The current understanding of respiratory mucus has revealed a complexity and functionality far beyond the classical role ascribed to it. Much of this knowledge has come from studying mucins, the large, heavily glycosylated, multi-domain proteins that give mucus many of its physical properties. The interaction between mucins and respiratory pathogens is also more complicated than mere entrapment. Mucins have been revealed to play an integrated role in the host response to pathogens, both before and during the immune response, and the absence or disturbance of this role can be highly detrimental to the host. Despite the importance of mucins, current understanding of their functions is limited, which is partly due to the complexity of mucus and its interactions.
Mucus appears to be an important host barrier to influenza viruses. The NA protein of influenza has been shown to be important in evading this barrier, such that viruses with low NA activity, or viruses treated with NA inhibitors, are severely impeded by mucus in vitro. Interestingly, these viruses can still infect animals and be transmitted, however, this transmission is severely attenuated, pointing to a role of respiratory mucus in viral transmission, which is not understood. Also not understood is the potential role of mucus as a host-restriction factor for influenza viruses. In vitro data suggests that respiratory mucus could be a host restriction factor between swine and human hosts, but is this also true in vivo, and is it also true between other hosts of influenza viruses? If so, is this restriction merely due to the sialic acid content of mucus or are there other components involved? Could mucus be an important selective pressure for transmissible viruses? Answering these questions is made more difficult by the complexity of mucus and the incomplete characterization of it. Therefore, further understanding of both mucus and the mucus-influenza virus interaction is likely to continue to provide insights into influenza virus transmission, host restriction and viral adaptation to new hosts that could be invaluable in understating the genesis of new strains of influenza virus.
