Opportunistic intruders: how viruses orchestrate ER functions to infect cells

Abstract

Viruses subvert the functions of their host cells to replicate and form new viral progeny. The endoplasmic reticulum (ER) has been identified as a central organelle that governs the intracellular interplay between viruses and hosts. In this Review, we analyse how viruses from vastly different families converge on this unique intracellular organelle during infection, co-opting some of the endogenous functions of the ER to promote distinct steps of the viral life cycle from entry and replication to assembly and egress. The ER can act as the common denominator during infection for diverse virus families, thereby providing a shared principle that underlies the apparent complexity of relationships between viruses and host cells. As a plethora of information illuminating the molecular and cellular basis of virus–ER interactions has become available, these insights may lead to the development of crucial therapeutic agents.

EMC1-dependent stabilization drives membrane penetration of a partially destabilized non-enveloped virus

“…For example, a series of recent reports suggest that the EMC plays a critical role during flavivirus (including Zika, Dengue, and West Nile virus) infection (Ma et al, 2015; Savidis et al, 2016; Marceau et al, 2016; Zhang et al, 2016). As a wealth of literature has established that replication and assembly of flaviviruses are events in their life cycle associated with the ER membrane (Ravindran et al, 2016), it is perhaps not surprising that this ER membrane protein complex might exert a role during their infection. However, despite these reports, the molecular basis by which the EMC controls flavivirus infection remains completely unknown.…”

Organelle dynamics and viral infections: at cross roads

“…Several viral proteins need to be glycosylated at their N-terminal to ensure proper folding and for the incorporation into virions [71]. Hence, a common phenomenon observed upon viral infection is interference with the host post translational machinery and competition with the cellular proteins to undergo these modifications [72].…”

“…Later, SV40 particles travel across the ER membrane to reach the cytosol [76]. Many enveloped and non-enveloped viruses that exploit ER functions like UPR, ERAD to facilitate their replication have been discussed elsewhere [71].…”

A scorpion venom peptide Ev37 restricts viral late entry by alkalizing acidic organelles

“…There are many viruses threatening human health throughout the world. They include Flaviviridae (dengue virus, HCV, 3 Zika virus, West Nile virus, and Japanese encephalitis virus), Coronaviridae (severe acute respiratory syndrome), Retroviridae (HIV-1), and other viruses (1). Many people die every year due to viral infection.…”

“…Many people die every year due to viral infection. Dengue virus, including four serotypes (DENV [1][2][3][4], is an emerging threat to billions of people worldwide (2). Some disappointing therapeutic trials in dengue infection investigating both antivirals and adjunctive therapies have been carried out in recent years, such as balapiravir in Vietnam, and dengvaxia, the first clinically approved dengue vaccine, recently was recommended for use in areas where the disease is highly prevalent because of its side effects (3,4).…”