Human parainfluenza viruses

Did You Know?

• Diagnosis can be made via cell culture, immunofluorescence, enzyme immunoassays, PCR, or analysis of IgG antibody titers in paired serum specimens.
• Maternal antibodies from colostrum in breast milk may offer some protection against HPIVs in early life.

Classification

The first HPIV was discovered in the late 1950s. Taxonomic division is based on antigenic and genetic characteristics, forming four major serotypes considered distinct viruses. HPIV-1 and HPIV-3 belong to the genus Respirovirus, while HPIV-2 and HPIV-4 belong to Rubulavirus. The viruses are enveloped and contain single-stranded negative-sense RNA; non-infectious virions with positive-polarity RNA have also been reported. The genome is about 15,000 nucleotides and encodes six structural proteins in the order 3′-NP-P-M-F-HN-L-5′. Reverse genetics has revealed that the most efficient replication and transcription occur when the genome nucleotide total is divisible by six, a pattern termed the 'rule of six,' though exceptions exist. The molecular weights of the proteins are similar across serotypes except for the phosphoprotein, which varies significantly. Viral replication begins with attachment and fusion via the hemagglutinin–neuraminidase (HN) and fusion (F) proteins; the F protein is cleaved from inactive F0 into active F1 and F2. The nucleocapsid then enters the cytoplasm, and transcription is carried out by the viral RNA-dependent RNA polymerase (L protein), with host ribosomes translating viral mRNA.

Clinical significance

HPIV-1, HPIV-2, and HPIV-3 are linked with up to a third of the estimated 5 million lower respiratory infections (LRI) in US children each year. Upper respiratory infections also occur but to a lesser extent. About 75% of children aged 5 or older have antibodies to HPIV-1. Symptoms include fever, cough (mild, barky, or with mucus), runny or stuffy nose, sore throat, wheezing, hoarseness, and sneezing. Approximately 25% of infants and young children develop clinically significant disease. Repeated infection throughout life is common, with later episodes causing upper respiratory illness such as colds and sore throat. The incubation period for all serotypes is 1 to 7 days. In immunosuppressed individuals, HPIV infections can cause severe, sometimes fatal pneumonia. HPIV-1 and HPIV-2 are the principal causes of croup (laryngotracheobronchitis), mainly in children aged 6–48 months, with biennial autumn epidemics; HPIV-1 outbreaks in the US occur during odd-numbered years. HPIV-3 is closely associated with bronchiolitis and pneumonia, primarily in infants under one year. HPIV-4 is infrequently detected but likely more common, often causing mild or asymptomatic infections; by age 10, most children are seropositive. HPIVs are associated with febrile seizures, with HPIV-4b showing the strongest association (62% of hospitalizations), followed by HPIV-3 (17%) and HPIV-1 (7%). Rare cases of viral meningitis and Guillain–Barré syndrome have also been linked to HPIVs.

Morbidity and mortality

Mortality from HPIVs in developed regions is rare, occurring mainly in the very young, elderly, and immunocompromised. Long-term airway remodeling is a significant cause of morbidity, and associations with chronic obstructive pulmonary disease (COPD) are under investigation. In developing regions, preschool children face the highest mortality risk, which may result from primary viral infection or secondary bacterial infection; predispositions such as malnutrition and vitamin A deficiency increase mortality. Lower respiratory infections cause about 25–30% of all deaths in preschool children in the developing world, and HPIVs are associated with 10% of all LRI cases. Other risk factors include absence of breastfeeding, environmental pollution, and overcrowding.

Differences between influenza and parainfluenza

Influenza viruses belong to the Orthomyxoviridae family, while parainfluenza viruses (HPIVs) belong to the Paramyxoviridae family. Influenza typically causes more severe illness, with high fever, body aches, and fatigue, whereas parainfluenza often produces milder, cold-like symptoms. Influenza has a distinct winter seasonal pattern, while HPIVs circulate year-round with type-specific patterns. Influenza is more likely to cause severe pneumonia in high-risk groups; parainfluenza is more likely to cause croup in children. Effective vaccines and antiviral medications exist for influenza, but none are available for parainfluenza. Parainfluenza primarily infects young children, with most infected by age 5, while influenza affects all ages.