Orthomyxoviruses and Paramyxoviruses

This group includes RNA viruses that primarily infect the respiratory tract, along with the measles and mumps viruses. Orthomyxoviruses have segmented genomes, while Paramyxoviruses have non-segmented genomes. Paramyxoviruses include measles, mumps, parainfluenza, and respiratory syncytial virus (RSV).

Influenza viruses

Influenza viruses belong to the Orthomyxovirus family. Their genomic RNA has 8 segments. They have triangular haemagglutinin (H) spikes and mushroom-shaped neuraminidase (N) spikes on their surface.

• Haemagglutinin (H):

  • Responsible for attachment to host tissue.
  • Antibodies formed against haemagglutinin are protective.
  • Has 15 subtypes (H1 to H15).

• Neuraminidase (N):

  • Important for release of progeny virus particles from the surface of an infected cell.
  • Helps break down the protective mucus coat in the respiratory tract.
  • Antibodies to neuraminidase are not protective.
  • Has 9 subtypes (N1 to N9).

• Non-structural protein NS1:

  • Important in virulence.
  • Inhibits host immune responses by interfering with interferon synthesis and function.

Depending on the types of ribonucleoprotein antigen, influenza viruses can be classified into three types: A, B, and C.

• Most pandemics are caused by Influenza A.
• Major outbreaks are caused by Influenza B.
• Non-epidemic, minor infections are caused by Influenza C.

Antigenic drift: Process of minor change in the genome due to mutation in the genes coding for H and N antigens. This happens continually over time as the virus replicates. Responsible for epidemics.

Antigenic shift: An abrupt, major change in the genes coding for H and N antigens caused by genetic reassortment of RNA segments (also called genetic recombination). Typically emerges in animals and then spreads to humans. Most of us will not have immunity to such novel viruses. Responsible for pandemics.

Clinical features: Influenza is transmitted by respiratory droplets and by contact with objects contaminated with the virus (e.g., a contaminated door knob to hands and then to the nose). It starts abruptly with fever, malaise, myalgias, sore throat, headache, and cough. Rarely, vomiting and diarrhea can occur. It may cause interstitial pneumonia. More commonly, it may cause secondary bacterial pneumonia. It may be complicated by myocarditis, encephalitis, or Reye’s syndrome.

Laboratory diagnosis of influenza: Nasal and throat swabs, respiratory secretions or washings, and sputum can be collected as samples.

• Viral antigen can be demonstrated by immunofluorescence.
• Nucleic acid can be detected by RT PCR (reverse transcriptase PCR). Can you guess why RT PCR and not regular PCR is used? Let us know!
• Cell culture can be done on embryonated eggs or monkey kidney culture.
• CFT and haemagglutination tests can be used for the detection of antibodies.

Early diagnosis is essential for effective treatment. Rapid influenza tests are available.

• Rapid tests are immunoassays that can identify the presence of influenza A and B viral nucleoprotein antigens or neuraminidase in respiratory specimens.
• They can give results in 15 minutes.
• Drawback is that they are less sensitive compared to PCR and culture, especially for type B.

Measles virus

Measles virus is included in the genus Morbillivirus. Its envelope has two lipoprotein spikes: haemagglutinin and fusion protein.

• Haemagglutinin: responsible for attachment to the host cell.
• Fusion protein: causes fusion of the viral envelope with the host cell membrane.

Measles is also called rubeola. It is highly contagious, with a greater than 90% secondary attack rate. There is immunosuppression during the infection, which may persist for a few months. It inhibits the production of IL 12.

Signalling lymphocyte activation molecule family member 1 (SLAMF1, also known as CD150), which is expressed by reticuloendothelial cells, and Nectin 4 expressed on epithelial cells have been identified as cellular receptors for measles virus.

Measles rash can potentially be explained by infection of the dermal endothelial cells and keratinocytes, which are subsequently cleared by the virus-specific host cellular immune response.

In malnourished children, vitamin A supplementation is protective against acquiring measles.

