One such host factor that may limit zoonotic transmission is the difference in host temperatures between avian and human tissues that are susceptible to influenza virus infection. Avian influenza viruses are adapted for replication in the avian enteric tract at 40-41uC . While the surface temperatures of the human respiratory tract are variable, a temperature gradient clearly exists in which the surface temperature of the proximal large airways (i.e., nasal and tracheal) average 32+/20.05uC while temperatures of the smaller, distal airways (i.e., bronchioles) are closer to that of the core body temperature, 37uC [18, 19] . While multiple transmission routes have been described for influenza viruses, the proximal airways likely represent a predominant site for human influenza virus inoculation as they provide a large exposed surface area of virus-susceptible epithelial cells [20] . These cells are directly accessible by large droplet aerosols and by way of digital inoculation of the nasopharynx and conjunctival mucosa [12, 21] . Inefficient infection by avian influenza viruses, even in the presence of a2,3-linked SA, may be due to the cooler temperature of the proximal airways compared to that of the distal airways/lung regions where H5N1 avian influenza viruses appear to replicate efficiently [22] .