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

Abstract

Infection of host cells with the influenza virus is mediated by specific interactions between the viral hemagglutinin and its cell receptor, oligosaccharides containing sialic acid (SA) residues. Avian and human influenza viruses preferentially bind to α-2, 3-linked and α-2, 6-linked sialic acids, respectively. Therefore, differential expression of these receptors may be crucial to influenza virus infection. To date, the distribution of these two receptors has never been investigated in the tissues of BALB/c mice, which is the routine animal model for influenza research. Here, the expression pattern of alpha-2,3 and alpha-2,6 sialic acid-linked receptors in various organs (respiratory tract, gastrointestinal tract, brain, cerebellum, spleen, liver, kidney and heart) of BALB/c mice were determined. Histochemical staining of mouse tissue sections was performed by using biotinylated Maackia amurensis lectin II (MAAII), and Sambucus nigra agglutinin (SNA) were performed to detect the alpha-2,3 and alpha-2,6 sialic acid-linked receptors, respectively. The results showed that the alpha-2,3 and alpha-2,6 sialic acid-linked receptors were both expressed on trachea, lung, cerebellum, spleen, liver and kidney. Only the epithelial cells of cecum, rectum and blood vessels in the heart express the alpha-2,6 sialic acid-linked receptors. The distribution patterns of the two receptors may explain why this model animal can be infected by the AIV and HuIV and the pathological changes when infection occurred. These data can account for the multiple organ involvement observed in influenza infection and should assist investigators in interpreting results obtained when analyzing AIV or HuIV in the mouse model of disease.

Fecal Influenza in Mammals: Selection of Novel Variants

“…This is most likely due to the expression of ␣-2,3 sialic acid receptors in mouse models (51,52). Increased fusion pH is associated with increased virulence in mice (42).…”

Specific Sites of N-Linked Glycosylation on the Hemagglutinin of H1N1 Subtype Influenza A Virus Determine Sensitivity to Inhibitors of the Innate Immune System and Virulence in Mice

“…Although resistance to neutralizing proteins in BAL is likely to be a major factor contributing to virulence of H1 IAV, other intrinsic features of HA contribute to enhanced PR8 replication in the airways. Receptor specificity differences between Brazil [specificity for a(2,3)-Gal and a(2,6)-Gal-linked SA] and PR8 [specificity for a(2,3)-Gal-linked SA] are likely to be important, as a(2,3)-Gal-SA is the predominant linkage expressed in mouse lung (66,67). Moreover, studies have demonstrated that adaptation of human influenza viruses to growth in mouse lung is associated with a switch in receptor specificity to favor binding to mouse respiratory cells (61,62).…”

Virulence and transmissibility of H1N2 influenza virus in ferrets imply the continuing threat of triple-reassortant swine viruses

“…We further noted that the HA 225G residue enhanced virus growth in ferret lungs, consequently inducing marked lung pathology. The CT-Sw/1204 virus also became virulent in BALB/c mice known to express predominantly α2,3-sialic acid in their lungs (24), and demonstrated enhanced infectivity and growth in human lung tissues, indicating potentially productive pulmonary replication. Notably, severe viral pneumonia attributed to efficient virus attachment to α2,3-sialic acid glycoconjugates deep in the lungs have been observed in H5N1 (25) and HA 225G variants of the pH1N1 (5,(26)(27)(28)(29)(30) virus infections.…”