Clinical features: Infection starts with a prodrome of fever, malaise, conjunctivitis, and coryza, followed by Koplik’s spots. Koplik’s spots look like tiny white spots surrounded by a red ring and are seen on the inside of the cheek. This is followed by a maculopapular rash that starts on the face and then spreads down the body to include the palms and soles.

Complications include otitis media, bronchopneumonia, giant cell pneumonia, encephalitis, prolonged diarrhea, thrombocytopenia with bleeding, and secondary bacterial infections.

SSPE (subacute sclerosing panencephalitis) is a rare, late complication of measles occurring several years later. It presents as memory loss, irritability, myoclonic jerks, seizures, blindness, and finally coma.

Laboratory diagnosis of measles: Diagnosis is confirmed by detection of measles-specific IgM by ELISA or RT PCR.

• Respiratory and urine samples can be used for antigen detection.
• Giemsa-stained smears of respiratory secretions show characteristic multinucleated giant cells called Warthin-Finkeldey cells. These are infected cells that have fused due to the fusion protein.
• Viral antigens can also be detected by direct immunofluorescence.
• Tissue culture shows multinucleate syncytium formation with acidophilic nuclear and cytoplasmic inclusions.
• Presence of antibodies in CSF with classic history is useful to diagnose SSPE.

Mumps virus

Like measles virus, mumps virus has H and F antigens on the envelope. Two antigens are complement-fixing:

• V (viral) antigen
• S (soluble internal nucleocapsid) antigen

The virus has a predilection for the parotid glands, testes, ovaries, and pancreas.

Clinical features: Mumps is typically seen in children in the winter months. It presents with swollen unilateral or bilateral parotid glands, fever, malaise, etc. Complications include orchitis (which may cause infertility if both testes are involved), oophoritis, meningitis, pancreatitis, and nephritis.

Laboratory diagnosis of mumps:

• A fourfold rise in antibody titres on CFT or haemagglutination inhibition tests is diagnostic.
• Antibody to S antigen indicates current infection, while antibody to V antigen indicates current or past infection.
• IgM ELISA can be used for rapid diagnosis.
• Virus can be isolated from saliva, CSF, or urine in cell culture, which shows syncytium formation with acidophilic intracytoplasmic inclusions.
• Direct immunofluorescence can be used to detect viral antigens.

Respiratory syncytial virus or RSV

Instead of H and N spikes, RSV has G spikes for attachment to cell surface receptors and a fusion protein that causes syncytium formation. Infection is spread by respiratory droplets. It occurs in outbreaks in winter, causing severe infection in infants, while adults usually have a mild illness.

Clinical features:

• In infants, RSV causes bronchiolitis, pneumonia, and tracheobronchitis.
• In older children, it causes URTIs and otitis media.
• It may cause severe pneumonia in the elderly.
• It was previously associated with asthma, but recent research has proved that is not the case.

Laboratory diagnosis of RSV infections:

• An enzyme immunoassay or direct immunofluorescence can detect RSV antigens in samples like respiratory secretions or swabs.
• A fourfold rise of antibody titre detected by ELISA, CFT, neutralization test, or indirect immunofluorescence can be useful for diagnosis.
• In cell culture, it shows development of multinucleated giant cells.

Parainfluenza virus

Parainfluenza virus has H, N, and fusion protein spikes. Antibodies to H and fusion protein are protective. It is transmitted by respiratory droplets. It has 4 types.

• Types 1 and 2 cause croup (acute laryngotracheobronchitis) and pharyngitis.
• Croup presents as fever, barking cough, hoarse voice, sometimes labored breathing, and in severe cases, stridor and drooling, typically in a young child.
• Type 3 causes bronchitis, bronchiolitis, and pneumonia.
• Type 4 causes minor disease.

It also causes common cold and otitis media. Diagnosis is mainly clinical. In the laboratory, cell culture, ELISA, CFT, or neutralization tests can be done.