16(+) NK cells were also more frequently found in KSHV-seropositive Kenyan children. This NK cell subset is poorly cytotoxic against otherwise-NK-cell-susceptible and antibody-opsonized targets. Accordingly, NK cell depletion does not significantly alter KSHV infection in humanized mice. These data suggest that KSHV might escape NK-cell-mediated immune control by driving CD56(-)CD16(+) NK cell differentiation.
Caduff N, McHugh D, Rieble L, Forconi CS, Ong'echa JM, Oluoch PO, Raykova A, Murer A, Böni M, Zuppiger L, Schulz TF, Blackbourn DJ, Chijioke O, Moormann AM, Münz C. KSHV infection drives poorly cytotoxic CD56-negative natural killer cell differentiation in vivo upon KSHV/EBV dual infection. Cell Rep. 2021 May 4;35(5):109056. doi: 10.1016/j.celrep.2021.109056. PMID: 33951431. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/41912
RightsCopyright 2021 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Except where otherwise noted, this item's license is described as Copyright 2021 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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