A large group of vector-borne (like Dengue and Zika) and respiratory (including Influenza and COVID-19) viruses ravaging global human health are RNA viruses. These viruses, distinct in using RNA as their core genetic material, also trigger some unique responses in an infected cell, especially as far as stress pathways and homeostatic responses are concerned.
Since the endoplasmic reticulum (ER) is the principal seat of viral translation and replication and, to some extent, maturation, the ensuing hijacking of the host cell machinery by the virus imposes a translational "overload." Increased viral load can significantly trigger ER stress pathways, specifically unfolded protein response (UPR), an essential translation regulator.
Macroautophagy, a significant cellular homeostatic process, is essential for cellular health because it recycles misfolded proteins, damaged cell organelles, and exogenous particles in double-membrane multilayered vesicles (autophagosomes). Since autophagosomes originate in the ER membrane, UPR pathways are closely linked to the upregulation of autophagy, and several reports suggest cellular crosstalk among essential proteins from both pathways. Besides, autophagy also plays a critical role in RNA virus infection, and double-stranded (double-strand) RNA replication intermediates are often colocalized with autophagosomes in infected cells.
The present collection aims to understand UPR and autophagy in RNA virus infection, employing visualization experiments like viral quantification assays, fluorescence and electron microscopy, and western blotting. In addition, a better insight into the mechanisms of viral infection in regulating the stress and homeostatic pathways in the infected host cell will prove beneficial in antiviral therapy design.