3.3. Influenza B Viruses Use Siaα2,3/2,6Gal Receptors
In 1940, a new serotype of influenza viruses was isolated and designated type B. The first strain was named B/Lee/1940. Influenza B viruses have continued to cause respiratory disease in humans with antigenic change. Although HA and NA antigenic differences within influenza B viruses (IBVs) are not sufficient to separate antigenic subtypes, there were sufficient antigenic differences to classify IBVs into two lineages: (i) Victoria lineage B/Victoria/2/1987-like and (ii) Yamagata lineage B/Yamagata/16/1988-like viruses [170]. Consequently, morbidity and mortality-associated seasonal influenza is currently caused by the two lineages of IBVs and two subtypes of IAVs, 1968-derived H3N2 and 2009-derived H1N1 viruses. In contrast to IAVs, IBVs infect mainly humans, although there are sporadic reports of IBV infection in seals, pigs, horses, pheasants and dogs [65]. Similar to IAVs, IBVs have eight (-)ssRNA genome segments and possess receptor-binding and -destroying activities on different molecules, homo-trimeric HA and homo-tetrameric NA glycoproteins. Clinically approved NA inhibitors (NAIs), including zanamivir, oseltamivir, laninamivir and peramivir, are now used for treatment of infection with not only IAVs but also IBVs [171]. Several chemical compounds that have been developed as anti-influenza A NAs, including Neu5Ac2en mimetics for minimizing side effects on human Neu1-Neu4 enzymes [172,173] and NA covalent inhibitors for irreversible NA inhibition [174] and Psidium guajava Linn. (guava) tea [175] and povidone-iodine that possess anti-influenza A sialidase activities [176] might be able to inhibit influenza B viruses.
Receptor binding specificity determines the site of virus infection. It appears that wild-type influenza B/Victoria HAs possessing G141, R162 and D196 [67] and B/Yamagata HAs with F95 and N194 [68] clearly exhibit binding preference to human-type α2,6Neu5Ac receptors. Investigation of receptor binding preference of IBV clinical isolates in Taiwan during the period from 2001 to 2007 (Table 1) revealed that (i) 83% of Yamagata-like strains prefer α2,6Sia receptors, whereas 17% of them prefer both α2,3Sia and α2,6Sia and (ii) 54% of Victoria-like strains prefer both α2,3Sia and α2,6Sia, whereas 25% of them prefer sulfated glycan, either β-Gal-3-sulfate or 6-HSO3-Galβ1,4GlcNAc, and 21% of them prefer α2,6Sia. The viruses with dual α2,3Sia and α2,6Sia-binding preferences were shown to be associated with bronchopneumonia and gastrointestinal symptoms [66]. These findings indicate that the evolution of receptor binding specificity in IBVs in circulation is different from that in IAVs and indicate tissue tropism and pathogenicity of IBVs, possibly affecting virus transmission.