Specific biochemical features of replication of clinical influenza viruses in human intestinal cell culture.

Influenza A viruses isolated from the respiratory tract of patients with influenza were cultured in human intestinal epithelium cells (CACO-2 line). The CACO-2 cells were found to be 100-fold more susceptible to the clinical viruses than MDCK cells and chicken embryos. On passaging in CACO-2 cells, clinical isolates of the subtype H3N2 retained the original "human" phenotype and agglutinated human but not chicken erythrocytes, whereas on passaging in MDCK cells the virus phenotype changed to the "avian" one. On comparison with laboratory strains (grown in chicken embryos or MDCK cells), the clinical viruses were characterized by higher stability of the anti-interferon protein NS1 but had a reduced synthesis of the matrix protein M1, and this could facilitate the virus adaptation and escape of the infected cells from immune attack in the human body. The increased tropism to the human CACO-2 cells correlated with higher adsorption of the clinical viruses on cellular receptors. However, in the CACO-2 and MDCK cells the ratio of sialyl-containing glycoreceptors of the 2-3 and 2-6 type was similar. These observations indicated that not only sialic acid residues were involved in the adsorption and penetration of the clinical viruses into human cells, but also the protein moiety of the cellular receptor itself and/or an additional cellular coreceptor. Thus, clinical influenza viruses are shown to possess a specific mechanism of sorption and entry into human epithelial cells, which is responsible for their higher tropism to human cells and is unlike such a mechanism in canine cells.