Looking further afield

03 June 2014
By Eva Archer

Electron micrograph of the Rabies Virus. Credit: CDC/ Dr Fred Murphy

Electron micrograph of the Rabies Virus. Credit: CDC/ Dr Fred Murphy

Although no one at the Wellcome Trust Sanger Institute studies rabies viruses, Charlotte Houldcroft and I decided to write about them for a Nature Reviews Microbiology Genome Watch column because the methods required to track and sequence rabies viruses are similar to the methods we use in the Pathogen Genetics team for viruses such as MERS-Coronavirus and HIV. There’s a lot that can be learned from keeping a close eye on research in different but related fields.

Since 2003, scientists at the Sanger Institute have written regular reviews for Genome Watch with a broad focus on bacteria, viruses, fungi, and unicellular eukaryotic organisms. The column is great for highlighting recent publications that use genomics to further microbiological research and focuses on a different pathogen or technology each month to alert researchers of new data.

Review articles are an important part of the scientific publication process and are an invaluable resource for students and researchers. They summarise dozens, if not hundreds, of publications and put recent discoveries into context for a given research area. Genome Watch is not a full-length review, but still offers a valuable lesson in recapitulating and summarising recently published work.

Rabies, which is caused by lyssaviruses, is fatal if untreated and leads to an estimated 55,000 deaths worldwide each year. It’s particularly interesting for us because, as a zoonotic disease (meaning it is transmitted from animals to human), understanding where animals are infected and with which strain of the virus is important for tracking disease spread and potential outbreaks.

We wanted to emphasise the importance of tracking rabies virus genomes across species and over time to predict the emergence of lethal strains in humans. We also wanted to tie in both clinical and basic scientific applications, so the papers we selected were: a case study of a rabies fatality in Australia from an undetected lyssavirus infection, and two genome sequencing studies of lyssavirus from skunks, foxes, and dogs.

Clinically, genomes are critical to making the right diagnosis: rabies can be diagnosed by polymerase chain reaction, a process that amplifies a small known section of RNA, but this method will just recognise the most common strains. To detect all cases, you need to sequence the entire rabies virus, then you’ll be able to see how the virus is adapting and changing. On a basic scientific level, the ability to accurately detect and track single mutations (which can affect virulence and transmission of the virus) matters not only for rabies viruses, but for other viruses and pathogens.

Although neither of us knew much about lyssaviruses, as virologists at the Sanger Institute we are well acquainted with some of the methods used to sequence and analyse virus genomes, as well as the hazards and problems faced, especially in detecting rare mutations and assembling full genomes from limited samples.

Writing reviews like this is valuable because they force you to focus on someone else’s work in an area where you have less expertise. For us, this meant reading and researching very carefully, immersing ourselves in the language and material of another area, and taking a very neutral, unbiased approach to the paper we chose to present. You don’t want the authors of the publications you are writing about to call you up because you’re misquoted or misread their work!

It’s also a nice opportunity to explore the literature outside your immediate field and learn about the latest research in pathogens and genomes.

Eva Archer is a PhD student in the NIH-Oxford-Cambridge Scholars Program. She works with Paul Kellam in the Virus Genomics group and with Richard Koup and Daniel Douek at the Vaccine Research Center, National Institute of Allergy and Infectious Disease, studying immune repertoires in SIV infection.

References

  • Archer E and Houldcroft C. (2014) Rabid about whole lyssa genomes. Nature Reviews Microbiology. DOI:10.1038/nrmicro3263

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