Coronaviruses post-SARS: update on replication and pathogenesis

Abstract

Coronaviruses are positive strand RNA viruses that cause disease in humans, and domestic and companion animals. They are most notorious for causing severe acute respiratory syndrome (SARS) outbreaks in 2002–2003. All coronaviruses follow the same basic strategy of replication. All coronaviruses encode 15 or 16 replicase related proteins, 4 or 5 structural proteins and 1–8 group-specific or accessory proteins. Many of the replicase proteins are assembled into replication machinery in double-membrane vesicles (DMVs) and on a reticular network of membranes that are derived from the endoplasmic reticulum. Coronaviruses are readily transmitted across species. This phenomenon was illustrated when the SARS-coronavirus crossed species from bats to intermediate hosts, such as palm civets, and then to humans. It also explains the large number of species, including humans, that are infected with viruses closely related to bovine coronavirus. In many coronavirus infections, disease severity increases during virus clearance, suggesting that the host immune response is both protective and pathogenic. Furthermore, inhibition of specific aspects of the immune response results in less severe disease and less tissue destruction, without diminishing the kinetics of virus clearance. Like all successful viruses, coronaviruses have evolved both passive and active mechanisms to evade the interferon response. Replication in DMVs may contribute to passive evasion of the innate immune response by making double-stranded RNA inaccessible to cellular sensors.