Differential gene expression of virulence factors modulates infectivity of TcI Trypanosoma cruzi strains
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PROTOZOOLOGY - ORIGINAL PAPER
Differential gene expression of virulence factors modulates infectivity of TcI Trypanosoma cruzi strains Ruben D. Arroyo-Olarte 1,2 & Ignacio Martínez 1 & Eduardo Lujan 3 & Fela Mendlovic 4 & Tzvetanka Dinkova 3 & Bertha Espinoza 1 Received: 4 May 2020 / Accepted: 16 September 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Trypanosoma cruzi is the etiological agent of Chagas disease, whose clinical outcome ranges from asymptomatic individuals to chronic fatal megasyndromes. Despite being central to pathogenesis, the regulation of parasite virulence factors’ expression remains largely unknown. In this work, the relative expression of several parasite virulence factors between two TcI strains (Ninoa, low virulence and Qro, high virulence) was assessed by qRT-PCR of total and of polysome-associated mRNA, as well as by western blots. Trypomastigotes were also incubated with specific anti-sense morpholino oligonucleotides to block the translation of a selected virulence factor, calreticulin, in both strains. Ninoa trypomastigotes showed significantly lower levels of trypomastigote-decay acceleration factor, complement regulatory protein, complement C2 receptor inhibitor trispanning, and glycoproteins 82 and 90 mRNAs compared with Qro. There was a significantly lower recruitment of complement regulatory protein and complement C2 receptor inhibitor trispanning mRNAs to polysomes and higher recruitment of MASP mRNA to monosomes in Ninoa strain. Calreticulin mRNA displayed both a higher total mRNA level and recruitment to translationally active polysomes in the Ninoa strain (low virulence) than in the Qro strain (high virulence). When calreticulin was downregulated by ≈ 50% by anti-sense morpholino oligonucleotides, a significant decrease of parasite invasion in mammalian cells was found in both strains. Calreticulin downregulation, however, only increased significantly the activation of the complement system by Ninoa trypomastigotes. These results suggest a role for the regulation of virulence factors’ gene expression in the differential virulence among T. cruzi strains. Furthermore, a possible function of calreticulin in parasite invasion not related to its binding to complement factors is shown. Keywords Trypanosoma cruzi . Virulence factors . Polysome profiling . Morpholino oligonucleotides
Section Editor: Panagiotis Karanis Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00436-020-06891-1) contains supplementary material, which is available to authorized users. * Bertha Espinoza [email protected] 1
Instituto de Investigaciones Biomédicas, Departamento de Inmunología, Universidad Nacional Autónoma de México, 04510 Mexico City, Mexico
2
Present address: Departamento de Bioquímica, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, 07360 Mexico City, Mexico
3
Facultad de Química, Departamento de Bioquímica, Universidad Nacional Autónoma de México, 04510 Mexico City, Mex
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