Experimental infection of H5N1 HPAI in BALB/c mice

Abstract

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.

Detection of expression of influenza virus receptors in tissues of BALB/c mice by histochemistry

“…These data agree with previous reports in this and other species (Matrosovich et al 2004;Thompson et al 2006;Ibricevic et al 2006;Shinya et al 2006). This may explain why air tract infection was successfully achieved in BALB/c mice (Evseenko et al 2007;Vigerust et al 2007;Gillim-Ross et al 2008;Wolk et al 2008;Xu et al 2006). Although viral recognition of cell surface sialic acid linkages is not the only determinant of infectivity, this finding led to the hypothesis that the absence of both receptors on the superficial epithelium of nasal mucosa and abundance of expression in the lower respiratory tract may account for the observed pathological changes with infection.…”

“…It was also in agreement with the data obtained with infection of epithelial cells as suggested in a previous study on tissue tropism in human (Gu et al 2007). The presence of alpha-2,3 sialic acid-linked receptors on endothelial cells in the cecum and rectum may be of interest, as infection of such cells could explain the gastrointestinal symptoms often observed in H5N1 cases (Bright et al 2003;Li et al 2008;Guo et al 2000;Evseenko et al 2007;Lipatov et al 2005).…”

“…Spleen, liver and kidney express both receptors, which is an explanation for the severe pathological changes observed in this organ when influenza virus infection occurred (Bright et al 2003;Li et al 2008;Guo et al 2000;Evseenko et al 2007;Liu et al 2005;Maines et al 2005). It is interesting note that the heart expresses alpha-2,3 sialic acid-linked receptors not alpha-2,6 sialic acid-linked receptors, but both HuIV and AIV infection can cause pathological change in the hearts of mice (Kotaka et al 1990;Kitaura et al 2003;Kishimoto et al 2005), this need to be exploited.…”

The Induction of Proinflammatory Cytokines in Response to Avian Influenza H5N1 Infections and their Role in Pathogenesis and the Enhancement of Virulence

“…IL-6 expression was shown to be significantly higher in the lungs of HK/483-infected mice compared with mice infected with HK/486 [75]. Increases in levels of IL-6 expression in the sera or brains of mice infected with highly pathogenic H5N1 strains were associated with hypercytokinemia [78] and increases in mortality, respectively [70,79,80]. These results support previous studies in which IL-6 was markedly elevated in the sera and cerebrospinal fluids (CSFs) of infected mice displaying signs of encephalopathy [81,82].…”

“…Studies of H5N1 infections in IFN-or IFN signaling-deficient mice have not yet been reported. However, infection with the highly pathogenic human (HK/483) or avian (A/duck/Tuva/01/06) H5N1 viruses induced lower IFN-responses in the lungs and markedly increased levels of expression in the brain [70], and elevated sera levels [78]. It remains to be determined whether suppression of pulmonary IFN-responses have a role in reducing levels of viremia.…”