Division of Infectious Diseases, Department of Medicine; Graduate School of Biomedical Sciences
Hemic and Lymphatic Diseases | Immune System Diseases | Immunology of Infectious Disease | Immunopathology | Infectious Disease | Virus Diseases | Viruses
Herpesvirus 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.
CD56-negative NK cells, EBV, Epstein-Barr virus, KSHV, Kaposi sarcoma-associated herpesvirus, humanized mouse model, natural killer cells
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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/).
DOI of Published Version
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
Caduff N, McHugh D, Rieble L, Forconi C, Ong'echa JM, Oluoch PO, Raykova A, Murer A, Boni M, Zuppiger L, Schulz TF, Blackbourn DJ, Chijioke O, Moormann AM, Munz C. (2021). KSHV infection drives poorly cytotoxic CD56-negative natural killer cell differentiation in vivo upon KSHV/EBV dual infection. Open Access Publications by UMass Chan Authors. https://doi.org/10.1016/j.celrep.2021.109056. Retrieved from https://escholarship.umassmed.edu/oapubs/4719
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