Transcript--Have You Heard? The protective power of the nose

Untitled Document

The nose, that nidus of the flu and colds in people, may be a lifesaver when it comes to avian influenza viruses. A study in PloS Pathogens reveals that the cooler climate in human nasal cavities keeps avian viruses from replicating efficiently enough to cause infection.

In people, the proximal large airway, which includes the nasal cavity and trachea, has an average surface temperature of 32 C. In birds, avian influenza viruses thrive and replicate in the gut, which has an ambient temperature of 40 to 41 C. Influenza viruses are most commonly transmitted to people through the nose, so when an avian virus is introduced into the nasal cavity, it is not able to get warm enough to replicate efficiently.

A team of researchers investigated various combinations of human and avian influenza viruses in vitro to arrive at these results. First, the researchers compared a human H3N2 virus with an avian H4N6 virus. They used human ciliated airway epithelium, which has been shown to mimic the features of human airway epithelium in vivo, as their in vitro model. The ciliated airway epithelium was inoculated with both viruses, and the researchers observed the results of replication at two different temperatures, 37 C and 32 C, after 48 hours. The human H3N2 virus readily grew at both temperatures. The avian H4N6 virus also grew at 37 C, but replication was slow to nonexistent at 32 C. When they examined the number of cells that died from the virus, far fewer were killed in the avian virus samples, demonstrating the virus was not able to take hold and spread.

To establish that these findings weren't just applicable to the specific influenza strains tested, the researchers also inoculated human ciliated airway epithelium with two additional H3N2 human influenza viruses and with a randomly selected H5N3 avian virus. In this case, the human influenza viruses replicated as expected, but the H5N3 avian virus showed no growth or spread at all at 32 C.

Next, they obtained a sample of a highly pathogenic H5N1 avian virus from a person that had died of the disease. When they compared replication at 33 C and 37 C, they found that the virus replicated much slower at 33 C.

At this point, it seemed apparent that surface temperature indeed played a role in virus replication. To determine what was responsible for this temperature sensitivity, they genetically altered human influenza viruses by adding avian virus glycoproteins. Again, the genetically altered viruses replicated more slowly at 32 C. Through this series of experiments, they found that temperature sensitivity appears to be linked to the glycoproteins hemagglutinin and neuraminidase.

We all know that avian influenza viruses are rarely transmitted to people. However, when they do occur, the results can be deadly. This study's findings illuminate one of the mutations avian influenza viruses must undergo in order to become pathogenic in people and may help identify which strains are more likely to become a threat to human health. The researchers pointed out that the strains of avian influenza virus that do infect people tend to manifest in the distal airways and lungs, which makes sense since the temperature in these areas, which averages 37 C, is closer to the environment that the virus thrives in in birds. But the viruses have to reach the distal airways first. And, as this study shows, it's tough to get past the nose.

Source: Scull AM, Gillim-Ross L, Santos C, et al. Avian influenza virus glycoproteins restrict virus replication and spread through human airway epithelium at temperatures of the proximal airways. PLoS Pathog 2009;5(5):e1000424.