2006 merck/merial - School of Veterinary Medicine - Louisiana State ...

purified, viral RNA was extracted and viral segments amplified by RT-PCR technology. The IA/30 H1N1 virus is geneticallyengineered with unique restriction sites in each of its 8 individual genes. Therefore, the origin of each viral segment can beeasily differentiated.Results: Reassortment occurred in pigs co-infected with the H1N1 and H3N2 viruses. All novel reassortant SIVscontained the wild-type NS-segment from the H1N1 IA/30 and the NP-segment from the modern H3N2 Tx/98 strain. Most ofthe PB2 (avian origin) and NA (human origin) genes (about 90%) originated from the H3N2 Tx/98 strain. The origin of theother four genes (PB1, PA, HA, M) are randomly derived from either the H1N1 or H3N2 SIV.Conclusions: The avian–like PB2 and the modern NP genes (H3N2) were preferentially selected into the novelreassortant SIVs. This indicates these two genes and their products might play an important role in the adaptation of novelreassortant SIVs. These studies also proved that a functional immunomodulatory NS1 protein (has interferon modulatingabilities) is critical for the survival of swine influenza viruses in its natural host, the pig.Simple Intervention to Reduce Stress and Recrudescence of Latent Herpes Virus Infections in Shelter CatsJeremy B. Page*, Sandra Newbury, Chester B. Thomas, Ronald D. SchultzSchool of Veterinary Medicine, University of Wisconsin, Madison, Dane County Humane Society, McFarland, WIFeline upper respiratory disease complex (FURDC) is a common and infectious multifactorial disease syndrome inshelter cats, most commonly initiated by feline calicivirus (FCV), feline herpesvirus (FHV), or Mycoplasma spp. Shelter catswith FURDC often are euthanized due to lack of treatment resources and the need to control the spread of infectious disease.Prevention is key to controlling FURDC in animal shelters. Stress may play a major role in the development of FURDC.Latent infection with FHV is widespread in domestic cats, and stress-induced increases in plasma cortisol can triggerrecrudescence, resulting in shedding of virus and subsequent exposure of uninfected cats. Inability to hide in response tostressors has been correlated with increased cortisol in caged cats in group housing situations. Most shelters house cats in cageswith open wire fronts, leaving stressed cats exposed. To test the hypothesis that ability to hide reduces stress and subsequentlywill reduce incidence of FURDC, a randomized prospective study comparing markers of stress and FURDC in three groups ofcats will be conducted. Cats in two intervention groups will be provided with either a box or a towel covering half of the frontof the cage. A control group will receive no hiding place. Changes in shedding of FHV and urinary cortisol:creatinine ratiowill be measured at admission and over time in the shelter. Commonly accepted stress behaviors will be monitored daily. Datawill be analyzed for differences in incidence of FURDC in each of the randomized groups, as well as correlation betweenchanges in UCCR, incidence of FURDC, and recorded behaviors within and across groups.Construction of a Herpes Simplex Virus Type 1 Vector Expressing beta-GlucuronidaseJeffrey W. Patterson-Fortin, Srikanth Yellayi, Nigel W. FraserDepartment of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104A major obstacle to gene therapy is the difficulty in transducing all necessary cells in the target organ. This inabilityis especially apparent for gene transfer involving the brain. However, vectors created using recombinant herpes simplexvirus (HSV) are promising delivery systems for gene transfer to the brain due to the innate ability of the virus to spreadthroughout the nervous system using axonal transport. HSV-1 forms a latent neuronal infection that endures for the lifetimeof the individual. This latency is characterized by the gene expression of only latency-associated transcripts (LAT). Thisability is of interest for the development of gene therapy vectors for the brain as replacement of the LAT gene by a gene ofinterest could result in long-term expression of said gene. Mucopolysaccharidosis (MPS) VII results from the deficiency of asingle gene. This gene encodes for the lysosomal enzyme beta-glucuronidase (GUSB). Consequently, there is a failure in themetabolism of glycosaminoglycans (GAGs). These undegraded GAGs are stored in lysosomes affecting a number of organsystems, including the brain. Although rare in the human population, MPS VII is but one of over 40 identified lysosomalstorage diseases (LSDs), which collectively have a higher rate of occurrence. In this study, MPS VII is being used as amodel disease for the study of gene transfer to the brain. The goal of this study is to construct a recombinant HSV vector thatwill establish latency in the brain and secrete a feline transgene product (GUSB). The results of this study will hopefullycontribute to the understanding of widespread gene transfer to the brain. This information could be useful for continueddevelopment of recombinant HSV vectors for long-term correction of disorders affecting the brain.126