Since the avian virus isolates used in these experiments are neither derived from samples obtained from humans nor passaged in human cells in vitro, we next investigated whether growth attenuation at low temperatures would be retained in a highly pathogenic H5N1 (A/VN/1203/04) influenza virus isolated from a fatal human case [34] . We compared infection kinetics of H5N1 (A/VN/1203/04) at 33uC and 37uC on HAE using A/Udorn/ 307/72 in parallel cultures as a human influenza virus control. As described above, A/Udorn/307/72 grew with similar kinetics at 33uC and 37uC ( Figure 3B ). A/VN/1203/04, however, exhibited slower replication kinetics at 33uC when compared to that for 37uC ( Figure 3D ). Indeed, titers were significantly decreased at 33uC vs. 37uC at 24, 48 and 72 hrs pi. In addition, only at 37uC did A/VN/1203/04 approach similar peak titers as the human A/ Udorn/307/72 virus by the end of the 72 hr time course ( Figure 3D ). Histological analyses of A/VN/1203/04-infected HAE at either temperature showed absence of obvious CPE in sharp contrast to A/Udorn/307/72 that obliterated the epithelium by 72 hrs pi ( Figure 3E ). The lack of obvious CPE after H5N1 infection contrasts reports that H5N1 induced extensive apoptosis in mammalian airway cells [35, 36] . The fact that we did not observe obvious CPE with this highly pathogenic virus warrants further investigation but is in line with the limited cell damage shown following infection with A/Dk/Eng/62 for 72 hrs ( Figure 2B ). In sum, using diverse examples of human and avian influenza viruses we have shown that avian influenza viruses, but not human influenza viruses, are restricted for infection and growth in HAE at the lower temperature of 32uC.