Evolving complexities of influenza virus and its receptors

Sialic acids (Sias) are regarded as receptors for influenza viruses and are usually bound to galactose (Gal) in an alpha 2-3 or alpha 2-6 configuration. The detection of these Sia configurations in tissues has commonly been through the use of plant lectins that are able to identify which cells contain Sia alpha 2-3- and Sia alpha 2-6-linked glycans, although other techniques for receptor distribution have been used. Initial experiments indicated that avian versus human influenza virus binding was determined by either Sia alpha 2-6 or Sia alpha 2-3 expression. In this review, we suggest that the distribution and detection of these terminal Sia alpha 2-3- and Sia alpha 2-6-linked receptors within the respiratory tract might not be as clear cut as has been reported. We will also review how other viral and receptor components might act as determinants for successful viral replication and transmission. Understanding these additional components is important in comprehending the infection and the transmission of both existing human influenza viruses and newly emerging avian influenza viruses.