Science Buddies: "Ask an Expert"

Can a transmembrane protease serine cleave the hemagglutinin of the H5N1 Avian Influenza Virus? If so, is it possible to modify the sequence of that protease? Also, is trypsin/furin similar to this enzyme, or are there huge differences among them?

Thanks

NovaStar15,

As a quick caveat, this topic is a little bit outside my area of expertise. However, a search through the scientific literature (google scholar is my search engine of choice) reveals that several recent papers have been published demonstrating that Transmembrane Protease Serine 2 and 4 (TMPRSS2/4) are among the serine proteases that can cleave the hemagglutinin of Avian Influence Virus (also known as Influenza A viruses). Here is a link to the most relevant paper, which looks at TMPRSS2 and it's ability to activate and likely cleave hemagglutinin of several difference types of Avian Influenza virus: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3614188/. H5N1 was not specifically studied in this publication, but, based on the fact that TMPRSS2 can cleave hemagglutinin from several other types of avian influenza virus, it seems like a reasonable hypothesis that it can cleave the hemagglutinin of the H5N1 Avian Influenza Virus.

For what purpose do you want to modify the sequence of the TMPRSS2 (or 4) protease? What is the specific hypothesis that you have?

Lastly, Trypsin, which published literature has shown can cleave the hemagglutinin of the H5N1 Avian Influenza virus, will share several characteristics with TMPRSS2, since they are both serine proteases. However, they have different substrate specificity. Trypsin's substrate specificity is classified as trypsin-like, while TMPRSS2 is classified as chymotrypsin-like. Please let me know if you would like more information on this topic and we can do a bit of a deeper dive.

Josh