Unravelling the interplay between influenza A virus and transfer RNA-modifying enzymes

• Autor(a) principal: Nunes, Alexandre Miguel Manana
• Data de Publicação: 2019
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10773/28431
• topic: Influenza A Virus (IAV); Virus Infection; Proteostasis; Virus-Host Interactions; Transfer RNA (tRNA); tRNA Modifications; tRNA-Modifying Enzymes

Viruses, such as the influenza A virus (IAV), are the causative agent for most of the annual respiratory epidemics in humans, and they take control of the host cell machinery and establish precise interactions with cellular components in order to propagate. The fundamental reason why viruses need living cells to multiply, is because they lack key elements that are needed for replication such as transfer ribonucleic acids (tRNAs). IAV has been shown to specifically manipulate the host-cell tRNA population to enable the efficient translation of viral proteins. tRNAs are modified, post-transcriptionally, by tRNA-modifying enzymes (TMEs) to ensure their stability and efficient translation. The majority of these modifications occurs at the wobble position, located at the anticodon loop, although they may also happen in other areas of the tRNA structure. In this study we aimed to determine whether IAV infection leads to changes in the expression of the genes that code for the TMEs. Our results demonstrated that particular genes (ELP1, ELP3, ELP6, ALKBH8 and TRMT2A) were overexpressed two hours post-infection while no striking changes were detected in other time points. We also aimed to determine whether the lack of ELP3 would influence the viral particle production by the infected cells. Using ELP3 knockout cells, our preliminary results show that the absence of this TME notably reduces viral production, suggesting a relevant role for ELP3 on the IAV life-cycle.