病毒利用多种策略引起潜伏感染并逃避宿主免疫反应。长非编码RNA（lncRNA）是一类通过与RNA结合蛋白相互作用调节多种细胞功能的非蛋白编码RNA，在某些病毒（如疱疹病毒和逆转录病毒）的潜伏期中起着重要作用，因为它不具有抗原性。牛白血病病毒（BLV）属于逆转录病毒科，编码了BLV衍生的lncRNA AS1-S，该lncRNA是潜伏感染细胞中的主要转录本。我们通过RNA-蛋白拉取实验确定了位于细胞核中的RNA结合蛋白牛杂核糖核蛋白M（hnRNPM）与AS1-S的结合伴侣关系。使用重组hnRNPM突变体的拉取实验表明，位于牛hnRNPM的N末端区域的RNA识别结构域（RRMs）1和2对与AS1-S的结合负责。此外，RNA免疫沉淀（RIP）实验结果显示，在MDBK细胞中AS1-S的表达增加了与牛hnRNPM共同免疫沉淀的mRNA数量。这些结果提示，AS1-S可能改变hnRNPM与宿主mRNA相互作用，可能干扰核内mRNA成熟的初始阶段的细胞功能。由于大多数与hnRNPM结合增加的已鉴定mRNA与KEGG术语“癌症途径”相关，AS1-S可能影响BLV感染细胞的增殖和扩展，并促进肿瘤进展。意义BLV感染牛B细胞并引起恶性淋巴瘤，这是对畜牧业的严重影响。由于发病率低且潜伏期长，淋巴瘤发展的分子机制仍然不清楚。最近在BLV基因组中发现了几种非编码RNA（ncRNA），如miRNA和lncRNA，并且BLV发病机制与这些ncRNA之间的关系备受关注。然而，这些转录本的大部分分子功能仍未鉴定。据我们所知，这是首次描述BLV衍生的lncRNA AS1-S分子功能的报告。这里报道的发现揭示了BLV发病机制的一种新机制，对BLV研究和逆转录病毒的比较研究都提供了重要见解。

Viruses utilize several strategies to cause latent infection and evade host immune responses. Long non-coding RNA (lncRNA), a class of non-protein-encoding RNA that regulates various cellular functions by interacting with RNA-binding proteins, plays important roles for viral latency in several viruses, such as herpesviruses and retroviruses, due to its lack of antigenicity. Bovine leukemia virus (BLV), which belongs to the family Retroviridae, encodes the BLV-derived lncRNA AS1-S, which is a major transcript expressed in latently infected cells. We herein identified bovine heterogeneous nuclear ribonucleoprotein M (hnRNPM), an RNA-binding protein located in the nucleus, as the binding partner of AS1-S using an RNA-protein pull-down assay. The pull-down assay using recombinant hnRNPM mutants showed that RNA recognition motifs (RRMs) 1 and 2, located in the N-terminal region of bovine hnRNPM, were responsible for the binding to AS1-S. Furthermore, RNA immunoprecipitation (RIP) assay results showed that the expression of AS1-S increased the number of mRNAs that co-immunoprecipitated with bovine hnRNPM in MDBK cells. These results suggested that AS1-S could alter the interaction between hnRNPM and host mRNAs, potentially interfering with cellular functions during the initial phase of mRNA maturation in the nucleus. Since most of the identified mRNAs that exhibited increased binding to hnRNPM were correlated with the KEGG term "Pathways in cancer," AS1-S might affect the proliferation and expansion of BLV-infected cells and contribute to tumor progression. IMPORTANCE BLV infects bovine B cells and causes malignant lymphoma, a disease that greatly affects the livestock industry. Due to its low incidence and long latent period, the molecular mechanisms underlying the progression of lymphoma remain enigmatic. Several non-coding RNAs (ncRNAs), such as miRNA and lncRNA, have recently been discovered in the BLV genome, and the relationship between BLV pathogenesis and these ncRNAs is attracting attention. However, most of the molecular functions of these transcripts remain unidentified. To the best of our knowledge, this is the first report describing a molecular function for the BLV-derived lncRNA AS1-S. The findings reported herein reveal a novel mechanism underlying BLV pathogenesis that could provide important insights for not only BLV research but also comparative studies of retroviruses.