Infection of human airway epithelia with H1N1, H2N2, and H3N2 influenza A virus strains

Three subtypes of influenza A virus cause human disease: H1N1, H2N2, and H3 N2. Although all result in respiratory illness, little is known about how t hese subtypes infect differentiated airway epithelia. Therefore, we assayed A/PR/8/34 (H1N1), A/Japan/305/57 (H2N2), and X31 (H3N2) influenza virus st rains for binding and infection on fully differentiated primary cultures of airway epithelia isolated from human bronchus, grown on semiporous filters at an air-liquid interface. In this model system, viral infectivity was hi ghest when virus was applied to the apical versus the basolateral surface; japan was most infectious, followed by PR8. The X31 strain showed very low levels of infectivity. Confocal microscopy and fluorescence-resonance energ y transfer studies indicated that Japan virus could enter and fuse with cel lular membranes, while infection with X31 virions was greatly inhibited. ja pan virus could also productively infect human trachea explant tissues. The se data show that influenza viruses with SA alpha2,3Gal binding specificity , like Japan, productively infect differentiated human airway epithelia fro m the apical surface. These data are important to consider in the developme nt of pseudotyped recombinant viral vectors for gene transfer to human airw ay epithelia for gene therapy.