{"id":6577,"date":"2011-05-19T14:31:09","date_gmt":"2011-05-19T14:31:09","guid":{"rendered":"http:\/\/d45h139.public.uconn.edu\/sites\/news\/?p=6577"},"modified":"2025-01-31T11:26:47","modified_gmt":"2025-01-31T16:26:47","slug":"team-to-sequence-poultry-viruses-2","status":"publish","type":"post","link":"https:\/\/today.uconn.edu\/2011\/05\/team-to-sequence-poultry-viruses-2\/","title":{"rendered":"Team to Sequence Poultry Viruses"},"content":{"rendered":"

An interdisciplinary team of researchers from UConn and Georgia State University received more than $400,000 from the U.S. Department of Agriculture (USDA) to develop computational methods enabling the characterization of genomic diversity of a particularly contagious avian bronchial virus.\u00a0 The disease costs U.S. poultry farmers millions of dollars each year in lost revenue.\"\"<\/a><\/p>\n

Dr. Ion Mandoiu<\/a>, an associate professor of Computer Science & Engineering and the principal investigator on the project, is partnering with Drs. Mazhar I. Khan<\/a> of Pathobiology & Veterinary Medicine, Rachel O\u2019Neill<\/a> of Molecular & Cell Biology, and Alex Zelikovsky<\/a> of Georgia State University. The grant was made by USDA\u2019s National Institute of Food & Agriculture<\/a>.<\/p>\n

The team is focusing on an infectious bronchitis virus (IBV) that is the biggest single cause of economic loss in the U.S. poultry industry.\u00a0 While generally not fatal except among young chickens, IBV restricts growth in broiler chickens and reduces egg production in layers.\u00a0 Like most bronchial diseases, it spreads rapidly in the dense living conditions found on most commercial poultry farms.<\/p>\n

To reduce infection rates, farmers inoculate their poultry using live vaccines.\u00a0 In live vaccines, the virulent portion has been removed or weakened, but enough of the viral material remains to produce an immune response in the animal.<\/p>\n

Dr. Khan, who brings expertise as a pathobiologist, says \u201cIBV is caused by a coronavirus.\u00a0 One of the several proteins associated with it, called S1, is possibly the most antigenic and very vulnerable to point mutation. \u00a0In the U.S., the Massachusetts strain is the umbrella virus, so all vaccines against IBV contain modified live Massachusetts IBV blended with the local strain, which is designated as the name of the state in which the IBV variation is found.\u201d<\/p>\n

Chickens have to be vaccinated every year with this combination IBV because the virus mutates slightly from year to year. Dr. Khan notes \u201cThe vaccine provides broad but incomplete protection.\u00a0 For this project, in my lab we will isolate the virus collected from the vaccinated birds, focusing specifically on the S1 gene, where the greatest share of genetic variations occurs.\u201d<\/p>\n

Dr. Mandoiu explains that IBV replicates via ribonucleic acid (RNA), not DNA.\u00a0 RNA viruses are associated with very high mutation rates because RNA-polymerase, the enzyme responsible for copying the virus genome during replication, lacks what is known as \u201cproofreading capability.\u201d\u00a0 This inability to self-correct genetic errors produces a great many more mutated versions of the original species. The chicken\u2019s immune system simply cannot keep up with the barrage of attacks.\u00a0 Consequently, within any one animal there will be many IBV quasispecies present, rendering the vaccine ineffectual and keeping the disease virulent.<\/p>\n

A first step to developing more effective vaccines involves the identification of the different quasispecies and determination of the pace at which they evolve and replicate. \u201cNo one has actually measured how many quasispecies coexist in an organism,\u201d says Dr. Mandoiu.\u00a0 \u201cPrevious studies have involved cloning of the IBV virus, but this process results in maybe 20 quasispecies sequences within a single chicken. Experimental evidence suggests that quasispecies acting as a molecular memory can be present at frequencies as low as 0.1%, and these remain undetected by cloning-based approaches.\u201d<\/p>\n

Recent advances in high-throughput sequencing technologies eliminate the cloning bottleneck, generating millions of short sequence fragments, called \u201creads,\u201d in a single run.\u00a0 According to Dr. Mandoiu, reconstructing the full spectrum of viral quasispecies from these reads is a challenging computational problem due to the short read length and sequencing errors.\u00a0 \u201cIt is a real challenge to distinguish true differences from sequencing errors\u201d he says.\u00a0 This USDA project builds upon his expertise in computational genomics, including his 2006 National Science Foundation Early Career Development (CAREER) award for work involving combinatorial algorithms for high-throughput collection and analysis of genomic diversity data.<\/p>\n

