title: Systemic virus distribution and host responses in brain and intestine of chickens infected with low pathogenic or high pathogenic avian influenza virus.
abstract: BACKGROUND
  Avian influenza virus (AIV) is classified into two pathotypes, low pathogenic (LP) and high pathogenic (HP), based on virulence in chickens.Differences in pathogenicity between HPAIV and LPAIV might eventually be related to specific characteristics of strains, tissue tropism and host responses.
  
  
  METHODS
  To study differences in disease development between HPAIV and LPAIV, we examined the first appearance and eventual load of viral RNA in multiple organs as well as host responses in brain and intestine of chickens infected with two closely related H7N1 HPAIV or LPAIV strains.
  
  
  RESULTS
  Both H7N1 HPAIV and LPAIV spread systemically in chickens after a combined intranasal/intratracheal inoculation. In brain, large differences in viral RNA load and host gene expression were found between H7N1 HPAIV and LPAIV infected chickens. Chicken embryo brain cell culture studies revealed that both HPAIV and LPAIV could infect cultivated embryonic brain cells, but in accordance with the absence of the necessary proteases, replication of LPAIV was limited. Furthermore, TUNEL assay indicated apoptosis in brain of HPAIV infected chickens only. In intestine, where endoproteases that cleave HA of LPAIV are available, we found minimal differences in the amount of viral RNA and a large overlap in the transcriptional responses between HPAIV and LPAIV infected chickens. Interestingly, brain and ileum differed clearly in the cellular pathways that were regulated upon an AI infection.
  
  
  CONCLUSIONS
  Although both H7N1 HPAIV and LPAIV RNA was detected in a broad range of tissues beyond the respiratory and gastrointestinal tract, our observations indicate that differences in pathogenicity and mortality between HPAIV and LPAIV could originate from differences in virus replication and the resulting host responses in vital organs like the brain.
authors.affiliation: Central Veterinary Institute of Wageningen UR. P.O. Box 65, 8200 AB Lelystad, The Netherlands. jacob.post@wur.nl
authors.forename: Jacob
authors.initials: J
authors.lastname: Post
authors.forename: Dave W
authors.initials: DW
authors.lastname: Burt
authors.forename: Jan B W J
authors.initials: JB
authors.lastname: Cornelissen
authors.forename: Venice
authors.initials: V
authors.lastname: Broks
authors.forename: Diana
authors.initials: D
authors.lastname: van Zoelen
authors.forename: Ben
authors.initials: B
authors.lastname: Peeters
authors.forename: Johanna M J
authors.initials: JM
authors.lastname: Rebel
mesh_terms: D000818:Animals; D017209:Apoptosis; D001921:Brain / Q000378:metabolism / Q000821:virology; D002642:Chick Embryo; D002645:Chickens / Q000821:virology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D057916:Influenza A Virus, H7N1 Subtype / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity*; D005585:Influenza in Birds / Q000235:genetics / Q000821:virology*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000821:virology; D008297:Male; D012367:RNA, Viral / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D012367:RNA, Viral