Opportunistic intruders: how viruses orchestrate ER functions to infect cells

• Published in: Nature reviews. Microbiology 2016-07, Vol.14 (7), p.407-420
• Main Authors: Ravindran, Madhu Sudhan, Bagchi, Parikshit, Cunningham, Corey Nathaniel, Tsai, Billy
• Format: Article
• Language: English
• Subjects: 631/250/255/2514; 631/326/596/2557; 631/80/642/1463; Animals; Antiviral agents; Biosynthesis; Cytosol; Dengue fever; Dismantling; DNA biosynthesis; DNA Replication; DNA viruses; Egress; Endoplasmic reticulum; Endoplasmic Reticulum - physiology; Endoplasmic Reticulum - virology; Enzymes; Genome, Viral; Genomes; Health aspects; Hepatitis C; Homeostasis; Host-Pathogen Interactions; Humans; Immunoglobulins; Infection; Infections; Infectious Diseases; Inhibitors; Life cycles; Life Sciences; Lipids; Medical Microbiology; Membranes; Microbiology; Morphogenesis; Parasitology; Physiological aspects; Polypeptides; Prevention; Proteins; Replication; review-article; Ribonucleic acid; RNA; RNA viruses; Rotavirus; Structural proteins; Toxicity; Vector-borne diseases; Viral infections; Virology; Virus Assembly; Virus Diseases - therapy; Virus Diseases - virology; Virus Internalization; Virus Replication - genetics; Viruses; Viruses - genetics; Viruses - metabolism; West Nile virus
• ISSN: 1740-1526; 1740-1534
• DOI: 10.1038/nrmicro.2016.60

Key Points Viruses exploit the functions of the endoplasmic reticulum (ER) to promote both early and later stages of their life cycle, including entry, translation, replication, assembly, morphogenesis and egress. This observation reveals a shared principle that underlies virus–host cell relationships. Viral entry often requires disassembly of the incoming virus particle. This is best exemplified in the case of polyomavirus entry, in which ER-associated machineries are hijacked to disassemble the virus and promote entry to the cytosol en route to the nucleus. Many enveloped viruses, such as HIV and influenza virus, co-opt the ER-associated protein biosynthetic machinery to translate their genome and produce structural proteins that are necessary for the formation of virus particles and non-structural proteins that are essential during genome replication. Replication of the viral genome, particularly for positive-sense RNA ((+)RNA) viruses including hepatitis C virus (HCV), dengue virus (DENV) and West Nile virus (WNV), occurs in virus-induced membranous structures that are most often derived from the ER. The formation of these structures requires morphological changes to the ER membrane, involving membrane rearrangements that are induced by viral non-structural proteins that are targeted to the ER. As virus assembly is often coupled to genome replication, the assembly process frequently relies on the ER membrane. This strategy is seen for both RNA and DNA viruses. Morphogenesis of assembled virus particles can also take advantage of the ER. This is best observed in the non-enveloped rotavirus, for which a transient enveloped intermediate is converted to the mature and infectious particle in the lumen of the ER. After maturation in the ER, progeny virus particles egress the host through the ER-dependent secretory pathway, which provides a physical conduit to the extracellular environment. The overall observations that the ER actively promotes all steps of viral infection have therapeutic implications. The development of chemical inhibitors of selective ER-associated components is emerging as a potential avenue of antiviral therapy, provided that these inhibitors have minimal toxicity to the host cell. Many host structures are vital for viral infection and the endoplasmic reticulum (ER), in particular, is essential. In this Review, Tsai and colleagues highlight examples of subversion of the ER by diverse viruses to promote all stages of their life cycle, fro