Positive-Sense RNA Viruses and Coronaviruses

Positive-sense single-stranded RNA viruses carry a genome that can act directly as messenger RNA, so the incoming genome is immediately translated by host ribosomes to launch infection. This large and medically important group includes the picornaviruses (poliovirus, rhinovirus, hepatitis A), flaviviruses (dengue, Zika, yellow fever, hepatitis C), togaviruses, and the coronaviruses responsible for SARS, MERS, and COVID-19.

Definition

Positive-sense RNA viruses are RNA viruses whose single-stranded genome has the same polarity as messenger RNA and can be translated directly by host ribosomes upon entry; in humans they include the families Picornaviridae, Flaviviridae, Togaviridae, and Coronaviridae, among others.

Scope

The entry introduces positive-sense RNA virus families, their distinctive replication strategy, and the human diseases they cause, with particular attention to the coronaviruses as agents of recent epidemics and a pandemic. It is a reference overview of viral biology and epidemiology and does not provide clinical management or treatment guidance.

Core questions

• Why can the genome of a positive-sense RNA virus serve directly as messenger RNA?
• What features of coronaviruses underlie their capacity for cross-species transmission and emergence?
• How does the high mutation rate of RNA viruses affect disease and control?

Key concepts

• Positive-sense single-stranded RNA genome
• Direct translation of the genome
• RNA-dependent RNA polymerase
• High mutation and recombination rates
• Picornaviridae (poliovirus, rhinovirus, hepatitis A)
• Flaviviridae (dengue, Zika, hepatitis C)
• Coronaviridae (SARS-CoV, MERS-CoV, SARS-CoV-2)
• Zoonotic emergence

Key theories

Coronavirus zoonotic origin and evolution

Comparative and phylogenetic studies indicate that the major pathogenic human coronaviruses descend from animal reservoirs, chiefly bats, with spillover and adaptation producing SARS-CoV, MERS-CoV, and SARS-CoV-2.

Mechanisms

Because their genome has messenger-sense polarity, positive-strand RNA viruses can be translated immediately on entering the cell, producing the proteins needed to replicate the genome, including a virus-encoded RNA-dependent RNA polymerase that lacks proofreading in many families and so generates high mutation rates. Coronaviruses are exceptional among RNA viruses in carrying a proofreading exonuclease and a large genome, and they replicate via a nested set of subgenomic messenger RNAs. Their spike proteins mediate receptor binding and entry, and changes in this protein influence host range and transmissibility, contributing to zoonotic emergence.

Clinical relevance

Positive-sense RNA viruses cause a broad spectrum of human disease, from the common cold and poliomyelitis to dengue, viral hepatitis, and severe respiratory illness from coronaviruses. Their biology explains why some cause acute self-limited illness while others establish chronic infection or cause epidemics. This entry describes mechanisms and disease associations and is not a basis for individual diagnosis or treatment.

Epidemiology

This group includes globally distributed endemic viruses and major epidemic and pandemic agents; the coronaviruses produced the 2003 SARS outbreak, MERS, and the COVID-19 pandemic, while flaviviruses such as dengue cause large recurrent epidemics in tropical regions.

Evidence & guidelines

Genomic and clinical reports characterising SARS-CoV, MERS-CoV, and SARS-CoV-2, together with reference virology texts, document the biology and emergence of these viruses; the rapid genomic identification of SARS-CoV-2 in 2020 exemplifies how positive-sense RNA virus outbreaks are now investigated.

History

Poliovirus, a picornavirus, was central to the early molecular study of RNA viruses and to one of the great achievements of vaccination. The coronaviruses moved from relatively minor respiratory pathogens to the front of global health with the 2003 SARS epidemic, the later emergence of MERS, and the identification of SARS-CoV-2 in 2019-2020, which underscored the pandemic potential of zoonotic positive-sense RNA viruses.

Key figures

• Vincent Racaniello
• Zheng-Li Shi
• David Baltimore

Seminal works

• cui-2018
• zhu-2020
• ksiazek-2003

Frequently asked questions

What makes a virus 'positive-sense'?

Its RNA genome has the same polarity as messenger RNA, so once inside a cell it can be translated directly by host ribosomes without first being copied into a complementary strand.

Why have coronaviruses caused several recent epidemics?

Coronaviruses circulate in animal reservoirs such as bats and can adapt to new hosts; changes in their spike protein can allow spillover into humans, as seen with SARS-CoV, MERS-CoV, and SARS-CoV-2.