Theileria annulata: Reduced Host MMP Activity Profile of Long-Term Culture Is Transmitted as a Parasite-Encoded Trait

Adamson, Rachel; Ilhan, T.; Wilkie, Grant; Preston, Patricia M.; Brown, C.G.D.; Hall, Franklin R.

doi:10.1006/expr.1999.4469

Cited by 8 publications

(2 citation statements)

References 14 publications

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“…As it has been demonstrated that virulence and attenuation of T. annulata transformed leukocytes is a parasite encoded trait 25 , 26 , the most interesting genes are those that were down-regulated during attenuation especially the ones with a signal peptide (SP) or transmembrane domain(s) (TMDs). These are potential virulence factors as they are likely to be secreted and transferred to either schizont membrane, host cytoplasm or host cell nucleus.…”

Section: Resultsmentioning

confidence: 99%

“…For example, Darghouth et al (1996) 24 observed that virulent low passage T. annulata -transformed leukocytes often contain multiple parasite genotypes compared to attenuated lines. Interestingly, it has been shown that upon vaccination, T. annulata schizonts are transferred from vaccine cells to leukocytes of the recipient animal conferring an attenuated phenotype on them 26 . Thus, virulence of T. annulata transformed leukocytes is a parasite encoded trait but it is the infected host cell phenotype that decides on the outcome of an infection; in case of vaccination with attenuated leukocytes leading to establishment of a mild subclinical infection in vaccinated animals that protects against future field challenge.…”

Section: Introductionmentioning

confidence: 99%

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Dual RNA-seq to catalogue host and parasite gene expression changes associated with virulence of T. annulata-transformed bovine leukocytes: towards identification of attenuation biomarkers

Elati,

Tajeri,

Obara

et al. 2023

Sci Rep

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The apicomplexan parasite Theileria annulata is transmitted by Hyalomma ticks and causes an acute lymphoproliferative disease that is invariably lethal in exotic cattle breeds. The unique ability of the schizont stage of T. annulata to transform infected leukocytes to a cancer-like phenotype and the simplicity of culturing and passaging T. annulata-transformed cells in vitro have been explored for live vaccine development by attenuating the transformed cells using lengthy serial propagation in vitro. The empirical in vivo evaluation of attenuation required for each batch of long-term cultured cells is a major constraint since it is resource intensive and raises ethical issues regarding animal welfare. As yet, the molecular mechanisms underlying attenuation are not well understood. Characteristic changes in gene expression brought about by attenuation are likely to aid in the identification of novel biomarkers for attenuation. We set out to undertake a comparative transcriptome analysis of attenuated (passage 296) and virulent (passage 26) bovine leukocytes infected with a Tunisian strain of T. annulata termed Beja. RNA-seq was used to analyse gene expression profiles and the relative expression levels of selected genes were verified by real-time quantitative PCR (RT-qPCR) analysis. Among the 3538 T. annulata genes analysed, 214 were significantly differentially expressed, of which 149 genes were up-regulated and 65 down-regulated. Functional annotation of differentially expressed T. annulata genes revealed four broad categories of metabolic pathways: carbon metabolism, oxidative phosphorylation, protein processing in the endoplasmic reticulum and biosynthesis of secondary metabolites. It is interesting to note that of the top 40 genes that showed altered expression, 13 were predicted to contain a signal peptide and/or at least one transmembrane domain, suggesting possible involvement in host-parasite interaction. Of the 16,514 bovine transcripts, 284 and 277 showed up-regulated and down-regulated expression, respectively. These were assigned to functional categories relevant to cell surface, tissue morphogenesis and regulation of cell adhesion, regulation of leucocyte, lymphocyte and cell activation. The genetic alterations acquired during attenuation that we have catalogued herein, as well as the accompanying in silico functional characterization, do not only improve understanding of the attenuation process, but can also be exploited by studies aimed at identifying attenuation biomarkers across different cell lines focusing on some host and parasite genes that have been highlighted in this study, such as bovine genes (CD69, ZNF618, LPAR3, and APOL3) and parasite genes such as TA03875.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%