Novel single nucleotide polymorphisms in the bovine leukemia virus genome are associated with proviral load and affect the expression profile of viral non-coding transcripts
Novel single nucleotide polymorphisms in the bovine leukemia virus genome are associated with proviral load and affect the expression profile of viral non-coding transcripts
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DOI：
10.1016/j.vetmic.2021.109200
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发表时间：
2021-08-06
影响因子：
3.3
通讯作者：
Hatama, Shinichi
中科院分区：
文献类型：
--
作者：
Andoh, Kiyohiko;Akagami, Masataka;Hatama, Shinichi
牛白血病病毒（BLV）感染牛B细胞并引起恶性淋巴瘤，给畜牧业造成严重的经济损失。为了控制BLV的传播，一些研究试图阐明BLV致病的分子机制，但其机制的细节仍然是谜。目前，病毒非编码RNA作为BLV发病机制的新参与者引起了人们的注意，因为这些转录物可以逃避宿主免疫应答并且在潜伏感染中持续表达。病毒非编码RNA之一AS 1编码于BLV基因组的反义链中，并由两种亚型AS 1-L和AS 1-S组成。尽管AS 1的功能尚不清楚，但由于AS 1 RNA在肿瘤组织中持续表达，可能也具有一定的作用。在本研究中，我们确定了新的单核苷酸多态性（SNPs）位于AS 1编码区，并表明与BLV感染的个体与轻微的SNPs表现出低前病毒负荷。为了评估所鉴定的SNP的效果，我们用这些SNP构建了感染性克隆，发现它们的引入影响了AS 1 RNA的表达谱;与野生型相比，AS 1-L同种型的量增加，尽管AS 1 RNA的总量保持不变。预测分析还表明，SNPs的引入改变了AS 1 RNA的二级结构。这些结果部分解释了BLV体内扩增与AS 1表达谱之间的关系，但需要进一步分析。
Bovine leukemia virus (BLV) infects bovine B-cells and causes malignant lymphoma, resulting in severe economic losses in the livestock industry. To control the spread of BLV, several studies have attempted to clarify the molecular mechanisms of BLV pathogenesis, but the details of the mechanism are still enigmatic. Currently, viral non-coding RNAs are attracting attention as a novel player for BLV pathogenesis because these transcripts can evade the host immune response and are persistently expressed in latent infection. One of the viral non-coding RNA, AS1, is encoded in the antisense strand of the BLV genome and consists of two isoforms, AS1-L and AS1-S. Although the function of the AS1 is still unknown, the AS1 RNA might also have some roles because it keeps expressing in tumor tissues. In the present study, we identified novel single nucleotide polymorphisms (SNPs) located in the AS1 coding region and indicated that individuals infected with BLV with minor SNPs showed low proviral load. To evaluate the effect of identified SNPs, we constructed infectious clones with these SNPs and found that their introduction affected the expression profile of AS1 RNA; the amount of AS1-L isoform increased compared with the wild type, although the total amount of AS1 RNA remained unchanged. Prediction analysis also suggested that the introduction of SNPs changed the secondary structure of AS1 RNA. These results explain part of the relationship between BLV expansion in vivo and the expression profile of AS1, although further analysis is required.