Major histocompatibility complex Class II DRB polymorphism in Maedi Visna infected Latxa sheep from the Basque Country

Maedi-Visna (MV) is a slow, progressive and fatal lymphoproliferative disease of sheep associated to infection with a lentivirus of the Retroviridae family. The virus has affinity for the monocyte-macrophage cell lineage of the lung, brain, mammary tissue and joints and animals become infected by inhalation of virus-containing aerosols and ingestion of milk containing the virus. The disease is distributed worldwide and present in over 95% of the flocks in the Basque Country in Spain. Since neither antiviral treatment or vaccination are available, disease control relies a good understanding of the pathogenesis and epidemiology of the disease and in particular of the risk factors associated with infection. Recent studies in sheep separated from their dams at birth and reared artificially, have shown a strong association between infection and the life-time infection status of the dam, suggesting there may be an important genetic component to disease susceptibility/resistance (Berriatua et al, in progress). Polymorphism at the major histocompatibility complex (MHC) has been related with disease susceptibility in other retroviral infections of animals such as Enzootic Bovine Leukosis in cattle or Caprine Arthritis-Encephalitis Virus induced arthritis in goats. As part of a large study of genetic susceptibility to viral diseases in sheep, the genetic polymorphism in the second exon of the MHC Class II DRB1 locus is being analyzed in a sample of Basque Latxa breed sheep comprising 13 half-sib families with 3 to 15 offspring. A typing assay based in Single-Strand Conformational Polymorphism (SSCP) previously developed by us is being applied. After the SSCP typing the different patterns will be sequenced, if shown to be different from previously identified. The Latxa breed may be a good model for studies of genetic disease resistance as recent studies on the DRB1 gene second exon (Jugo & Vicario, 2000) have revealed a very high frequency of an allele with the SR motif in positions 70-71 which may be of great importance in the immune response to parasites. In addition to the work currently in progress, we will extend our analysis to a larger number of families and to other MHC genes located in the Class I and Class III regions. (Texte intégral)