title: Murine cytomegalovirus (CMV) infection via the intranasal route offers a robust model of immunity upon mucosal CMV infection.
abstract: Cytomegalovirus (CMV) is a ubiquitous virus, causing the most common congenital infection in humans, yet a vaccine against this virus is not available. Experimental studies of immunity against CMV in animal models of infection, such as the infection of mice with mouse CMV (MCMV), have relied mainly on parenteral infection protocols, although the virus naturally transmits by mucosal routes via body fluids. To characterize the biology of infections by mucosal routes, we compared the kinetics of virus replication, latent viral load and CD8 T-cell responses in lymphoid organs upon experimental intranasal (targeting the respiratory tract) and intragastric (targeting the digestive tract) infection with systemic intraperitoneal infection of two unrelated mouse strains. We observed that intranasal infection induced robust and long-term virus replication in the lungs and salivary glands but limited replication in the spleen. CD8 T-cell responses were somewhat weaker than upon intraperitoneal infection but showed similar kinetic profiles and phenotypes of antigen-specific cells. In contrast, intragastric infection resulted in abortive or poor virus replication in all tested organs and poor T-cell responses to the virus, especially at late times after infection. Consistent with the T-cell kinetics, the MCMV latent load was high in the lungs but low in the spleen of intranasally infected mice and lowest in all tested organs upon intragastric infection. In conclusion, we showed that intranasal but not intragastric infection of mice with MCMV represents a robust model to study the short- and long-term biology of CMV infection by a mucosal route.
authors.affiliation: Department of Vaccinology/Immune Aging and Chronic Infections, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Jennifer D
authors.initials: JD
authors.lastname: Oduro
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Anke
authors.initials: A
authors.lastname: Redeker
authors.affiliation: Institute for Virology and Research Center for Immunotherapy (FZI), University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.
authors.forename: Niels A W
authors.initials: NAW
authors.lastname: Lemmermann
authors.affiliation: Department of Vaccinology/Immune Aging and Chronic Infections, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Linda
authors.initials: L
authors.lastname: Ebermann
authors.affiliation: Department of Vaccinology/Immune Aging and Chronic Infections, Helmholtz Centre for Infection Research, Braunschweig, Germany.|Dar es Salaam University College of Education, Tanzania.
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Marandu
authors.affiliation: Department of Vaccinology/Immune Aging and Chronic Infections, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Iryna
authors.initials: I
authors.lastname: Dekhtiarenko
authors.affiliation: Department of Vaccinology/Immune Aging and Chronic Infections, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Julia K
authors.initials: JK
authors.lastname: Holzki
authors.affiliation: Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München, Munich, Germany.|Focus Group 'Clinical Cell Processing and Purification', Institute for Advanced Study, Technische Universität München, Munich, Germany.|German Center for Infection Research (DZIF), Braunschweig, Germany.
authors.forename: Dirk H
authors.initials: DH
authors.lastname: Busch
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Ramon
authors.initials: R
authors.lastname: Arens
authors.affiliation: German Center for Infection Research (DZIF), Braunschweig, Germany.|Department of Vaccinology/Immune Aging and Chronic Infections, Helmholtz Centre for Infection Research, Braunschweig, Germany.|Department for Virology, Medical School Hannover, Hannover, Germany.
authors.forename: Luka
authors.initials: L
authors.lastname: Čičin-Šain
mesh_terms: D000825:Animal Structures / Q000821:virology; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D018928:Immunity, Mucosal; D057507:Mice, 129 Strain; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D018146:Muromegalovirus / Q000276:immunology* / Q000502:physiology*; D019562:Viral Load; D017735:Virus Latency; D014779:Virus Replication