Characterization of microRNA expression in B cells derived from Japanese black cattle naturally infected with bovine leukemia virus by deep sequencing.

Chihiro Ochiai,Toshihiro Ichijo,Kenji Murakami,Leng Dongze,To-Ichi Hirata,Kazuya Nagai,Shinji Yamada,Keisuke Tomita,Sota Kobayashi,Yuta Kudo,Yuta Naruke,Sonoko Miyauchi,Syuji Yoneyama,Yusuke Chiba,Hirokazu Hikono,Francesc Xavier Donadeu

doi:10.1371/journal.pone.0256588

Chihiro Ochiai, Toshihiro Ichijo + Show 14 more

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https://doi.org/10.1371/journal.pone.0256588

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Abstract

Bovine leukemia virus (BLV) is the causative agent of enzootic bovine leukosis (EBL), a malignant B cell lymphoma. However, the mechanisms of BLV-associated lymphomagenesis remain poorly understood. Here, after deep sequencing, we performed comparative analyses of B cell microRNAs (miRNAs) in cattle infected with BLV and those without BLV. In BLV-infected cattle, BLV-derived miRNAs (blv-miRNAs) accounted for 38% of all miRNAs in B cells. Four of these blv-miRNAs (blv-miR-B1-5p, blv-miR-B2-5p, blv-miR-B4-3p, and blv-miR-B5-5p) had highly significant positive correlations with BLV proviral load (PVL). The read counts of 90 host-derived miRNAs (bta-miRNAs) were significantly down-regulated in BLV-infected cattle compared to those in uninfected cattle. Only bta-miR-375 had a positive correlation with PVL in BLV-infected cattle and was highly expressed in the B cell lymphoma tissue of EBL cattle. There were a few bta-miRNAs that correlated with BLV tax/rex gene expression; however, BLV AS1 expression had a significant negative correlation with many of the down-regulated bta-miRNAs that are important for tumor development and/or tumor suppression. These results suggest that BLV promotes lymphomagenesis via AS1 and blv-miRNAs, rather than tax/rex, by down-regulating the expression of bta-miRNAs that have a tumor-suppressing function, and this downregulation is linked to increased PVL.

Highlights

Bovine leukemia virus (BLV) is an RNA virus belonging to the genus Delta retrovirus, family Retroviridae, and is closely related to human T-lymphotropic virus-1 (HTLV-1) [1]
The read counts of four blv-miRNAs had a strong positive correlation with BLV proviral load (PVL) (correlation coefficient (r) > 0.7, p < 0.05, Fig 2A–2D)
Ten BLV provirus-derived microRNAs were detected in B cells derived from BLV-infected cattle, and these blv-miRNAs accounted for 38% of all detected miRNAs

Summary

Introduction

Bovine leukemia virus (BLV) is an RNA virus belonging to the genus Delta retrovirus, family Retroviridae, and is closely related to human T-lymphotropic virus-1 (HTLV-1) [1]. BLV is the causative agent of enzootic bovine leukosis (EBL), a malignant B cell lymphoma [2, 3]. BLV infection is prevalent worldwide, causing large economic losses in the cattle industry. In Japan, a nationwide survey (2010–2011) of BLV revealed that the prevalence was 28.7% and 40.7% in beef breeding and dairy cattle, respectively [4]. The following countries and regions around the world have reported moderate increases in BLV, with prevalences of 2.3% in Turkey [9], 41.3% in Iran [10], 3.9% in Mongolia [11], 9.7% in the Philippines [12], 21.5% in Egypt [13], 12.6% in South Africa [14], and 62% in Colombia [15]. BLV infection has severely damaged the Japanese beef industry, which is well known for its production of highly expensive Wagyu [17]

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