Trypanosoma vivax infection in sheep: Different patterns of virulence and pathogenicity associated with differentially expressed proteomes

Abstract

Cattle trypanosomosis caused by Trypanosoma vivax is a widely distributed disease in Africa and Latin America. It causes significant losses in the livestock industry and is characterized by fluctuating parasitemia, anemia, fever, lethargy, and weight loss. In this study we evaluated the virulence (capacity to multiply inside the host and to modulate the host response) and pathogenicity (ability to produce disease and/or mortality) patterns of two T. vivax strains (TvMT1 and TvLIEM176) in experimentally-infected sheep and determined the proteins differentially expressed in the proteomes of these two strains. Hematological and clinical parameters were monitored in experimentally-infected versus non-infected sheep for 60 days. All the infected animals developed discernable parasitemia at 3 days post-infection (dpi), and the first parasitemia peak was observed at 6 dpi. The maximum average value of parasitemia was 1.3 × 10⁷ (95% CI, 7.9 × 10⁵-2 × 10⁸) parasites/ml in TvLIEM176-infected animals, and 2.5 × 10⁶ (95% CI, 1.6 × 10⁵-4 × 10⁷) parasites/ml in TvMT1-infected ones. Anemia and clinical manifestations were more severe in the animals infected by TvMT1 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 T. vivax strains: TvLIEM176 showed high virulence and moderate 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 T. vivax infections.

Keywords: Biomarkers; Pathogenicity; Proteomics; Trypanosoma vivax; Virulence.

Fig. 1

Hematological analysis of non-infected and experimentally-infected sheep with Trypanosoma vivax strains TvMT1 and TvLIEM176. Adjusted mean values and 95% confidence intervals of parasitemia (log₁₀ parasites/ml, panel A), PCV (%, panel B), hemoglobin (g/dl, panel C), and WBC counts (cells x 10³/μl, panel D) during infection. Each group consisted of three sheep.

Fig. 2

Adjusted mean absolute values and 95% confidence intervals for blood concentrations of lymphocytes (cells x 10³/μl, panel A), neutrophils (cells x 10³/μl, panel B), monocytes (cells x 10²/μl, panel C), and eosinophils (cells x 10³/μl, panel D) of non-infected and experimentally-infected sheep with Trypanosoma vivax strains TvMT1 and TvLIEM176. Each group consisted of three sheep.

Fig. 3

Vital signs of non-infected and experimentally-infected sheep with Trypanosoma vivax strains TvMT1 and TvLIEM176. Adjusted mean values and 95% confidence intervals of body temperature (°C, panel A), heart rate (beats/min, panel B), and respiratory rate (breaths/min, panel C) during infection. Each group consisted of three sheep.

Fig. 4

Two-dimensional synthetic image of differential in-gel electrophoresis gels displaying differentially expressed protein spots identified in the proteome of Trypanosoma vivax TvMT1 and TvLIEM176 strains.