Until 2005 avian influenza was regional problem of sev- [4] and question "why had only some wild waterfowl died?" is still unclear. Most of the outbreaks in Russia associated with wild birds. The same time viruses adapted to wild birds are extremely pathogenic for poultry and mice. This "competitive advantage" makes Quinghailike viruses most probable candidate to be precursor for new pandemic influenza virus. At the same time pathogenesis of different (phylogenetical clades) HPAI reveal common causes. The principal causes of rapid mice death after infecting with HPAI are primary viral pneumonia, ARDS, lesions of central nervous system and multiple organ failure. Our data suggest that A/duck/Tuva/01/06 strain of HPAI caused lethal pneumonia and spread systemically to the brain in BALB/c mice. Lesion of respiratory epithelium and following an activation of monocytes/macrophages results in a release of proinflammatory cytokines (TNF-α, IL-6) which are a hallmark of ARDS in murine model [27] . Despite powerful anti-influenza virus effects of TNF-α in lung tissue, as it was described previously [28] , we consider that elevated production of the cytokines seems to be crucial in the pathogenesis of HPAI infection. Moreover, it was shown that lethal H5N1 viruses are resistant to antiviral effects of interferons and TNF-α [29] . Virus-induced overexpression of TNF-α as well as high IFN-γ lead to activation of endothelium and imbalance in blood coagulation system [30] . This may explain the hemorrhagic syndrome as observed in some of animals. To pay attention that IL-12 is a potent inducer of IFN-γ synthesis by blood mononuclear cells [31] , we concluded the same cytokines hyperproduction reflects macrophage overactivation and subsequent hypercytokinemia. This cascade of events Phylogenetic tree based on full length sequencesof HA Figure 2 Phylogenetic tree based on full length sequencesof HA. Nucleotide sequences were analyzed by using the neighborjoining method with 500 bootstraps. The phylogenetic tree was rooted to the HA gene of A/goose/Guangdong/1/96 (H5N1) virus.