BiP: Master Regulator of the Unfolded Protein Response and Crucial Factor in Flavivirus Biology

Yale J Biol Med. 2017 Jun 23;90(2):291-300. eCollection 2017 Jun.

Abstract

Flaviviruses have an intimate relationship with their host cells, utilizing host proteins during replication. Much of viral genome replication and virion assembly occurs on and within the endoplasmic reticulum (ER). As a cellular protein folding hub, the ER provides an ideal environment for flaviviruses to replicate. Flaviviruses can interact with several ER processes, including the unfolded protein response (UPR), a cellular stress mechanism responsible for managing unfolded protein accumulation and ER stress. The UPR can alter the ER environment in several ways, including increasing ER volume and quantity of available chaperones, both of which can favor viral replication. BiP, a chaperone and master regulator of the UPR, has been demonstrated to play a key role in several flavivirus infections. Here we describe what is known in regard to BiP, its implicated role with flavivirus infection, and what remains to be discovered.

Keywords: BiP; GRP78; Japanese encephalitis; Kunjin; West Nile; dengue; tick-borne encephalitis virus; unfolded protein response.

Publication types

  • Review

MeSH terms

  • Animals
  • Endoplasmic Reticulum Chaperone BiP
  • Flavivirus / physiology*
  • Flavivirus Infections / metabolism
  • Flavivirus Infections / virology
  • Heat-Shock Proteins / physiology*
  • Humans
  • Unfolded Protein Response / physiology*
  • Virus Replication / physiology

Substances

  • Endoplasmic Reticulum Chaperone BiP
  • HSPA5 protein, human
  • Heat-Shock Proteins