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4.3: Suspicious Outbreak - Overview

MEMORANDUM

 

To:

BIP Interns

From: BIP Project Leader
Subject: Suspicious Outbreak!  Is it Avian influenza?

We have some exciting work for you and your team.

Wild birds constitute a large reservoir of genetically diverse strains of influenza. Although many of these strains are restricted to infecting birds, the possibility exists that a genetic change in any one strain could allow it to infect humans as well as avian hosts. If that were to happen, and a new avian virus were to emerge that could be transmitted easily between human hosts, it would pose a serious threat to human health. Many people have some immunity to the influenza strains that currently circulate in the human population however, the HA and NA proteins on the surface of avian viruses are somewhat different and unlikely to be recognized by existing antibodies. If the human immune system responds too slowly, there’s an increased likelihood of severe disease and possible death.

Eventually, we would like to be able to look at an influenza genome and know from the sequence if that virus is a threat to human health. Right now, our abilities are more limited. We can however, compare the sequences of newly isolated viruses with the sequences of viruses whose properties are better characterized and make some predictions about what the new virus can do. We can also determine where the virus originated and where it acquired new mutations or new pieces of RNA.

One of the viruses we’re watching most intently is the highly pathogenic form of H5N1. H5N1 has severely impacted both wild and domestic birds and clusters of human infections have appeared in several countries including China, Viet Nam, Thailand, Indonesia, Turkey, Iraq, Azerbaijan, and Egypt.

We’re going to examine a set of influenza sequences from an Indonesian family who became infected in 2005 and determine if they were infected with an avian strain, and whether reassortment or recombination may have occurred. These same skills can be applied later to answer questions about more recent outbreaks.

Please refer to the Requirements for instructions on how to proceed. After performing the analyses and reflecting on your results from the sequence alignments, phylogenetic trees, and the identification of a motif in the NS-1 protein; answer these questions:

  • Were the Indonesian outbreaks birdlike? Were the viral proteins more similar to proteins from avian influenza or to viral proteins from a human strain?
  • How similar were the influenza viruses from different family members and their cat? Was everyone in the family infected by the same virus? Is there another way to explain all why all the family members might get sick? Use the data from the sequence alignment to support your conclusion.

If an epidemic does begin, there are other questions that we could address using bioinformatics tools. For example:

  • Would our current vaccine strains be likely to protect against a new epidemic strain? What could we do to predict the answer?
  • Could Tamiflu® be used to control infection with this virus? Is there a way we could predict the answer by using sequence information?

When you have gathered your evidence, it is time for your team to review your findings and collaborate on a presentation. You will make your presentation to your peers as well as a few involved scientists here at the NIH and from the WHO. Plan on no more than 20 minutes, including questions – so you will need to be organized.

Deliverables:

  1. Data sets for all influenza proteins
  2. Images for each of the phylogenetic trees.
  3. A 20 minute presentation

This is challenging, important work. Good luck!

 

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