
In this lecture you'll apply your skills in phylogenetics and motif analysis to the study of Avian Influenza Virus (AIV). This is a 'scenario-based' exercise - meaning that like the SARS activity, this is the real deal. The Avian Influenza Virus, and the H5N1 serotype in particular, has the potential to cause a global pandemic of historic proportions. Research into Avian Influenza actually began in the early 1990s when biotechnology and bioinformatics tools allowed us, for the first time, to study a pathogen that caused massive death almost 100 years ago. We are almost as vulnerable to a pandemic of equal, if not larger, proportions, but we have a number of tools now that we did not have in 1917/1918.
Firstly, we have global communications, a healthcare infrastructure, and the ability to quickly observe, and respond, to a broad and virulent pathogenic outbreak. Secondly, we have the ability of isolate and characterize pathogens far more quickly, and apply medical triage that we did not have in the 1918 pandemic. Thirdly, and most importantly, we have the ability to rapidly sequence entire viral genomes, and use bioinformatics to determine if key antigenic shifts have occurred. It was a study in 2005 which for the first time compared the sequences of entire viral genomes that gave us insights into how avian influenza (bird flu) becomes as deadly as it is when infectious in human populations.
That is the focus of this exercise, which is a significant amount of work. You will fist read about the infamous 'Spanish Flu', and next search for, download, and format various influenza sequences. Next you'll perform alignments of HA and NA proteins, which will help you compare viral serotypes, and understand how and where they change. Next, you'll perform the key motif analysis on the NS1 gene / protein, which is the key 'signature' of an Influenza A serotype. This will allow you to instantly determine if a viral outbreak contain san avian signature in the key internal 'killing' gene.
All of the exercises below are described in more detail on the Influenza link.
Influenza - Influenza primer. What is Influenza? How does the Influenza genome work? What are the key proteins? What are serotypes? Antigenic drift vs. antigenic shift, and recombinomics. How do flu vaccines work?
Influenza - Avian Influenza Virus (AIV). What are the serotypes? What makes avian influenza so deadly?
Influenza - Phylogenetics analysis of HA protein. Comparing many serotypes of Avian Influenza, the multiple alignments of the HA protein allow for construction of an evolutionary tree. From this you can see where the 'Spanish Flu' of 1918 falls into the spectrum of many different strains of influenza.
Influenza - Phylogenetics analysis of NA protein. This essentially the same exercise as comparing the HA protein above. The sequences for this exercise are listed in an Excel table and are part of a zipped archive of folders and files.
Influenza - Motif analysis of NS1 protein. You'll start this effort by reading the paper on whole genome analysis of influenza, and then following the directions from this link, which describes the motif analysis of the NS1 protein.
This is a complex set of tasks, and may take you more than one week to complete. There is no rush to complete this entire exercise, but if you are able to do the phylogenetics and the motif analysis, you will have a very good foundation for both understanding AIV, as well as extending these skills to other studies.