Interferon production by Theileria annulata‐transformed cell lines is restricted to the beta family

Abstract

Theileria are tick-transmitted protozoans causing often fatal diseases in ruminants. Theileria sporozoites immortalize and transform host cells of haematopoietic origin. Transformation is associated with profound functional alterations. For example, bovine cells infected by Theileria annulata or T. parva. constitutively produce interferon (IFN). In this study, the type and family of IFN produced by a panel of T. annulata-transformed cell lines and a T. parva-transformed cell line was investigated, using molecular probes specific for the members of the IFN-alpha, IFN-beta, IFN-gamma and IFN-omega family. T. parva-transformed cells produced IFN-gamma exclusively, whereas T. annulata-infected cells expressed type I IFN only. Analysis of mRNA expression showed that this type I IFN was confined to IFN-beta, regardless of the cellular origin of the transformed cells. When cells were exposed to double-stranded RNA (poly (I:C)) which induces IFN production in other systems, a 10-5,000 fold increase in IFN activity was noted. The amounts of IFN-beta mRNA were increased, but mRNA coding for IFN-alpha, IFN-omega or IFN-gamma was not detected. In contrast, primary macrophages, from which many of the tested lines were derived, expressed IFN-alpha, IFN-beta and IFN-omega mRNA to similar degrees when stimulated by LPS or poly (I:C). Thus, T. annulata appears to constitutively turn on IFN-beta gene transcription while silencing the genes coding for IFN-alpha and IFN-omega.

Highly syntenic and yet divergent: A tale of two Theilerias

“…The most likely function for proteins encoded by the TashAT/TpshHN families is that they operate to tailor the profile of host genes that are expressed by the infected leukocyte, possibly as cofactors to host transcription factors that are constitutively activated by the parasite. If so divergence of the TashAT/TpshHN families may explain the observed differences in genes expressed by T. annulata and T. parva infected cells (Sager et al, 1998), even though evidence suggests that both species activate the same bovine transcription factors (Dobbelaere & Kuenzi, 2004). 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 17 …”

Noncytopathic Bovine Viral Diarrhea Virus Inhibits Double-Stranded RNA-Induced Apoptosis and Interferon Synthesis

“…A temperature profile of 1 min at 94°C, 1 min at 55°C, and 1 min at 72°C after "hot start" addition of Taq polymerase was used for 30 cycles. The sequences of the IFN-specific primers used for the PCR have been described (58).…”

A Theileria annulata DNA Binding Protein Localized to the Host Cell Nucleus Alters the Phenotype of a Bovine Macrophage Cell Line

“…A primary factor in the pathology of these diseases is the generation of neoplasia by rapidly dividing transformed infected leukocytes (6). Host cell division and dedifferentiation are induced by the intracellular multinucleated macroschizont stage (18,29) and are accompanied by alterations to bovine gene expression (30). These events are dependent on a viable macroschizont, as they can be reversed by the treatment of cells with the theileriacidal drug buparvaquone (22).…”