RESUMO
Utilisation of RNA-binding proteins (RBPs) is an important aspect of post-transcriptional regulation of viral RNA. Viruses such as influenza A viruses (IAV) interact with RBPs to regulate processes including splicing, nuclear export and trafficking, while also encoding RBPs within their genomes, such as NP and NS1. But with almost 1000 RBPs encoded within the human genome it is still unclear what role, if any, many of these proteins play during viral replication. Using the RNA interactome capture (RIC) technique, we isolated RBPs from IAV infected cells to unravel the RBPome of mRNAs from IAV infected human cells. This led to the identification of one particular RBP, MKRN2, that associates with and positively regulates IAV mRNA. Through further validation, we determined that MKRN2 is involved in the nuclear-cytoplasmic trafficking of IAV mRNA potentially through an association with the RNA export mediator GLE1. In the absence of MKRN2, IAV mRNAs accumulate in the nucleus of infected cells, which may lead to their degradation by the nuclear RNA exosome complex. MKRN2, therefore, appears to be required for the efficient nuclear export of IAV mRNAs in human cells.
Assuntos
Vírus da Influenza A , Influenza Humana , RNA Mensageiro , RNA Viral , Proteínas de Ligação a RNA , Animais , Humanos , Transporte Ativo do Núcleo Celular , Núcleo Celular/metabolismo , Núcleo Celular/virologia , Vírus da Influenza A/genética , Influenza Humana/metabolismo , Influenza Humana/virologia , Influenza Humana/genética , Transporte de RNA , RNA Mensageiro/metabolismo , RNA Mensageiro/genética , RNA Viral/metabolismo , RNA Viral/genética , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genética , Replicação ViralRESUMO
Bovine respiratory disease complex (BRDC) is a multifactorial disease of cattle which presents as bacterial and viral pneumonia. The causative agents of BRDC work in synergy to suppress the host immune response and increase the colonisation of the lower respiratory tracts by pathogenic bacteria. Environmental stress and/or viral infection predispose cattle to secondary bacterial infections via suppression of key innate and adaptive immune mechanisms. This allows bacteria to descend the respiratory tract unchallenged. BRDC is the costliest disease among feedlot cattle, and whilst vaccines exist for individual pathogens, there is still a lack of evidence for the efficacy of these vaccines and uncertainty surrounding the optimum timing of delivery. This review outlines the immunosuppressive actions of the individual pathogens involved in BRDC and highlights the key issues in the development of vaccinations against them.