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SC-INBRE at Winthrop

The Westover Lab

Host-Viral Interactions: The Evolution of Viruses in Response to Host Selection Pressure

 Westover, Kristi   Name:  Kristi Westover 
Title:  Associate Professor of Biology 
Ph.D., Botany, Washington State University, Pullman, Wash.
B.A., Biology, Hamline University, St. Paul, Minn.
Office:  216 Dalton Hall  
Phone:  803/323-2111 x6180 
Bioinformatics, Host-Parasite Interactions, Viral Evolution

SC-INBRE Research

Influenza A H5N1 Evolution

The spread of the highly pathogenic and potentially pandemic avian H5N1 influenza strains threatens not only birds, but other non-avian hosts, such as swine, and canines, and humans.  Within the last year, avian strains of influenza A epidemic have been documented in many hosts including swine and humans.  Two of the most alarming epidemics are ongoing in Indonesia and Egypt, where morality rates in humans are extremely high.   The evolution of the virus has amplified its ability to spread from mammal to mammal and due to biochemical similarities, there is worry for increasing transmission of the disease from pigs to humans. Research in our lab is currently directed at characterizing rates of evolution in influenza A H5N1 strains from several geographic locations around the world.
Complete genomes of Indonesian and Chinese influenza A H5N1 strains from avian, swine, and human hosts were collected, translated, and aligned.  To date, phylogenetic reconstruction has been completed using the PB2 segment for Indonesian and Chinese swine sequences.  Initial results from analysis of the PB2 segment, which plays a significant role in the polymerase enzyme during DNA replication and the initiation of transcription, show a significant relationship between the Chinese strains form the Henan and Anhui provinces and the Indonesia strains. We intend to expand the analysis to include complete genomes, as well as repeat the phylogenetic work with all Indonesian hosts.  Further analysis of the swine, avian, and human H5N1 strain may give insight into the transmission of the disease in Asian countries and supply information on future strain adaptations and possible eradication. 
Most human cases of H5N1 have occurred from dealing with infected birds. Although human to human transfer is rare, it poses the greatest risk to the human population. Since flu viruses have the tendency to mutate on a regular basis, it is only a matter of time before the virus mutates into a pandemic producing virus. Egypt, in the last couple of years has become an H5N1 hotspot for both bird and human cases. Since January 20, 2011, according to the WHO, the number of cases is up to 121 and a total of 40 fatalities. This places Egypt behind only Indonesia in the number of human cases and behind Indonesia and Vietnam in the number of fatalities. Since Egypt is a major hot spot for H5N1 infection, it is important to find how and where the virus is mutating.  To date, 375 Indonesian sequences have been collected, aligned, and analyzed for host specific variability in 14 known and/or predicted CTL sites.  There appear to be several examples of epitopes that would make good vaccine targets.  We plan to finish this analysis in the month of May. 

Codon usage in the proteins of Foot and Mouth Disease Virus (FMDV)

In order to understand the reproductive success of viruses and their interactions with host organisms, it is crucial to examine DNA usage as it relates to the production of individual proteins. We intend to examine a system where we can expect noticeable codon across the genome in addition to looking at bias in the individual proteins where known antigenic epitopes are located. Foot-and-mouth disease virus (FMDV) provides an excellent model with which to study codon usage due to its manageable genome size and the easy availability of hundreds of genomes. We collected nucleotide sequences for all complete genomes of FMDV. Sequences were translated, aligned and Relative Synonymous Codon Usage (RSCU) was estimated across the genome for individual serotypes. There was clear evidence of RSCU bias across the entire genome for almost every amino acid in every serotype. Our results to date agree with what has been found in previous studies of codon usage in other vertebrate DNA viruses; however, we intend to examine the FMDV genomes in more depth by examining codon usage within individual proteins in addition to whole genomes of each serotype.   We plan to continue this work over the coming summer.