title: Gamma interferon controls mouse polyomavirus infection in vivo.
abstract: Human polyomaviruses are associated with substantial morbidity in immunocompromised patients, including those with HIV/AIDS, recipients of bone marrow and kidney transplants, and individuals receiving immunomodulatory agents for autoimmune and inflammatory diseases. No effective antipolyomavirus agents are currently available, and no host determinants have been identified to predict susceptibility to polyomavirus-associated diseases. Using the mouse polyomavirus (MPyV) infection model, we recently demonstrated that perforin-granzyme exocytosis, tumor necrosis factor alpha (TNF-α), and Fas did not contribute to control of infection or virus-induced tumors. Gamma interferon (IFN-γ) was recently shown to inhibit replication by human BK polyomavirus in primary cultures of renal tubular epithelial cells. In this study, we provide evidence that IFN-γ is an important component of the host defense against MPyV infection and tumorigenesis. In immortalized and primary cells, IFN-γ reduces expression of MPyV proteins and impairs viral replication. Mice deficient for the IFN-γ receptor (IFN-γR(-/-)) maintain higher viral loads during MPyV infection and are susceptible to MPyV-induced tumors; this increased viral load is not associated with a defective MPyV-specific CD8(+) T cell response. Using an acute MPyV infection kidney transplant model, we further show that IFN-γR(-/-) donor kidneys harbor higher MPyV levels than donor kidneys from wild-type mice. Finally, administration of IFN-γ to persistently infected mice significantly reduces MPyV levels in multiple organs, including the kidney, a major reservoir for persistent mouse and human polyomavirus infections. These findings demonstrate that IFN-γ is an antiviral effector molecule for MPyV infection.
authors.affiliation: Department of Pathology, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Jarad J
authors.initials: JJ
authors.lastname: Wilson
authors.forename: Eugene
authors.initials: E
authors.lastname: Lin
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Pack
authors.forename: Elizabeth L
authors.initials: EL
authors.lastname: Frost
authors.forename: Annette
authors.initials: A
authors.lastname: Hadley
authors.forename: Alyson I
authors.initials: AI
authors.lastname: Swimm
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Ying
authors.initials: Y
authors.lastname: Dong
authors.forename: Cynthia P
authors.initials: CP
authors.lastname: Breeden
authors.forename: Daniel
authors.initials: D
authors.lastname: Kalman
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Newell
authors.forename: Aron E
authors.initials: AE
authors.lastname: Lukacher
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D007371:Interferon-gamma / Q000008:administration & dosage / Q000276:immunology*; D007668:Kidney / Q000276:immunology / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011120:Polyomavirus / Q000276:immunology* / Q000472:pathogenicity*; D027601:Polyomavirus Infections / Q000276:immunology* / Q000473:pathology*; D012376:Rodent Diseases / Q000276:immunology / Q000473:pathology / Q000821:virology; D019562:Viral Load; D014764:Viral Proteins / Q000037:antagonists & inhibitors; D014779:Virus Replication / Q000187:drug effects
chemical_list: D014764:Viral Proteins; D007371:Interferon-gamma