KSHV infection drives poorly cytotoxic CD56-negative natural killer cell differentiation in vivo upon KSHV/EBV dual infection
Nicole Caduff,
Donal McHugh,
Lisa Rieble,
Catherine S. Forconi,
John M. Ong’echa,
Peter O. Oluoch,
Ana Raykova,
Anita Murer,
Michelle Böni,
Lara Zuppiger,
Thomas F. Schulz,
David J. Blackbourn,
Obinna Chijioke,
Ann M. Moormann,
Christian Münz
Affiliations
Nicole Caduff
Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, Zürich, Switzerland
Donal McHugh
Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, Zürich, Switzerland
Lisa Rieble
Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, Zürich, Switzerland
Catherine S. Forconi
Division of Infectious Diseases, Department of Medicine, University of Massachusetts Medical School, Worcester, MA, USA
John M. Ong’echa
Center for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya
Peter O. Oluoch
Division of Infectious Diseases, Department of Medicine, University of Massachusetts Medical School, Worcester, MA, USA; Center for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya
Ana Raykova
Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, Zürich, Switzerland
Anita Murer
Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, Zürich, Switzerland
Michelle Böni
Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, Zürich, Switzerland
Lara Zuppiger
Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, Zürich, Switzerland
Thomas F. Schulz
Institute of Virology, Hannover Medical School, Hannover and German Centre of Infection Research (DZIF), Hannover-Braunschweig Site, Hannover, Germany
David J. Blackbourn
School of Biosciences and Medicine, University of Surrey, Guildford, UK
Obinna Chijioke
Cellular Immunotherapy, Institute of Experimental Immunology, University of Zürich, Zürich, Switzerland
Ann M. Moormann
Division of Infectious Diseases, Department of Medicine, University of Massachusetts Medical School, Worcester, MA, USA
Christian Münz
Viral Immunobiology, Institute of Experimental Immunology, University of Zürich, Zürich, Switzerland; Corresponding author
Summary: 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.
