title: Humanized Mice Reproduce Acute and Persistent Human Adenovirus Infection.
abstract: Severe human adenovirus (HAdV) infections are an increasing threat for immunosuppressed individuals, particularly those who have received stem cell transplants. It has been previously hypothesized that severe infections might be due to reactivation of a persistent infection, but this hypothesis has been difficult to test owing to the lack of a permissive in vivo model of HAdV infection. Here we established a humanized mouse model that reproduces features of acute and persistent HAdV infection. In this model, acute infection correlated with high mortality, weight loss, liver pathology, and expression of viral proteins in several organs. In contrast, persistent infection was asymptomatic and led to establishment of HAdV-specific adaptive immunity and expression of early viral genes exclusively in the bone marrow. These findings validate the use of humanized mice to study acute and persistent HAdV infection and strongly suggest the presence of cellular reservoirs in the bone marrow.
authors.affiliation: Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg.|German Center for Infection Research, Braunschweig, (DZIF), Partner Site Hamburg, Germany.
authors.forename: Estefanía
authors.initials: E
authors.lastname: Rodríguez
authors.affiliation: Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg.|German Center for Infection Research, Braunschweig, (DZIF), Partner Site Hamburg, Germany.
authors.forename: Wing Hang
authors.initials: WH
authors.lastname: Ip
authors.affiliation: Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg.|German Center for Infection Research, Braunschweig, (DZIF), Partner Site Hamburg, Germany.
authors.forename: Viktoria
authors.initials: V
authors.lastname: Kolbe
authors.affiliation: Institute for Neuropathology, University Medical Center Hamburg-Eppendorf.
authors.forename: Kristin
authors.initials: K
authors.lastname: Hartmann
authors.affiliation: Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg.|German Center for Infection Research, Braunschweig, (DZIF), Partner Site Hamburg, Germany.
authors.forename: Gundula
authors.initials: G
authors.lastname: Pilnitz-Stolze
authors.affiliation: Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg.|German Center for Infection Research, Braunschweig, (DZIF), Partner Site Hamburg, Germany.
authors.forename: Nilgün
authors.initials: N
authors.lastname: Tekin
authors.affiliation: Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg.|German Center for Infection Research, Braunschweig, (DZIF), Partner Site Hamburg, Germany.
authors.forename: Sergio
authors.initials: S
authors.lastname: Gómez-Medina
authors.affiliation: Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg.|German Center for Infection Research, Braunschweig, (DZIF), Partner Site Hamburg, Germany.
authors.forename: César
authors.initials: C
authors.lastname: Muñoz-Fontela
authors.affiliation: Institute for Neuropathology, University Medical Center Hamburg-Eppendorf.
authors.forename: Susanne
authors.initials: S
authors.lastname: Krasemann
authors.affiliation: Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg.|German Center for Infection Research, Braunschweig, (DZIF), Partner Site Hamburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Dobner
mesh_terms: D000208:Acute Disease; D056704:Adaptive Immunity; D000258:Adenovirus Infections, Human / Q000276:immunology / Q000821:virology*; D000260:Adenoviruses, Human / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D000818:Animals; D058345:Asymptomatic Infections; D001853:Bone Marrow / Q000821:virology; D004279:DNA, Viral / Q000235:genetics; D004195:Disease Models, Animal; D006801:Humans; D016867:Immunocompromised Host; D008099:Liver / Q000473:pathology / Q000821:virology; D051379:Mice; D008822:Mice, Transgenic; D019562:Viral Load; D014766:Viremia
chemical_list: D004279:DNA, Viral
keywords: adenovirus; antiviral therapy; bone marrow; humanized mice; persistent infection; stem cell transplant; viral hepatitis