The patterns of diversification of FIV within different tissue compartments of infected domestic catsKahila Bar-Gal G.1, Pecon-Slattery J. 1, Tetu S.2, VandeWoude S3. and S. J.O’Brien1; 1Laboratory of Genomic Diversity, National Cancer Institute, Frederick MD; 2 Basic Research Program, SAIC - Frederick, Inc., NCI Frederick, Frederic, MD; 3Colorado State University, Fort Collins, Co (USA)Feline immunodeficiency virus (FIV) is a pathogenic lentivirus. In domestic cats, FIV infection causes immune system disease typically marked by a long asymptomatic period and progressive immune dysfunction. A dynamic interaction between the host immune system and virus causes the emergence of new mutants and selection for viral variants. The latent form of the virus may reside in different tissues for several years before the onset of full-blown infection and associated diseases. The objectives of this project are two-fold 1) to develop tissue phylogeography as a means to determine the genetic signature of viruses originating from specific tissues within an individual and 2) to track the evolutionary constraints governing viral replication and sequence diversification over time and space within an individual. We are conducting a large-scale comparative genomic sequencing project to PCR amplify, clone and sequence regions of the lentiviral genome for both proviral and circulating forms within an infected individual. We studied several individuals infected with FIV strain B. For each individual, at least 12 different tissues compartments were sampled either 11 weeks or 6.5 years post infection. The pattern of viral diversification and evolution within the different tissue compartments were studied in four gene regions: LTR, gag, pol and env. Each gene region was amplified, cloned and sequenced in duplicate in order to increase the probability of detecting most of the viral variants. The results show that there are differences in patterns of viral diversification, both among individuals inoculated with the same strain and within and between tissues of the same individual. |