The exploration of host-parasite interactions could lead to the development of improved diagnostic tools, new drugs, and/or vaccine strategies. Vaccine control of trypanosomosis is strongly limited by the complexity of the parasites antigenic repertoire. strain than in those infected by TvLIEM176. In the proteomic analysis, a total of 29 proteins were identified, of which 14 exhibited significant differences in their expression levels between strains. Proteins with higher expression in TvLIEM176 were: alpha tubulin, beta tubulin, arginine kinase, glucose-regulated protein 78, paraflagellar protein 3, and T-complex protein 1 subunit theta. Proteins with higher expression in TvMT1 were: chaperonin HSP60, T-complex protein 1 subunit alpha, heat shock protein 70, pyruvate kinase, glycerol kinase, inosine-5′-monophosphate dehydrogenase, 73?kDa paraflagellar rod protein, and vacuolar ATP synthase. There was a difference in the virulence and pathogenicity between the strains: TvLIEM176 showed high virulence and moderate DKFZp686G052 pathogenicity, whereas TvMT1 showed low virulence and high pathogenicity. The proteins identified in this study are discussed for their potential involvement in strains virulence and pathogenicity, to be further defined as biomarkers of severity in infections. and in Africa (Auty et al., 2015, Chamond et al., 2010). In Latin America, bovine trypanosomosis is caused by and (Surez et al., 2009, Toro et al., 1980). It has been proposed that the severity of the disease depends on parasite strain, endemicity and host species (Auty et al., 2015, Batista et al., 2007, Morrison et al., 2016). However, the discrete roles the host, the parasite, and their relationships at the molecular level play in the different clinical disease presentations are poorly understood. The exploration of host-parasite interactions could lead to the development of improved diagnostic tools, new drugs, and/or vaccine strategies. Vaccine control of trypanosomosis is strongly limited by WWL70 the complexity of the parasites antigenic repertoire. A further challenge is that knowledge about trypanosome antigenic variation comes primarily from the model where variant surface glycoprotein (VSG) is highly immunogenic. expression of the VSG repertoire differs from that of in different hosts have demonstrated that parasite and host genotypes have a major impact on infection progression (de Gee et al., 1979, 1981, 1982). Differences have been found in the susceptibility of inbred mouse strains to infections with isolates of medium or low virulence; however, no resistant model has been identified (de Gee et al., 1982). WWL70 Although mouse models have been useful to understand the course and disease progression in strains in experimentally-infected sheep, and identify the differentially expressed proteins between them with a combination of 2-D differential in-gel electrophoresis (DIGE) and mass spectrometry (MS). 2.?Materials and methods 2.1. Parasites The strains used in the experiments, TvLIEM176 (a gift from Dr. Laura Moron and Dr. Glenda Moreno, Los Andes University) and TvMT1, were obtained from naturally-infected cattle from different locations in Venezuela: TvLIEM176 from Trujillo State (Western region) and TvMT1 from Monagas State (Eastern region) as previously described (Gmez-Pi?eres et al., 2014). Diagnosis of infection was performed by microhematocrit analysis (Woo, 1969) and polymerase chain reaction (PCR) as described (Masake et al., 1997). Blood was collected in tubes containing 1?mg/ml of ethylenediaminetetracetic acid (EDTA), mixed with 10% glycerol in 20?mM phosphate buffered saline (PBS) pH 7.2 containing 1% glucose (PBSG) and frozen in liquid nitrogen (Gmez-Pi?eres et al., 2009, Ndao et al., 2004). 2.2. Experimental infections Nine adult Barbados Blackbelly sheep, eighteen months old, weighing 20?kg, and negative for infection (determined by ELISA and PCR tests) were purchased from a local market. Tests for gastrointestinal parasites (fecal flotation test) and liver fluke (fecal sedimentation test) were performed at time of purchase. Three animals were positive for gastrointestinal nematodes. Ivermectin at a dose of WWL70 0.2?mg/kg was administered to all animals. Two weeks before and during experimental infection, all animals were maintained under veterinary supervision in order to monitor animal health and welfare at Centro Experimental de Produccin Animal (CEPA, College of Veterinary Medicine, University of Zulia) in fly-proof pens. Three sheep were inoculated intravenously with each isolate (106 parasites/animal) and three were used as control. After 60-day infection period,.