Modification of intracellular membrane structures for virus replication

Key Points

• Plus-stranded RNA viruses induce large membrane structures that might support the replication of their genomes. Similarly, cytoplasmic replication of poxviruses (large DNA viruses) occurs in associated membranes. These membranes originate from the endoplasmic reticulum (ER) or endosomes.

• Membrane vesicles that support viral replication are induced by a number of RNA viruses. Similarly, the poxvirus replication site is surrounded by a double-membraned cisterna that is derived from the ER.

• Analogies to autophagy have been proposed since the finding that autophagy cellular processes involve the formation of double-membrane vesicles. However, molecular evidence to support this hypothesis is lacking.

• Membrane association of the viral replication complex is mediated by the presence of one or more viral proteins that contain sequences which associate with, or integrate into, membranes.

• Replication-competent membranes might contain viral or cellular proteins that contain amphipathic helices, which could mediate the membrane bending that is required to form spherical vesicles.

• Whereas poxvirus DNA replication occurs inside the ER-enclosed site, for most RNA viruses the topology of replication is not clear. Preliminary results for some RNA viruses suggest that their replication could also occur inside double-membrane vesicles.

• We speculate that cytoplasmic replication might occur inside sites that are 'enwrapped' by an ER-derived cisterna, and that these cisternae are open to the cytoplasm. Thus, RNA and DNA viruses could use a common mechanism for replication that involves membrane wrapping by cellular cisternal membranes.

• We propose that three-dimensional analyses using high-resolution electron-microscopy techniques could be useful for addressing this issue. High-throughput small-interfering-RNA screens should also shed light on molecular requirements for virus-induced membrane modifications.

Abstract

Many viruses induce the formation of altered membrane structures upon replication in host cells. This Review examines how viruses modify intracellular membranes, highlights similarities between the structures that are induced by viruses from different families and discusses how these structures could be formed.

Abstract

Viruses are intracellular parasites that use the host cell they infect to produce new infectious progeny. Distinct steps of the virus life cycle occur in association with the cytoskeleton or cytoplasmic membranes, which are often modified during infection. Plus-stranded RNA viruses induce membrane proliferations that support the replication of their genomes. Similarly, cytoplasmic replication of some DNA viruses occurs in association with modified cellular membranes. We describe how viruses modify intracellular membranes, highlight similarities between the structures that are induced by viruses of different families and discuss how these structures could be formed.