Abstract

Bovine Leukemia Virus (BLV) is an established model for studying retroviral infections, in particular the infection by the human T-cell leukemia type 1 (HTLV-1) virus. Here, we quantified gene expression of several BLV-related genes: effector protein of T and NK-killer cells NK-lysin (Nklys), reverse BLV transcriptase pol, BLV receptor (blvr), and also key enzymes of the microRNA maturation, Dicer (dc1) and Argonaut (ago2). The differences in the expression of the above genes were compared between five groups: (1) BLV infected cows with high and (2) low lymphocyte count, (3) with and (4) without BLV microRNA expressions, and (5) cows without BLV infections (control group). As compared to control, infected cows with high lymphocyte count and BLV microRNA expression had significantly decreased Nklys gene expression and increased dc1 and ago2 gene expressions. Few infected animals without pol gene expression nevertheless transcribed BLV microRNA, while others with pol gene expression didn't transcribe BLV microRNA. Notably, Pol expression significantly (P < 0.05) correlated with dc1 expression. For infected animals, there were no direct correlations between the number of leukocytes and pol, Nklys, and BLV microRNA gene expressions. Blvr gene expression is typical for juvenile lymphocytes and decreases during terminal differentiation. Our data suggest that BLV infects primarily juvenile lymphocytes, which further divide into two groups. One group expresses BLV DNA and another one expressed BLV microRNA that decreases host immune response against cells, expressing BLV proteins. It is suspected that regulatory microRNAs play a significant role in the bovine leukemia infections, yet the precise mechanisms and targets of the microRNAs remain poorly defined. Vaccines that are currently in use have a low response rate. Understanding of microRNA regulatory mechanisms and targets would allow to develop more effective vaccines for retroviral infections.

Highlights

  • Retroviruses are the main source of infections in humans and farm animals [1]

  • It is important to know if there is a connection between proviral Bovine Leukemia Virus (BLV) DNA expression, BLV microRNA expressions, leukoses, and the suppression of the host immune system, because BLV microRNA participates in pathogenesis induced by this retrovirus [14]

  • In this work, we evaluate correlations between leukocytosis, expression of reverse transcriptase BLV pol, NK-lysin, BLV microRNA, genes dc1 and ago2, as well as the gene encoding cellular receptor for BLV

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Summary

INTRODUCTION

Retroviruses are the main source of infections in humans and farm animals [1]. During the course of evolution, retroviruses acquired the ability to suppress host immunity. The authors assume that transcriptional activation of BLV micro-RNA cluster in primary tumors and pre-leukemic clones is caused by negative selection against cell clones expressing BLV proteins provided by host immune system. There is an evidence for counteraction between proviral BLV DNA expression and microRNA expression as a result of host immune system selection pressure against cellular clones expressing BLV proteins. It could indicate that the major BLV-induced infection event is the suppression of the host immune system. It is important to know if there is a connection between proviral BLV DNA expression, BLV microRNA expressions, leukoses, and the suppression of the host immune system, because BLV microRNA participates in pathogenesis induced by this retrovirus [14]. In this work, we evaluate correlations between leukocytosis, expression of reverse transcriptase BLV pol, NK-lysin (that marks the activity of T and NK killers), BLV microRNA, genes dc and ago (their products participate in microRNA maturation), as well as the gene encoding cellular receptor for BLV (blvr)

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