title: Genetic labeling reveals altered turnover and stability of innate lymphocytes in latent mouse cytomegalovirus infection.
abstract: Mouse CMV (MCMV) infection rapidly induces the proliferation of NK cells, which correlates with immunological protection. Whether NK cells primed during acute response against MCMV are maintained for the long term is not known. In this study, we used TcrdH2BeGFP mice in which maturing NK cells are genetically labeled with a pulse of very stable histone-2B-eGFP. In this system, we found that the reporter protein was diluted out upon NK cell division during acute MCMV infection. At the same time, mature NK cells in uninfected mice showed only very limited turnover in vivo. Three months after primary infection when MCMV latency was established, the majority of peripheral NK cells still displayed a higher record of proliferation than NK cells in mock-infected controls. This observation included both Ly49H(+) and Ly49H(-) NK cells. Conversely, naive NK cells did not show more proliferation after transfer into latently MCMV-infected mice than that after transfer into mock-infected control mice. This indicated that the observed alterations of the NK cell compartment in MCMV latency were "legacy" (i.e., resulting from prior events during the initial immune response). Together, these results suggest that antiviral immune responses induce sustained alterations of innate lymphocyte populations that extend far beyond the first days of acute infection.
authors.affiliation: Hannover Medical School, Institute for Virology, 30625 Hannover, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Busche
authors.forename: Susanne
authors.initials: S
authors.lastname: Schmitz
authors.forename: Henrike
authors.initials: H
authors.lastname: Fleige
authors.forename: Scott H
authors.initials: SH
authors.lastname: Robbins
authors.forename: Thierry
authors.initials: T
authors.lastname: Walzer
authors.forename: Charles A
authors.initials: CA
authors.lastname: Stewart
authors.forename: Reinhold
authors.initials: R
authors.lastname: Förster
authors.forename: Martin
authors.initials: M
authors.lastname: Messerle
authors.forename: Immo
authors.initials: I
authors.lastname: Prinz
mesh_terms: D000208:Acute Disease; D000818:Animals; D003586:Cytomegalovirus Infections / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D049452:Green Fluorescent Proteins / Q000235:genetics; D006657:Histones / Q000235:genetics; D007113:Immunity, Innate / Q000235:genetics*; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018146:Muromegalovirus / Q000235:genetics / Q000276:immunology; D055650:NK Cell Lectin-Like Receptor Subfamily A / Q000096:biosynthesis / Q000172:deficiency / Q000502:physiology; D017735:Virus Latency / Q000235:genetics / Q000276:immunology*
chemical_list: D006657:Histones; D055650:NK Cell Lectin-Like Receptor Subfamily A; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins