Interactions. Genetic variation affecting host proteins required for viral entry and pathogenesis may partially explain the sporadic and rare nature of avian-tohuman H5N1 transmission. Although humans do express the SAα-2,3Gal molecules that are efficiently bound by avian H5N1, their expression is usually limited to the lower respiratory tract and has only occasionally been detected in the nasal mucosa and upper respiratory tract [60, 61] . Additionally, the binding of several influenza strains to human erythrocytes is highly variable, with up to a 40fold difference between individuals tested in one study, suggesting a role for genetic polymorphism in regulating susceptibility [62] . Whether variation in the human ST3 beta-galactosamide alpha-2,3-sialyltranferase 1 (ST3GAL1) gene that produces the SAα-2,3Gal linkage affects H5N1 susceptibility is not known, but remains a possibility [63] . Interestingly, a population genetics study designed to detect human SNPs under virus-driven selective pressure found a significant enrichment of glycan biosynthesis gene SNPs associated with viral selection, including rs3758105 (intronic A/G SNP) in the ST3GAL1 gene [64] (Table 2) . Data demonstrating the infection of upper respiratory tract cells with H5N1 in vitro also suggests the presence of additional cellular receptors for the virus [61] . Alternately, prevention of viral attachment in the respiratory tract is accomplished by host proteins that can sterically hinder viral HA binding, or aggregate and opsonize the virus. These proteins include serum mannose-binding lectin 2 (MBL2) and surfactant, pulmonary-associated protein A1 and D (SFTPA1 and SFTPD, resp.). A SNP in MBL2 (230G/A), resulting in low serum MBL levels, is associated with SARS susceptibility [36, 37] , while polymorphisms in SFTPA1 and SFTPD are associated with other respiratory illnesses [65, 66] (Table 2 ). To date, none of these polymorphisms have been investigated with respect to H5N1 susceptibility.