Alternative splicing in human tumour viruses: a therapeutic target?
Persistent infection with cancer risk-related viruses leads to molecular, cellular and immune response changes in host organisms that in some cases direct cellular transformation. Alternative splicing is a conserved cellular process that increases the coding complexity of genomes at the pre-mRNA processing stage. Human and other animal tumour viruses use alternative splicing as a process to maximize their transcriptomes and proteomes. Medical therapeutics to clear persistent viral infections are still limited. However, specific lessons learned in some viruses [e.g. HIV and HCV (hepatitis C virus)] suggest that drug-directed inhibition of alternative splicing could be useful for this purpose. The present review describes the basic mechanisms of constitutive and alternative splicing in a cellular context and known splicing patterns and the mechanisms by which these might be achieved for the major human infective tumour viruses. The roles of splicing-related proteins expressed by these viruses in cellular and viral gene regulation are explored. Moreover, we discuss some currently available drugs targeting SR (serine/arginine-rich) proteins that are the main regulators of constitutive and alternative splicing, and their potential use in treatment for so-called persistent viral infections.
Centre for Virus Research, Institute of Infection Immunity and Inflammation, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow G61 1QH, Scotland, U.K.
Hegel R
HR
Hernandez-Lopez
Sheila V
SV
Graham
D017398:Alternative Splicing; D015967:Gene Expression Regulation, Viral; D006801:Humans; D009369:Neoplasms / Q000209:etiology* / Q000628:therapy*; D009858:Oncogenic Viruses / Q000472:pathogenicity*; D014412:Tumor Virus Infections