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Paramyxoviruses are negative-sense single-stranded RNA viruses that cause a wide variety of diseases in humans and animals. The majority of paramyxoviruses are respiratory pathogens, and transmission occurs via aerosols or direct contact with infectious secretions, or in some cases by fecal-oral contact.
Paramyxoviridae contain two subfamilies: Paramyxovirinae and Pneumovirinae. The Paramyxovirinae subfamily contains five genera: Respirovirus (human parainfluenza virus 3, Sendai), Rubulavirus (mumps, human parainfluenza virus 5), Avulavirus (avian parainfluenza, Newcastle disease), Morbillivirus (measles, canine distemper), and Henipavirus. The second subfamily, Pneumovirinae, contains Pneumovirus and Metapneumovirus, as well as animal pathogens such as human and bovine respiratory syncytial viruses and human and avian metapneumovirus.
Parainfluenza viruses (HPIV) are divided into four groups (types 1-4) and are all enveloped, negative-sense RNA genomes that cause lower respiratory infections in children, the immunocompromised, and the elderly. These viruses also cause significant veterinary disease. There are two genera of HPIV: the Respirovirus (HPIV-1 and HPIV-3) and Rubulavirus (HPIV-2 and HPIV-4). Both differ from influenza viruses by their non-segmented genomes, and from other genera of Paramyxoviridae by the absence of a neuraminidase or nucleocapsid morphology. These viruses are between 150 and 250 nm and contain a 15,000-nucleotide (-)ssRNA genome that encodes structural proteins (N, P, C, M, F, HN, L). Two surface glycoproteins are found in all HPIV: the hemagglutinin-neuraminidase (HN) and the fusion protein (F0). Beneath the viral membrane is the M (membrane) protein. The P gene produces several nonstructural proteins from overlapping reading frames that aid in viral replication or slow the cell cycle; the V and C proteins may also inhibit the interferon response by inducing degradation of STAT1 or STAT2. The nucleocapsid comprises viral RNA together with the N, P, and L proteins. The surface glycoproteins HN and F interact with the M protein to direct insertion and aggregation at the cell membrane, with the M protein participating in cell budding.
The virus first enters the cell by fusing the viral and host cell lipid membranes, followed by release of the HPIV nucleocapsid into the cytoplasm. Replication then takes place using the viral RNA-dependent RNA polymerase (L protein). The cellular ribosomal machinery translates viral mRNA into proteins, which then direct the full-length replication of the viral genome, first into (+)-sense RNA, then into the (-)-sense RNA strand. These (-)ssRNA strands are then encapsidated with NP and packaged for export as a new virion.
HPIV can infect many different animals, including birds, primates, and rodents. Some parainfluenza viruses can infect poultry and penguins (Newcastle disease virus).
Clinical features of HPIV infection include both upper and lower respiratory tract illnesses. Children present with fever, croup, laryngeal obstruction, and inspiratory stridor. The virus can also cause bronchiolitis in infants, pneumonia in children, tracheobronchitis, and giant-cell pneumonia in immunocompromised individuals. It has been associated with neurologic disease including seizures, encephalitis, and demyelinating syndromes, suggesting the virus can be neurotropic.
Another important disease-causing member of the Rubulavirus genus is the mumps virus (MuV), which causes parotitis and orchitis and is also highly neurotropic and may cause encephalitis and meningitis. Although the disease is self-limiting and rarely fatal, long-term sequelae can occur, including seizures, deafness, and paralysis. The virus is transmitted by inhalation or oral contact with droplets, and the hallmark is salivary gland swelling, with viral replication occurring bilaterally in the parotid glands. Unilateral orchitis is the most common extra-salivary organ infection by mumps virus; atrophy of the testicle can occur in half of cases, but sterility is a rare complication. The virus can also infect the kidneys and cause nephritis, as well as pancreatitis in a small percentage of cases. Half of infection cases show virus within the cerebrospinal fluid and infect neurons in the brain, but meningitis and encephalitis are rare complications. Deafness can also occur as a consequence of infection within the inner ear.
Henipavirus and Nipah virus have broad tropism and extreme virulence and infect bats, which can transmit to humans either directly or via an intermediate host. Due to their high virulence, they are classified as BSL-4 pathogens.