The dependence of viral RNA replication on co-opted host factors

Key Points

• Positive-strand RNA ((+)RNA) viruses are major pathogens of humans, animals and plants. These viruses actively reprogramme the host cell metabolism to support the infection process and to allow viruses to escape or suppress host defence mechanisms.

• To facilitate RNA replication, (+)RNA viruses interact with numerous host molecules via protein–protein, RNA–protein and protein–lipid interactions. These interactions are crucial for the formation of viral replication organelles, which produce new viral RNA progeny in host cells.

• All characterized (+)RNA viruses assemble viral replication complexes, containing both viral and host proteins, on intracellular membranes. The subverted host factors play crucial parts in all steps of (+)RNA virus replication. Therefore, host factors are key determinants of viral pathology as well as viral evolution.

• As there can be ∼20,000–30,000 different proteins in a typical eukaryotic cell, identifying all the proteins that are subverted by a given (+)RNA virus is a daunting task. Genome-wide and global proteomics approaches have recently emerged as a powerful means to identify the host factors involved in (+)RNA virus replication.

• An emerging theme from the genome-wide screens is that many of the host proteins subverted for (+)RNA virus replication are unique for a given virus. This suggests that (+)RNA viruses have evolved different ways to utilize host cell resources.

• In spite of the diverse sets of host factors co-opted by various viruses, functional and mechanistic studies suggest that different host proteins provide similar functions during viral RNA replication.

• Common host factors that are recruited by (+)RNA viruses for their replication include: RNA-binding proteins that facilitate viral RNA synthesis; proteins involved in membrane bending that contribute to the formation of membrane-bound replication complexes; lipid synthesis enzymes that affect lipid composition and have a role in making a favourable microenvironment for viral replication; and chaperones and prolyl isomerases that facilitate the proper folding and functions of viral replication proteins during assembly of the viral replication complexes.

Abstract

The replication of positive-sense RNA ((+)RNA) viruses involves numerous interactions between the RNA and proteins of the virus and proteins, membranes and lipids of the host. Host factors are thus key determinants of viral pathology as well as viral evolution. In this Review, Nagy and Pogany outline our current understanding of the host factors that facilitate the replication of (+)RNA viruses.

Abstract

Positive-sense RNA ((+)RNA) viruses such as hepatitis C virus exploit host cells by subverting host proteins, remodelling subcellular membranes, co-opting and modulating protein and ribonucleoprotein complexes, and altering cellular metabolic pathways during infection. To facilitate RNA replication, (+)RNA viruses interact with numerous host molecules through protein–protein, RNA–protein and protein–lipid interactions. These interactions lead to the formation of viral replication complexes, which produce new viral RNA progeny in host cells. This Review presents the recent progress that has been made in understanding the role of co-opted host proteins and membranes during (+)RNA virus replication, and discusses common themes employed by different viruses.