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Oncolytic virotherapy is an emerging treatment option for numerous cancers, with several virus families currently being evaluated in clinical trials. More specifically, vaccine-strain measles virus has arisen as a promising candidate for the treatment of different tumour types in several early clinical trials. Replicating viruses, and especially RNA viruses without proofreading polymerases, can rapidly adapt to varying environments by selecting quasispecies with advantageous genetic mutations. Subsequently, these genetic alterations could potentially weaken the safety profile of virotherapy. In this study, we demonstrate that, following an extended period of virus replication in producer or cancer cell lines, the quasispecies consensus sequence of vaccine strain-derived measles virus accrues a remarkably small number of mutations throughout the nonsegmented negative-stranded RNA genome. Interestingly, we detected a nonrandom distribution of genetic alterations within the genome, with an overall decreasing frequency of mutations from the 3' genome start to its 5' end. Comparing the serially passaged viruses to the parental virus on producer cells, we found that the acquired consensus mutations did not drastically change viral replication kinetics or cytolytic potency. Collectively, our data corroborate the genomic stability and excellent safety profile of oncolytic measles virus, thus supporting its continued development and clinical translation as a promising viro-immunotherapeutic.
This article was published in the following journal.
Name: The Journal of general virology
To map genomic diversity of Measles virus (MeV) isolates collected during 2009-2017 from ten states of India.
Measles virus is highly infectious and remains a leading cause of vaccine preventable deaths in children. Neutralizing antibody responses elicited by measles virus infection or immunization are a sero...
Measles and rubella are highly contagious viral diseases transmitted via respiratory secretions and aerosolized droplets. Thailand has implemented universal vaccination against measles using the monov...
The measles virus epithelial receptor has recently been identified by two teams. It is nectin-4, also named Polio Virus Receptor Like 4. Nectin-4 is a component of the adherens junctions in certain e...
Measles is a highly infectious viral illnesses and is one of the world most contagious diseases that can affect in all people if they have not been vaccinated or have not had it before. Before measles...
This is a two arm Phase I study within the Pacific Pediatric Neuro-Oncology Consortium (PNOC). This study will look to determine the safety and recommended phase 2 dose of the modified ...
Investigators aim to use comparative exome and/or genome sequencing to discover causative molecular lesions for phenotypes hypothesized to be caused by somatic mutations. For this study, i...
This study will seek to determine if rapid genomic sequencing improves outcomes for acutely ill infants. The investigator will enroll up to 1,000 acutely ill infants in a prospective, rand...
This is an immunogenicity study evaluating the development of the immune response of healthy infants following primary vaccination with Attenuvax at 6 or 9 months of age compared with resp...
The purpose of this trial is to study the safety and immune response to measles, mumps, and rubella in children who were vaccinated with an investigational measles-mumps-rubella live vacci...
A live attenuated virus vaccine of chick embryo origin, used for routine immunization of children and for immunization of adolescents and adults who have not had measles or been immunized with live measles vaccine and have no serum antibodies against measles. Children are usually immunized with measles-mumps-rubella combination vaccine. (From Dorland, 28th ed)
The type species of MORBILLIVIRUS and the cause of the highly infectious human disease MEASLES, which affects mostly children.
A defective variant of MEASLES VIRUS that has been isolated from the brain tissue of patients with subacute sclerosing panencephalitis.
A rare, slowly progressive encephalitis caused by chronic infection with the MEASLES VIRUS. The condition occurs primarily in children and young adults, approximately 2-8 years after the initial infection. A gradual decline in intellectual abilities and behavioral alterations are followed by progressive MYOCLONUS; MUSCLE SPASTICITY; SEIZURES; DEMENTIA; autonomic dysfunction; and ATAXIA. DEATH usually occurs 1-3 years after disease onset. Pathologic features include perivascular cuffing, eosinophilic cytoplasmic inclusions, neurophagia, and fibrous gliosis. It is caused by the SSPE virus, which is a defective variant of MEASLES VIRUS. (From Adams et al., Principles of Neurology, 6th ed, pp767-8)
A species of ALPHAVIRUS causing a measles-like acute febrile rash illness. It is closely related to the Chikungunya virus and Igbo Ora viruses.
DNA sequencing is the process of determining the precise order of nucleotides within a DNA molecule. During DNA sequencing, the bases of a small fragment of DNA are sequentially identified from signals emitted as each fragment is re-synthesized from a ...
Measles (morbilli, rubeola) is a highly infectious viral illness that can be very unpleasant and can sometimes lead to serious complications. The initial symptoms of measles develop around 10 days after initial infection: a high temperature (...