title: Acute murine H5N1 influenza A encephalitis.
abstract: Avian influenza A virus H5N1 has the proven capacity to infect humans through cross-species transmission, but to date, efficient human-to-human transmission is limited. In natural avian hosts, animal models and sporadic human outbreaks, H5N1 infection has been associated with neurological disease. We infected BALB/c mice intranasally with H5N1 influenza A/Viet Nam/1203/2004 to study the immune response during acute encephalitis. Using immunohistochemistry and in situ hybridization, we compared the time course of viral infection with activation of immunity. By 5 days postinfection (DPI), mice had lost substantial body weight and required sacrifice by 7 DPI. H5N1 influenza was detected in the lung as early as 1 DPI, whereas infected neurons were not observed until 4 DPI. H5N1 infection of BALB/c mice developed into severe acute panencephalitis. Infected neurons lacked evidence of a perineuronal net and exhibited signs of apoptosis. Whereas lung influenza infection was associated with an early type I interferon (IFN) response followed by a reduction in viral burden concordant with appearance of IFN-γ, the central nervous system environment exhibited a blunted type I IFN response.
authors.affiliation: Division of Neuropathology, Department of Pathology Graduate Program in Immunology Department of Microbiology and Molecular Genetics Center for Vaccine Research, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA. sjb75@pitt.edu
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Bissel
authors.forename: Brendan M
authors.initials: BM
authors.lastname: Giles
authors.forename: Guoji
authors.initials: G
authors.lastname: Wang
authors.forename: Dane C
authors.initials: DC
authors.lastname: Olevian
authors.forename: Ted M
authors.initials: TM
authors.lastname: Ross
authors.forename: Clayton A
authors.initials: CA
authors.lastname: Wiley
mesh_terms: D000208:Acute Disease; D000818:Animals; D004195:Disease Models, Animal; D018792:Encephalitis, Viral / Q000473:pathology* / Q000821:virology*; D005260:Female; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000472:pathogenicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000473:pathology* / Q000821:virology*; D011024:Pneumonia, Viral / Q000473:pathology / Q000821:virology