Bovine leukemia virus (BLV) is one of the pathogens causing major economic losses in livestock industry. BLV causes lymphoma, a cancer of white blood cells in cattle. National Agriculture and Food Research Organization (NARO) has discovered that the "non protein coding RNA" (non-coding RNA: ncRNA) expressed by BLV, binds to a protein in the nucleus of host cells and alters its RNA-binding capacity. This ncRNA is one of the few viral factors expressed in tumor cells and may contribute to the development of lymphoma. This is the first report in the world showing that the ncRNA expressed by BLV binds directly to the host protein and interferes with its functions.
Overview
In recent years, it has become clear that "non protein coding RNA"(non-coding RNA: ncRNA) contribute to the development of diseases such as cancer. Hence these findings are attracting attention as a new approach for elucidating pathological conditions.
Bovine leukemia virus (BLV), which is the cause of bovine infectious disease "Enzootic bovine leukosis", is also known to express ncRNAs, and it is suspected that the ncRNAs of BLV is associated with lymphoma development. BLV infects B cells, one of the immune cells, causes lifelong infection in infected cattle and then causes lymphoma in some individuals. The development of effective vaccines and treatments is urgently needed because of the economic damage caused by the disposal of cattle with lymphoma. However, the precise mechanism by which BLV causes lymphoma has not yet been elucidated, and effective prevention and treatment methods have yet to be realized. Therefore, elucidation of the ncRNA function of BLV is expected to greatly contribute to solving this problem.
NARO has conducted a detailed analysis of the AS1-S gene, one of the genes of BLV whose functions are unknown. As a result, NARO discovered ncRNA (AS1-S RNA) expressed from the AS1-S gene binds to a protein called heterogeneous nuclear ribonucleoprotein M (hnRNPM) in the nucleus of the host cell and alters the binding between hnRNPM and host RNAs. hnRNPM is a protein that regulates various cellular functions by processing RNA in the cell nucleus. AS1-S RNA may cause abnormal proliferation of infected cells by inhibiting the processing and regulation of host RNA by hnRNPM. This discovery is the first report in the world in which a part of the molecular function of ncRNA expressed by BLV was clarified. This is believed to be a major clue to deepen the understanding of the mechanism by which virus cause disease, as basic knowledge that will contribute to the elucidation of the mechanism of lymphoma development in cattle and the development of the control method.
Publication
The bovine leukemia virus-derived long non-coding RNA AS1-S binds to bovine hnRNPM and alters the interaction between hnRNPM and host mRNAs.Kiyohiko Andoh, Asami Nishimori, Yuichi Matsuura. Microbiology Spectrum, doi.org/10.1128/spectrum.00855-23.
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