Myxoviruses are a group of enveloped RNA viruses responsible for widespread respiratory and systemic diseases in humans. These viruses are characterized by a flexible, often spherical shape and a genetic structure composed of ribonucleic acid (RNA) enclosed within a protein shell. The myxovirus group is classified into two major families, Orthomyxoviridae and Paramyxoviridae, both of which possess a fatty outer membrane, or envelope, derived from the host cell. These pathogens cause recurring seasonal outbreaks and have the potential to trigger global pandemics.
Classification and Defining Characteristics
Myxoviruses are defined by their affinity for mucins, which are glycoproteins found on cell surfaces, particularly in the respiratory tract. Both the Orthomyxoviridae and Paramyxoviridae families contain a single-stranded, negative-sense RNA genome and a helical nucleocapsid structure. The viral envelope is studded with glycoprotein spikes that mediate attachment and entry into host cells.
The two families are distinguished primarily by the organization of their RNA genome. Orthomyxoviruses, which include the influenza viruses, possess a segmented genome, typically consisting of eight separate RNA pieces. This segmentation enables genetic reassortment. These viruses are relatively small, measuring between 80 and 120 nanometers in diameter.
In contrast, Paramyxoviruses have a non-segmented, linear RNA genome, with all genetic information contained on a single molecule. Paramyxoviruses are generally larger, with diameters ranging from 150 to 300 nanometers. Orthomyxoviruses also differ in their replication strategy, requiring the host cell nucleus for part of their life cycle, while Paramyxoviruses complete replication solely within the host cell cytoplasm.
The surface glycoproteins also show structural differences. Orthomyxoviruses typically display two distinct surface spikes: hemagglutinin (HA) for binding and neuraminidase (NA) for release. Paramyxoviruses, such as mumps and parainfluenza viruses, often have both HA and NA activity combined on a single protein spike, though some, like Respiratory Syncytial Virus (RSV), lack both activities entirely.
Major Diseases Caused by Myxoviruses
Orthomyxoviruses (Influenza)
The Orthomyxovirus family causes influenza, an acute febrile illness affecting the upper and lower respiratory tracts. Influenza is categorized into Types A, B, and C. Type A viruses are the most significant due to their ability to infect multiple species and cause major epidemics and pandemics. Type A influenza undergoes rapid genetic change through antigenic shift and drift, allowing it to evade host immunity and necessitating annual vaccine updates.
Influenza B viruses primarily circulate in humans and cause less severe, localized outbreaks, while Type C generally results in mild respiratory illness. Infection from any type can lead to complications such as pneumonia, particularly in high-risk populations. Symptoms like fever, muscle aches, and malaise are characteristic of influenza infection.
Paramyxoviruses
The Paramyxovirus family is responsible for a broader range of diseases, many of which are common childhood infections.
Measles, caused by the Morbillivirus genus, begins with fever, cough, runny nose, and conjunctivitis. The appearance of Koplik spots—tiny white spots on a red background found inside the mouth—precedes the characteristic maculopapular rash that spreads across the body.
Mumps virus causes painful swelling of the parotid salivary glands. It can also lead to serious complications, including inflammation of the testes (orchitis) in post-pubertal males, which carries a risk of infertility, or inflammation of the membranes surrounding the brain (meningitis).
Respiratory Syncytial Virus (RSV) is the most common cause of lower respiratory tract infections in infants and young children. RSV infection can lead to severe conditions like bronchiolitis (inflammation of the small airways) and pneumonia. Parainfluenza viruses (HPIV 1-4) often cause croup in children, characterized by a distinctive barking cough.
Viral Replication Cycle
The infection cycle begins when the virus attaches to a host cell, mediated by a surface glycoprotein. For influenza, the hemagglutinin protein binds specifically to sialic acid receptors on the respiratory epithelial cell surface. This binding triggers the host cell to engulf the virus through endocytosis, placing the virion inside a cellular vesicle.
Inside the endosome, a change in acidity activates the viral fusion process. For Orthomyxoviruses, the M2 ion channel protein allows hydrogen ions to enter the viral core, facilitating the uncoating of the virus and the release of the viral ribonucleoprotein (vRNP) complexes into the cytoplasm. These vRNPs are then transported into the host cell nucleus, a unique step for influenza among RNA viruses.
Inside the nucleus, the viral RNA-dependent RNA polymerase (RdRp) uses the negative-sense genomic RNA as a template to synthesize new viral messenger RNA (mRNA) and replicate the genome. This polymerase is also responsible for “cap-snatching,” where it steals the 5′ caps from host cell mRNAs to prime its own transcription. The newly manufactured viral components are then transported to the cell membrane for assembly.
The final stage is the release of new viral particles, which bud from the host cell membrane, acquiring their lipid envelope and surface proteins. The newly formed virions can re-bind to sialic acid receptors on the same cell via their hemagglutinin. The neuraminidase enzyme cleaves the sialic acid receptors from the host cell and the viral surface, preventing aggregation and allowing them to spread to new cells.
Prevention and Control Measures
Control of myxovirus infections relies primarily on vaccination, which stimulates the immune system to recognize and neutralize the virus. Influenza vaccines are typically multivalent, containing components of the most likely circulating influenza A and B strains predicted for the upcoming season. These vaccines are primarily administered as inactivated (killed) vaccines, but live attenuated vaccines are also used in specific populations.
For Paramyxoviruses, highly effective live attenuated vaccines are available, most notably the Measles, Mumps, and Rubella (MMR) vaccine, which provides long-lasting immunity.
Antiviral drugs offer a second layer of defense, especially for treating influenza. A major class of antivirals are the neuraminidase inhibitors (e.g., oseltamivir and zanamivir), which target the viral release step. By blocking the neuraminidase enzyme, these drugs trap the newly formed virions on the surface of the infected cell, preventing them from spreading further. M2 ion channel blockers were previously used for influenza A, but their use is now limited due to widespread viral resistance.