title: The pathogenicity of swan derived H5N1 virus in birds and mammals and its gene analysis.
abstract: BACKGROUND
  Highly pathogenic avian influenza (HPAI) H5N1 viruses continue to circulate in poultry and can infect and cause mortality in birds and mammals; the genetic determinants of their increased virulence are largely unknown. The main purpose of this work was to determine the correlation between known molecular determinants of virulence in different avian influenza virus (AIV) genes and the results of experimental infection of birds and mammals with AIV strain A/swan/Mangistau/3/06 (H5N1; SW/3/06).
  
  
  RESULTS
  We examined the virulence of SW/3/06 in four species of birds (chickens, ducks, turkeys, geese) and five species of mammals (mice, guinea pigs, cats, dogs, pigs), and identified the molecular determinants of virulence in 11 genes (HA, NA, PB1, PB1-F2, PB2, PA, NS1, NS2, M1, M2 and NP). SW/3/06 does not possess the prime virulence determinant of HPAIV - a polybasic HA cleavage site - and is highly pathogenic in chickens. SW/3/06 replicated efficiently in chickens, ducks, turkeys, mice and dogs, causing 100% mortality within 1.6-5.2 days. In addition, no mortalities were observed in geese, guinea pigs, cats and pigs. The HI assay demonstrated all not diseased animals infected with the SW/3/06 virus had undergone seroconversion by 14, 21 and 28 dpi. Eleven mutations in the seven genes were present in SW/3/06. These mutations may play a role in the pathogenicity of this strain in chickens, ducks, turkeys, mice and dogs. Together or separately, mutations 228S-103S-318I in HA may play a role in the efficient replication of SW/3/06 in mammals (mice, dogs, pigs).
  
  
  CONCLUSIONS
  This study provides new information on the pathogenicity of the newly-isolated swan derived H5N1 virus in birds and mammals, and explored the role of molecular determinants of virulence in different genes; such studies may help to identify key virulence or adaptation markers that can be used for global surveillance of viruses threatening to emerge into the human population.
authors.affiliation: The Research Institute for Biological Safety Problems, Zhambylskaya oblast, Kordayskiy rayon, Gvardeiskiy, 080409, Republic of Kazakhstan. tabynov777@mail.ru.
authors.forename: Kairat
authors.initials: K
authors.lastname: Tabynov
authors.affiliation: The Research Institute for Biological Safety Problems, Zhambylskaya oblast, Kordayskiy rayon, Gvardeiskiy, 080409, Republic of Kazakhstan. sansyzbai-ar@biosafety.kz.
authors.forename: Abylay
authors.initials: A
authors.lastname: Sansyzbay
authors.affiliation: The Research Institute for Biological Safety Problems, Zhambylskaya oblast, Kordayskiy rayon, Gvardeiskiy, 080409, Republic of Kazakhstan. snt@biosafety.kz.
authors.forename: Nurlan
authors.initials: N
authors.lastname: Sandybayev
authors.affiliation: The Research Institute for Biological Safety Problems, Zhambylskaya oblast, Kordayskiy rayon, Gvardeiskiy, 080409, Republic of Kazakhstan. murat@biosafety.kz.
authors.forename: Muratbay
authors.initials: M
authors.lastname: Mambetaliyev
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics* / Q000302:isolation & purification / Q000472:pathogenicity*; D008297:Male; D008322:Mammals; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000473:pathology* / Q000821:virology*; D011200:Poultry; D016019:Survival Analysis; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics*
chemical_list: D037521:Virulence Factors