Viruses are microscopic biological entities that rely on a host organism’s cellular machinery to reproduce. While host cells and some viruses use deoxyribonucleic acid (DNA) as their genetic blueprint, a separate class of viruses uses ribonucleic acid (RNA) instead. This difference defines RNA viruses, a family of pathogens responsible for a significant proportion of infectious diseases. The unique structure and replication strategy of these viruses, particularly their relationship to messenger RNA (mRNA), explains their profound impact on human health.
Defining the mRNA Virus
An mRNA virus is a pathogen whose genetic information is stored in an RNA molecule rather than a DNA molecule. The viral particle, or virion, consists of the RNA genome encased in a protective shell of protein subunits called a capsid. Many of these viruses, such as influenza and coronaviruses, also possess an outer layer called an envelope. This envelope is a lipid membrane derived from the host cell and studded with viral glycoproteins that facilitate entry into new cells.
The fundamental difference between RNA and DNA is similar to the difference between a working copy and a master blueprint. In human cells, DNA is the stable master copy stored in the nucleus, and mRNA is the temporary working copy that carries instructions to the cell’s ribosomes. The RNA genome of an mRNA virus bypasses this system, bringing its own instructions directly into the cell’s cytoplasm. This allows the virus to avoid entering the host cell’s nucleus in most cases, resulting in a faster process of commandeering the cell.
Classification by Genome Polarity
The way an RNA virus’s genome functions as mRNA upon entry into the host cell is the basis for its primary classification, known as polarity or “sense.” Single-stranded RNA viruses are categorized as either positive-sense (+) or negative-sense (-) RNA viruses.
Positive-sense (+) RNA viruses have a genome with the same sequence as the host cell’s mRNA. This means the genome can be immediately recognized and translated by the host’s ribosomes, allowing for rapid production of viral proteins, including the specialized enzymes needed for replication. Examples of this group include coronaviruses and poliovirus.
Negative-sense (-) RNA viruses carry a genome that is complementary to the required mRNA, meaning it cannot be directly translated by the host machinery. It must first be transcribed into a positive-sense strand before protein synthesis can begin. To accomplish this, negative-sense viruses must carry their own specialized enzyme, RNA-dependent RNA polymerase (RdRp), packaged within the viral particle. This RdRp is immediately used upon infection to create the translatable positive-sense mRNA strand. Influenza, measles, and rabies viruses fall into this category.
Replication and Mutation Rates
The core process of an mRNA virus’s life cycle involves commandeering the host cell to mass-produce new viral particles, driven entirely by the viral genome’s instructions. After the virus enters the cell and uncoats, releasing its RNA genome, the viral RNA immediately begins translation (in the case of positive-sense) or transcription (in the case of negative-sense) to produce the necessary proteins. Among the first proteins created is the RNA-dependent RNA polymerase (RdRp). This RdRp enzyme is the central player in replication, synthesizing new copies of the viral genome from an RNA template.
The RdRp in most RNA viruses is notoriously error-prone, a trait directly linked to the virus’s high mutation rate. Unlike DNA polymerases in human cells, which possess proofreading mechanisms, the viral RdRp typically lacks this ability. Each time the RdRp copies the RNA genome, it introduces mutations at a rate that can range from \(10^{-6}\) to \(10^{-4}\) substitutions per nucleotide per replication. This high error rate creates a swarm of slightly different viral variants within the host, a phenomenon known as a quasispecies. The resulting genetic diversity allows the viral population to rapidly adapt to changes in the environment, such as escaping the host’s immune system or developing resistance to antiviral drugs.
Major Disease-Causing mRNA Viruses
The ability of mRNA viruses to rapidly replicate and mutate has made them responsible for some of the most impactful human diseases. These pathogens span a wide range of clinical presentations, from mild respiratory illness to severe hemorrhagic fever.
The coronavirus family, which includes the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) that causes COVID-19, are positive-sense RNA viruses that infect the respiratory tract. Another positive-sense example is the Zika virus, which is transmitted by mosquitoes and is known to cause birth defects.
Negative-sense RNA viruses include the influenza virus, which causes seasonal and pandemic respiratory illness and requires annual vaccine updates. The Rabies virus, a member of the Rhabdovirus family, is a bullet-shaped negative-sense virus that causes fatal neurological disease. Other highly pathogenic examples include the Ebola and Marburg viruses, which belong to the Filovirus family and cause severe hemorrhagic fevers with high mortality rates.