Experimental infection of H5N1 HPAI in BALB/c mice
Vasily A Evseenko1, Eugeny K Bukin, Anna V Zaykovskaya
1State Research Center of Virology and Biotechnology Vector of Rospotrebnadzor, Koltsovo, Russia. vasily.evseenko@gmail.com
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.
Conclusion:
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.
Insights
Highly pathogenic avian influenza (H5N1 HPAI) became endemic in Russia. A novel Russian H5N1 HPAI strain, A/duck/Tuva/01/06, was characterized and validated as a suitable animal model for evaluating anti-influenza vaccines and therapeutics.
Area of Science:
- Virology
- Immunology
- Pathology
Background:
- Russia experienced a significant H5N1 highly pathogenic avian influenza (HPAI) epizooty in 2005, leading to endemicity.
- Subsequent outbreaks in 2006 necessitated the investigation of animal models for vaccine and antiviral therapy development.
- A highly pathogenic H5N1 HPAI strain was selected for these critical studies.
Purpose of the Study:
- To characterize a novel H5N1 HPAI strain isolated in Russia.
- To evaluate its suitability as an animal model for preclinical studies.
- To assess its pathogenicity and susceptibility to antiviral agents.
Main Methods:
- Molecular analysis to identify pathogenicity markers (cleavage site, PB2 K627).
- Pathogenicity testing including intravenous pathogenicity index (IVPI) and median lethal dose (MLD50).
- Antiviral sensitivity testing (adamantanes, neuraminidase inhibitors) and serological cross-reactivity analysis.
Main Results:
- The virus, A/duck/Tuva/01/06, belongs to the Quinghai-like group and is confirmed highly pathogenic (IVPI=3.0, MLD50=1.4Log10EID50).
- Molecular analysis indicated sensitivity to adamantanes and neuraminidase inhibitors.
- The model exhibited acute delayed hemorrhagic syndrome and hypercytokinemia (elevated IFN-gamma, IL-6, IL-10), with a mean time to death of 8.19 days.
Conclusions:
- The characterized virus, A/duck/Tuva/01/06, possesses key parameters making it a suitable model.
- This strain can be effectively utilized for evaluating the efficacy of anti-influenza vaccines and therapeutics.
