title: Cardioselective infection with coxsackievirus B3 requires intact type I interferon signaling: implications for mortality and early viral replication.
abstract: BACKGROUND
  Interferons (IFNs) play an important role in antiviral defense and have therapeutic potential in coxsackievirus heart disease. However, little is known about the relative contributions of type I and type II IFN signaling in coxsackievirus B3 (CVB3) infection or their role in the cardioselective nature of CVB3 infection.
  
  
  RESULTS
  Wild-type mice and mice deficient for either the type I or the type II IFN receptor (IFNR) were infected with CVB3. Infection of the type I IFNR-deficient mice with >10(3) plaque-forming units (pfu) of CVB3 resulted in 100% mortality within 2 to 4 days after infection. Death was rare in wild-type and type II IFNR-deficient mice after inoculation with as much as 10(8) pfu of CVB3. Surprisingly, the early mortality in the type I IFNR-deficient mice was not accompanied by higher virus titers in the heart. Unexpectedly, a dramatic increase of viral RNA in the liver was found to correlate with early mortality in type I IFNR-deficient mice.
  
  
  CONCLUSIONS
  Type I but not type II IFN signaling is essential for the prevention of early death due to CVB3 infection. Interestingly, neither type I or type II IFN signaling has a dramatic effect on early viral replication in the heart. However, lethal viral replication in the liver is controlled by type I IFNs. These results demonstrate that the IFN system is capable of modulating both viral pathogenicity and tissue tropism.
authors.affiliation: Deutsches Herzzentrum and 1 Medizinische Klinik, Technische Universität, Munich, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Wessely
authors.forename: K
authors.initials: K
authors.lastname: Klingel
authors.forename: K U
authors.initials: KU
authors.lastname: Knowlton
authors.forename: R
authors.initials: R
authors.lastname: Kandolf
mesh_terms: D000818:Animals; D003384:Coxsackievirus Infections / Q000517:prevention & control / Q000821:virology*; D004195:Disease Models, Animal; D029822:Enterovirus B, Human / Q000187:drug effects / Q000472:pathogenicity* / Q000502:physiology; D006321:Heart / Q000821:virology; D007370:Interferon Type I / Q000235:genetics / Q000502:physiology* / Q000627:therapeutic use; D007371:Interferon-gamma / Q000502:physiology / Q000627:therapeutic use; D008099:Liver / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D012367:RNA, Viral / Q000378:metabolism; D015398:Signal Transduction; D014779:Virus Replication / Q000187:drug effects
chemical_list: D007370:Interferon Type I; D012367:RNA, Viral; D007371:Interferon-gamma