RNA virus

RNA viruses are infectious agents distinguished by genomes composed of ribonucleic acid (RNA). Unlike DNA viruses, these viruses store their genetic information in either single-stranded RNA (ssRNA) or double-stranded RNA (dsRNA) molecules. RNA viruses infect a wide range of hosts, including humans, animals, plants, fungi, and bacteria, and they are responsible for numerous significant human diseases. High mutation rates, diverse replication mechanisms, and complex evolutionary histories make RNA viruses a central focus of virology, epidemiology, and public health research.

General Characteristics and Diversity

The genomes of RNA viruses may be single-stranded or double-stranded and can vary widely in organisation, segmentation, and length. Single-stranded RNA viruses can be further classified by the polarity or “sense” of their RNA:

• Positive-sense ssRNA viruses: Their RNA resembles host mRNA and can be directly translated by host ribosomes.
• Negative-sense ssRNA viruses: Their RNA is complementary to mRNA and must first be transcribed into positive-sense RNA by a viral RNA-dependent RNA polymerase.
• Ambisense viruses: These viruses possess genomic regions of both positive and negative polarity, enabling translation from each strand under specific conditions.

Double-stranded RNA viruses exhibit extensive variation in capsid architecture, genome segmentation (ranging from one to twelve segments), and host range. Notable members of this group include rotaviruses, which are a major cause of gastroenteritis in children, and bluetongue virus, which affects livestock.
RNA viruses possess some of the highest mutation rates among biological systems because their RNA-dependent RNA polymerases lack the proofreading functions characteristic of most DNA polymerases. Retroviruses also exhibit high mutation rates as errors introduced during reverse transcription become fixed in the resulting viral DNA prior to integration into the host genome. Although many viral regions tolerate high variability, some genome segments remain highly conserved due to structural or functional constraints, such as the core-encoding region of the hepatitis C virus.

Taxonomy and Classification

The International Committee on Taxonomy of Viruses (ICTV) classifies all RNA viruses that replicate using homologous RNA-dependent RNA polymerases within the realm Riboviria. This realm includes viruses from Groups III, IV, and V of the Baltimore classification system, as well as retroviruses (Group VI), which utilise DNA intermediates during replication. Most RNA viruses fall within the kingdom Orthornavirae, while some taxa remain incertae sedis.
Certain RNA-based infectious agents, such as members of the families Avsunviroidae and Pospiviroidae, along with deltaviruses, were previously misclassified as RNA viruses but are not currently placed within Riboviria. Their inclusion was based on misunderstandings of evolutionary relationships inferred from the RNA-dependent RNA polymerase.
RNA virus classification is principally based on genome type, gene organisation, and replication strategy. ICTV recognises five orders and more than forty families of RNA viruses, although numerous genera and species remain unassigned. Comparative studies of thousands of viral genomes reveal several major monophyletic groups, including leviviruses, a picornavirus supergroup, an alphavirus–flavivirus lineage, the dsRNA viruses, and the negative-sense RNA viruses. Phylogenetic analyses suggest that lentiviruses form a basal clade, with subsequent divergence occurring between picornavirus-like and other major RNA virus lineages.
Within positive-sense RNA viruses, three major groups are identified based on RNA-dependent RNA polymerase phylogeny: the picorna-like group (Picornavirata), the flavi-like group (Flavivirata), and the alpha-like group. Modern ICTV taxonomy places these viruses into three phyla—Kitrinoviricota, Lenarviricota, and Pisuviricota—within Orthornavirae.

Major RNA Virus-Associated Diseases

RNA viruses are responsible for a wide array of human and animal diseases. Major human diseases caused by RNA viruses include influenza, SARS, MERS, COVID-19, dengue fever, hepatitis C and E, West Nile fever, Ebola virus disease, rabies, poliomyelitis, mumps, and measles. Retroviruses such as HIV-1 and HIV-2, although possessing an RNA genome, use DNA intermediates and are therefore placed in a separate Baltimore group; they cause AIDS and remain among the most medically significant RNA-related pathogens.

Genome Structure and Sequence Complexity

RNA viral genomes display considerable variability in sequence composition and redundancy. Double-stranded RNA viruses typically exhibit lower sequence redundancy compared to single-stranded RNA viruses, while dsDNA viruses possess the most redundant genomes and ssDNA viruses the least. Genome sequence complexity is an important characteristic used in modern, reference-free classification of viruses. Structural studies have demonstrated shared replication mechanisms and capsid architecture across diverse dsRNA families, reinforcing their evolutionary connectedness.

Replication Strategies

RNA viruses employ diverse replication mechanisms depending on their genome type:

• Double-stranded RNA viruses (Group III): Their segmented genomes directly serve as templates for transcription of positive-sense RNAs, each of which encodes one or more proteins.
• Positive-sense ssRNA viruses (Group IV): Their genomes function like mRNA and are translated immediately into viral proteins, including RNA-dependent RNA polymerase, which synthesises the complementary negative-sense strand to produce replicative intermediates.
• Negative-sense ssRNA viruses (Group V): These viruses must transport their own RNA-dependent RNA polymerase to transcribe their genomes into positive-sense RNA prior to translation.
• Retroviruses (Group VI): Although possessing RNA genomes, retroviruses replicate through a DNA intermediate using reverse transcriptase. The resulting double-stranded DNA integrates into the host genome and may subsequently produce new virions.

Recombination and Evolution

Genetic recombination is widespread among RNA viruses and is a major driver of viral evolution. Recombination can occur when multiple viral genomes infect the same host cell. In some viruses, such as HIV, strand switching during reverse transcription facilitates recombination, helping the virus avoid lethal genome damage. Recombination is also observed in positive-sense RNA viruses like poliovirus, in dsRNA viruses such as reovirus, and in negative-sense viruses such as influenza. RNA recombination contributes to genome rearrangements, adaptation, and occasionally the emergence of novel pathogenic strains.
Recombination between divergent lineages of animal viruses of the same species occurs infrequently but may result in recombinant viruses capable of causing outbreaks in human populations. Rarely, recombination between viral and host RNA can occur, although it is typically of limited biological significance.

Summary of Major Taxonomic Groups

Large-scale phylogenetic studies identify five broad evolutionary groupings within the RNA viruses:

• The levivirus and related bacteriophage group.
• The picornavirus supergroup.
• The alphavirus and flavivirus supergroup.
• The double-stranded RNA viruses.
• The negative-sense RNA viruses.

Positive-sense RNA viruses form the largest group and are organised into phyla within Orthornavirae. Their RNA-dependent polymerases further categorise them into picorna-like, flavi-like, and alpha-like groups, reflecting deep evolutionary relationships among RNA virus families.