The importance of model systems: Why we study a virus on the brink of global eradication
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{"title"=>"The importance of model systems: Why we study a virus on the brink of global eradication", "type"=>"generic", "authors"=>[{"first_name"=>"Julie K.", "last_name"=>"Pfeiffer", "scopus_author_id"=>"7102362156"}], "year"=>2017, "source"=>"PLoS Pathogens", "identifiers"=>{"sgr"=>"85018239520", "pui"=>"615826912", "issn"=>"15537374", "doi"=>"10.1371/journal.ppat.1006330", "scopus"=>"2-s2.0-85018239520"}, "id"=>"bb67aa50-a7fb-3fbb-bbfd-0630d182b7f4", "abstract"=>"I wouldn't be surprised to find my work on a politician-generated list of \" ridiculous, wasteful \" research projects: \" Scientists examine how poop bacteria activate polio, an eradicated virus. \" I have worked on poliovirus for 16 years. We work on other viruses too, but poliovirus has led to some of our most important discoveries. Many people only know polio as a paralytic disease that was eradicated from the United States decades ago. So why are we studying an eradicated virus? Poliovirus is an incredible model system. It grows like a weed. We can make virus stocks containing 10 10 infectious viruses without even trying very hard. For perspective, if these 10,000,000,000 viruses were dollar bills, the stack would be 68 miles high. Working with polio-virus is safe due to vaccination. We can make targeted mutations in the genome and generate mutant polioviruses within days. There are mouse strains that can be infected. Most impor-tantly, poliovirus has been studied for over 100 years. We know a lot about poliovirus and we have great tools in our toolbox. If you're going to tackle a tough problem, it helps to have a great toolbox. For other fields, the ideal toolbox may be fruit flies, worms, or yeast. Collectively, these model systems have illuminated biology and have led to major advancements in human health. What have we learned using poliovirus? As a postdoctoral fellow in Karla Kirkegaard's lab, I used poliovirus to show that RNA viruses benefit from a sloppy replication strategy. Many viruses, including Ebola, Zika, and influenza, have RNA as their genetic material. Replication of RNA by viral enzymes generates mutations, like a fast typist without spellchecker. Most of these mutations are damaging to the virus, but some can be beneficial. By isolating a mutant poliovirus that generated fewer muta-tions, I showed that a sloppy replication strategy benefits the virus by conferring adaptability during infection of animals. Marco Vignuzzi, then in Raul Andino's lab, published similar results. Long story short, Marco and I began as competitors but are now great friends (see https://storify.com/HarmitMalik/on-one-of-the-enduring-friendships-in-virology). Marco's lab has since shown that other viruses, including chikungunya, also rely on sloppy replication for optimal fitness. Several groups are exploring viruses with altered fidelity as vaccine candi-dates. In the end, our work with poliovirus was applicable to many viruses and may lead to new vaccine strategies. Over the past several years, my lab has shown that intestinal bacteria promote infection with poliovirus and other gut viruses. When we used antibiotics to deplete bacteria from mice, poliovirus replication and disease was reduced. We found that poliovirus sticks to bacteria, which aids viral infection and transmission. Tatyana Golovkina's lab showed similar effects for another model virus, mouse mammary tumor virus, and our papers were published together. Since then, several groups have shown that a variety of gut viruses rely on intestinal bacteria PLOS Pathogens | https://doi.org/10.1371/journal.ppat.", "link"=>"http://www.mendeley.com/research/importance-model-systems-we-study-virus-brink-global-eradication", "reader_count"=>2, "reader_count_by_academic_status"=>{"Student > Bachelor"=>1, "Student > Ph. D. Student"=>1}, "reader_count_by_user_role"=>{"Student > Bachelor"=>1, "Student > Ph. D. Student"=>1}, "reader_count_by_subject_area"=>{"Agricultural and Biological Sciences"=>1, "Biochemistry, Genetics and Molecular Biology"=>1}, "reader_count_by_subdiscipline"=>{"Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}}, "group_count"=>0}

Scopus | Further Information

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