Arenavirus-based infection as a targeted non-lytic anti-cancer virotherapy

Viruses possess the ability to effectively trigger and mediate potent immune responses within infected cells. However, while oncolytic virus therapy has shown promise as an effective therapeutic approach to target and kill cancer cells, it is unable to maintain the persistent immune response needed for complete tumour clearance, with these viruses often being eliminated before their full therapeutic potential can be achieved. Arenaviruses like lymphocytic choriomeningitis virus (LCMV) are non-cytopathic, meaning they do not kill the host cell upon infection. LCMV has been shown to preferentially replicate within cancer cells and induce and enhance a strong immune response with tumour clearance capabilities, potentially leading to tumour regression. In 'immune cold' cancer types, LCMV is a strong contender for effective viral immunotherapy. The project will advance understanding of mechanisms driving sustained immune responses from LCMV infection and explore their application in cancer treatment, starting with an investigation of virus entry and fusion receptor levels, and infection assays. The project will analyse the transcriptome of infected cancer types to identify key pathways that stimulate immune responses during LCMV replication, aiming to target mechanisms, underlying the activation or suppression of virus-mediated immune responses, that could reshape the tumour microenvironment and enhance virotherapy outcomes.