Ottawa, ON -- (SBWIRE) -- 02/19/2020 -- Studies have shown that for several viruses, multiple viral genes are involved in the regulation of the innate immune response that is mediated by the interferon response. This response is a major determinant of the pathogenicity of viruses; it also contributes to the ability of certain viruses to distinguish between cancer cells and parental cells. Some researchers have stated that an in-depth understanding of this determinant is quintessential to the conduction of epidemiological surveillance as well as the successful optimization and selection of appropriate viral strains for the treatment of different types of cancer.
In view of this, virologists have begun to explore the possible use of oncolytic viruses (such as mammalian orthoreovirus) for the treatment of cancer. Mammalian orthoreovirus is considered to be an appropriate oncolytic virus for cancer treatment because it is non-pathogenic to humans. However, previous studies have indicated the possible emergence of novel mammalian orthoreovirus strains that may be pathogenic to humans. Moreover, interferon-mediated immune response may be involved in the emergence of pathogenic viral strains. These possibilities necessitate the conduction of further research studies to fully understand the viral determinants that regulate the induction of interferon response and the susceptibility of different viruses to this response.
In a recent publication featured in Medicine Innovates and selected as a key scientific article, scientists at University of Montreal Delphine Lanoie, Stéphanie Côté, Emmanuelle Degeorges and led by professor Guy Lemay from the Department of Microbiology demonstrated that the single mutation of the S1 gene is solely responsible for increased interferon sensitivity in a mammalian orthoreovirus mutant previously selected in Vero cells that are deficient in the interferon response. The authors used a combination of whole-genome sequencing and reverse genetics techniques to identify the unique mutation that occurred in the S1 gene that resulted in increased interferon sensitivity in this virus compared to its parental wild-type counterpart.
The research team observed that the rescued Vero-cell-adapted virus (VeroAV) induced a similarly low amount of interferon as the control rescued wild-type virus. However, the rescued VeroAV was a hundred fold more sensitive compared to the wild-type.
The researchers also reported that introducing the VeroAV M1, M2 or M3 gene into the wild-type background from which the VeroAV was initially derived had no effect on the interferon sensitivity. Whereas, the sole introduction of VeroAV S1 and M2 resulted in a virus that is as sensitive as the rescued VeroAV. The other five viral genes were identical between the two viruses. Moreover, they observed that the substitution of Q78P of ?1 (N59H in ?1s) in the S1 gene was required to fully reconstitute the interferon sensitivity of the rescued VeroAV, while complete knockout of ?1s expression also resulted in interferon sensitivity.
The findings of Professor Guy Lemay and his research team provided compelling evidence that the mutation of the S1 gene in the rescued VeroAV is solely responsible for increased interferon sensitivity in the virus. They also suggest a novel function of ?1s in the control of interferon sensitivity. These findings are important and could lead to further studies on the applications of viruses as potential oncolytic agents and the development of better adapted viruses as effective treatment solutions to different types of cancer.
The story has been featured first at Medicine Innovates:
https://medicineinnovates.com/reovirus-one-amino-acid-change-everything/
About Medicine Innovates
Medicine Innovates is the leading source of trustworthy and timely medical research news. It continues to feature the very best in research paper in medicine breakthroughs, with articles that consistently rank among the most cited in the world. Medicine Innovates select research papers that are most influential in their biomedical field and that will significantly advance scientific understanding. Selected papers tend to present novel and broadly important data, or concepts.
Contact
Dr. Robert Miller
Medicine Innovates
https://medicineinnovates.com