The Secret Viral Highway: Hijacking Tunnelling Nanotubes to Hijack Viral Transmission

Abstract

First discovered in 2004, tunnelling nanotubes (TNTs) are fascinating actin-rich subcellular tubular structures that connect distant cells and are crucial for cell-to-cell communication. While they’ve typically been shown to be involved in the transport of cellular cargo between cells, a growing amount of evidence has suggested that they also play a key role in many pathologies including viral pathogenesis. With evidence of their activity being involved in the pathogenesis of many viruses of global threat including HIV, IAV, SARS-CoV-2 and Ebola, TNTs have been shown to mediate the transport of infectious virions and viral proteins into nearby healthy cells in a way that allows infection to spread while escaping immune detection as well as many antiviral therapies. With it being a major route of intracellular viral spread and immune evasion, TNTs are an excellent novel host-directed strategic target for antiviral therapeutics. TNTs have also been shown to play key roles in cancer and neurodegenerative disease pathology which often can coexist with viral infections or be downstream effects of it. Thus, targeting TNTs can provide the additional benefit of addressing comorbidities while also preventing the chances of these diseases developing as a result of infection. This paper will investigate how viruses can hijack host cellular mechanisms used in TNT formation so that they can use them for their spread. It will also explore which of these pathways will be most effective to target with the least cellular toxicity for the development of host-directed antiviral therapeutics.