ABSTRACT
Subtype H6 influenza A viruses (IAVs) are commonly detected in wild birds and domestic poultry and can infect humans. In 2010, a H6N6 virus emerged in southern China, and since then, it has caused sporadic infections among swine. We show that this virus binds to α2,6-linked and α2,3-linked sialic acids. Mutations at residues 222 (alanine to valine) and 228 (glycine to serine) of the virus hemagglutinin (HA) affected its receptor-binding properties. Experiments showed that the virus has limited transmissibility between ferrets through direct contact or through inhalation of infectious aerosolized droplets. The internal genes of the influenza A(H1N1)pdm09 virus, which is prevalent in swine worldwide, increases the replication efficiency of H6N6 IAV in the lower respiratory tract of ferrets but not its transmissibility between ferrets. These findings suggest H6N6 swine IAV (SIV) currently poses a moderate risk to public health, but its evolution and spread should be closely monitored.
Subject(s)
Influenza A virus/isolation & purification , Influenza A virus/physiology , Orthomyxoviridae Infections/veterinary , Sialic Acids/metabolism , Swine Diseases/transmission , Swine Diseases/virology , Virus Attachment , Animals , China , Hemagglutinin Glycoproteins, Influenza Virus/genetics , Hemagglutinin Glycoproteins, Influenza Virus/metabolism , Influenza A virus/pathogenicity , Mutation, Missense , Orthomyxoviridae Infections/transmission , Orthomyxoviridae Infections/virology , Protein Binding , Receptors, Virus/metabolism , SwineABSTRACT
Exhaustive dihydroxylation of the pair of cyclooctadienols consisting of 4 and 5, which are available in enantiomerically pure form from d-glucose, resulted in the formation of two diastereomeric tetraols in each case. The difference in polarity of the 6/7 and 8/9 pairs facilitated their chromatographic separation. Ensuing acetylation and PMB deprotection allowed for the assignment of relative (and ultimately absolute) stereochemistry to the resulting monohydric alcohols on the basis of J(HH) analysis of their (1)H NMR spectra. The highly functionalized exomethylenecyclooctanes 14-17, which were derived by periodinane oxidation and Wittig olefination, were further elaborated by hydroboration and global deprotection. The eight members of the cyclooctanose family of carbasugars and their precursor intermediates consistently showed patterns of J(HH) values in line with the contiguous stereochemical relationships. Also assayed was their specific inhibitory behavior toward glycosidases.
