Orthomyxoviruses and Paramyxoviruses

This group includes viruses that infect primarily the respiratory tract and Measles and Mumps viruses. They are RNA viruses, Orthomyxoviruses have segmented genomes while Paramyxoviruses have non segmented genomes. Paramyxoviruses include Measles, Mumps, Parainfluenza and Respiratory Syncytial Viruses.

Influenza Viruses

They belong to the Orthomyxovirus family. Their genomic RNA has 8 segments. They have triangular haemagglutinin and mushroom shaped neuraminidase spikes on their surface. Haemagglutinin is important for attachment to host tissue and antibodies formed against it are protective. It has 15 subtypes H1 to 15. Neuraminidase is important for the release of progeny virus particles from the surface of an infected cell and for breaking down protective mucus coat in the respiratory tract. Antibodies to neuraminidase are not protective. It has 9 subtypes N1 to 9. The Non Structural protein NS 1 is important in virulence. It causes inhibition of host immune responses by interfering with interferon synthesis and function.

Depending on the types of ribonucleoprotein antigen, Influenza virus can be classified into three types- A, B and C. Most pandemics are caused by Influenza A, major outbreaks are caused by Influenza B and non-epidemic, minor infections are caused by Influenza C.

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

Antigenic shift: It is 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: It is transmitted by respiratory droplets and by contact with objects contaminated with the virus e.g. contaminated door knob to hands and then to nose. It starts abruptly as 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, sputum can be collected as samples. Viral antigen can be demonstrated by immunofluorescence and 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

It is included in the genus Morbillivirus. Envelope has two lipoprotein spikes of haemagglutinin and fusion protein. Haemagglutinin is responsible for attachment to the host cell while fusion protein causes fusion of 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 as a prodrome of fever, malaise, conjunctivitis, coryza followed by Koplik’s spots. They look like tiny white spots surrounded by a red ring and are seen on the inside of the cheek. This is followed by 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 or 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 the 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 will show characteristic multinucleated giant cells called Warthin- Finkeldey cells which are infected cells which have fused due to fusion protein. Viral antigens can also be detected by direct immunofluorescence. Tissue culture will show 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, it has H and F antigens on the envelope. Two antigens - V or viral antigen and S or soluble internal nucleocapsid antigen are complement fixing. The virus has a predilection for parotid glands, testes, ovaries and pancreas.

Clinical features: Typically seen in children in the winter months. It presents as 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: 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 fusion protein which causes syncytium formation. Infection is spread by respiratory droplets. It occurs in outbreaks in winter causing severe infection in infants while adults have a mild illness.

Clinical features: In infants it causes bronchiolitis, pneumonia and tracheobronchitis. In older children it causes URTIs and otitis media. It may cause a 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. 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

It 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 while 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.