\"\"<\/a>Dr. Zelikovsky, also a computer scientist, collaborates with Dr. Mandoiu in developing the sophisticated algorithms needed to piece together these short reads.\u00a0 \u201cThe genetic profiles of different quasispecies are highly similar; two quasispecies sequences may differ at just a few nucleotides\u201d says Dr. Zelikovsky.\u00a0 \u201cExisting assembly algorithms ignore such small differences, and produce a single \u2018consensus\u2019 sequence. Our goal is to reconstruct the complete collection of quasispecies sequences, and also estimate the frequency of each of them.\u201d \u00a0A prototype version of these algorithms has already been tested with promising results on sequencing data for human viruses such as HIV and hepatitis C virus.<\/p>\n

For the IBV project, the team plans to comprehensively characterize the myriad IBV quasispecies infecting large poultry flocks on commercial farms. \u00a0Dr. O\u2019Neill, a genomicist, is interested in how genes and viruses evolve.\u00a0 For this project, she says, \u201cI\u2019ll be doing the sequencing within the Center for Applied Genetics and Technology<\/a> at UConn. We\u2019ll be studying amplicons, which are subregions of the virus. Our platform for the sequencing is a 454 Genome Sequencer, which will allow us to sequence up to millions of individual viral sequences from one sample or across multiple samples simultaneously.\u201d<\/p>\n

The researchers will swab the throats of live chickens at a commercial poultry farm before vaccination and, subsequently, at one-week intervals for five weeks.\u00a0 The samples will provide the genetic material for sequencing. \u201cThis is next-generation sequencing,\u201d Dr. O\u2019Neill remarks. \u201cIt\u2019s an enormous leap over the old techniques, which were done in a serial fashion.\u00a0 This technology is really the advent of personalized medicine.\u201d She estimates that the process, from receipt of the swab samples until completion of the sequencing, will take just a few days.<\/p>\n

Over the two years of the project, Dr. Mandoiu and his colleagues expect to develop user-friendly web-based bioinformatics tools that will be made available free of charge to the research community. This will allow other researchers to improve and customize the tools to their needs and create a community of users that will ensure long term maintenance and further developments.\u00a0 Dr. Mandoiu projects that the tools will be applicable to the study of quasispecies evolution and vaccine design for many viruses affecting animal health, not only IBV in poultry. \u00a0In addition, he says the work will lead to improved diagnostics and monitoring of viral outbreaks in bird and animal populations, reduced vaccination costs, improved animal health, and improved yield of animal production.<\/p>\n","protected":false},"excerpt":{"rendered":"

An interdisciplinary team of researchers from UConn and Georgia State University received more than $400,000 from the U.S. Department of Agriculture (USDA) to develop computational methods enabling the characterization of genomic diversity of a particularly contagious avian bronchial virus.<\/p>\n","protected":false},"author":122,"featured_media":224653,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"_crdt_document":"","wds_primary_category":0,"wds_primary_series":0,"wds_primary_attribution":0,"footnotes":""},"categories":[1866],"tags":[],"magazine-issues":[],"coauthors":[2110],"class_list":["post-6577","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-engr"],"pp_statuses_selecting_workflow":false,"pp_workflow_action":"current","pp_status_selection":"publish","acf":[],"publishpress_future_action":{"enabled":false,"date":"2026-05-09 11:28:55","action":"change-status","newStatus":"draft","terms":[],"taxonomy":"category","extraData":[]},"publishpress_future_workflow_manual_trigger":{"enabledWorkflows":[]},"_links":{"self":[{"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/posts\/6577","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/users\/122"}],"replies":[{"embeddable":true,"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/comments?post=6577"}],"version-history":[{"count":1,"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/posts\/6577\/revisions"}],"predecessor-version":[{"id":225041,"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/posts\/6577\/revisions\/225041"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/media\/224653"}],"wp:attachment":[{"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/media?parent=6577"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/categories?post=6577"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/tags?post=6577"},{"taxonomy":"magazine-issue","embeddable":true,"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/magazine-issues?post=6577"},{"taxonomy":"author","embeddable":true,"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/coauthors?post=6577"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}