Experimental infection of H5N1 HPAI in BALB/c mice.
BACKGROUND
In 2005 huge epizooty of H5N1 HPAI occurred in Russia. It had been clear that territory of Russia becoming endemic for H5N1 HPAI. In 2006 several outbreaks have occurred. To develop new vaccines and antiviral therapies, animal models had to be investigated. We choose highly pathogenic strain for these studies.


RESULTS
A/duck/Tuva/01/06 belongs to Quinghai-like group viruses. Molecular markers-cleavage site, K627 in PB2 characterize this virus as highly pathogenic. This data was confirmed by direct pathogenic tests: IVPI = 3.0, MLD50 = 1,4Log10EID50. Also molecular analysis showed sensitivity of the virus to adamantanes and neuraminidase inhibitors. Serological analysis showed wide cross-reactivity of this virus with sera produced to H5N1 HPAI viruses isolated earlier in South-East Asia. Mean time to death of infected animals was 8,19+/-0,18 days. First time acute delayed hemorrhagic syndrome was observed in mice lethal model. Hypercytokinemia was determined by elevated sera levels of IFN-gamma, IL-6, IL-10.


CONCLUSIONS
Assuming all obtained data we can conclude that basic model parameters were characterized and virus A/duck/Tuva/01/06 can be used to evaluate anti-influenza vaccines and therapeutics.
Evseenko
Vasily A
VA
State Research Center of Virology and Biotechnology Vector of Rospotrebnadzor, Koltsovo, Russia. vasily.evseenko@gmail.com
Bukin
Eugeny K
EK
Zaykovskaya
Anna V
AV
Sharshov
Kirill A
KA
Ternovoi
Vladimir A
VA
Ignatyev
George M
GM
Shestopalov
Alexander M
AM
D000547:Amantadine / Q000494:pharmacology; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D000998:Antiviral Agents / Q000494:pharmacology; D015415:Biomarkers / Q000378:metabolism; D002642:Chick Embryo; D003429:Cross Reactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006470:Hemorrhage / Q000473:pathology; D053124:Influenza A Virus, H5N1 Subtype / Q000737:chemistry / Q000187:drug effects / Q000276:immunology / Q000472:pathogenicity*; D007371:Interferon-gamma / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D007422:Intestines / Q000473:pathology; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D009439:Neuraminidase / Q000037:antagonists & inhibitors; D009976:Orthomyxoviridae Infections / Q000097:blood* / Q000473:pathology*; D012867:Skin / Q000473:pathology; D014764:Viral Proteins / Q000378:metabolism; D014774:Virulence
D000914:Antibodies, Viral; D000998:Antiviral Agents; D015415:Biomarkers; D004791:Enzyme Inhibitors; D015850:Interleukin-6; C502893:PB2 protein, influenza virus; D014764:Viral Proteins; D016753:Interleukin-10; D007371:Interferon-gamma; D000547:Amantadine; D009439:Neuraminidase