Orthomyxoviridae and Paramyxoviridae Lecture Review

Orthomyxoviridae vs. Paramyxoviridae

  • Orthomyxoviridae:

    • Prefix meaning: "correct"

    • "Myxo" meaning: Mucus

    • Genome: Segmented (-) RNA

    • Key examples: Influenza A, B, C

    • Reassortment possible? Yes

  • Paramyxoviridae:

    • Prefix meaning: "beside/related to"

    • "Myxo" meaning: Mucus

    • Genome: Non-segmented (-) RNA

    • Key examples: Measles, Mumps, RSV

    • Reassortment possible? No

Orthomyxoviridae (Influenza)

  • Family of RNA viruses with a negative-sense ssRNA and a segmented genome allowing for gene reassortment.

  • mRNA is positive sense.

  • Causes respiratory infections with complications like pneumonia, bronchiolitis, sinusitis, croup, COPD, Reye’s Syndrome, myocarditis, myositis, or pericarditis.

  • Transmitted through aerosols, infected bird droppings, saliva, nasal secretions, feces, and blood.

  • Virions are labile and need hydration to survive; destroyed by detergent.

  • Key proteins:

    • Hemagglutinin (HA): Attachment and membrane fusion; binds to sialic acid receptors.

    • Neuraminidase (NA): Viral release and spread; glycoside hydrolase that breaks down mucins; cleaves sialic acid on surface for release.

    • M2: Protein channel; virus budding

  • Antigenic variation:

    • Antigenic Shift: Reassortment of HA and NA genes, leading to novel antigenic properties and potential pandemics; Segmented genome allows for reassortment of HA and NA genes; outcome- causes human epidemics/pandemics

    • Antigenic Drift: Point mutations in HA due to error-prone RNA polymerase, requiring new vaccines yearly; Error-prone RNA-dependent RNA polymerase; outcome- seasonal flu requires new vaccine each year

  • HA binds to sialic acid, with human influenza binding alpha2,6-linkage (H1N1- easily spread, rarely fatal) and avian influenza binding alpha2,3-linkage (H5N1- spreads slowly, often fatal).

  • Definitions:

    • Endemic: Normal yearly circulating virus.

    • Epidemic: Disease outbreak exceeding expectations in a region.

    • Pandemic: Epidemic spreading across a large region or worldwide.

  • Past pandemics: 1918 (H1N1), 1957 (H2N2), 1968 (H3N2).

  • Avian flu (H5N1) is a potential pandemic risk.

Paramyxoviridae

  • Includes parainfluenza, measles, mumps, and RSV; negative-sense ssRNA, non-segmented genome.

  • mRNA is positive sense.

  • Genome – Transcriptional Polarity utilizes a single promoter model.

Mumps

  • Clinical symptoms: Cold-like symptoms, fever, headache, swelling of parotid glands (parotitis).

  • Transmission: Highly contagious through respiratory droplets and direct contact.

  • Complications: Testicular inflammation, aseptic meningitis, encephalitis, ovarian inflammation, hearing loss (most common cause of acquired deafness in children).

  • Diagnosis: Physical examination of parotitis.

  • Prevention: Effective vaccine since the 1960s; treatment is supportive care.

Measles

  • Clinical symptoms: Cold-like symptoms, high fever, cough, runny nose, inflamed eyes, Koplik’s spots (small white spots), red rash.

  • Transmission: Respiratory droplets and aerosolization.

  • Complications: Diarrhea, bronchitis, otitis media, pneumonia, corneal ulceration, encephalitis, hearing loss, death.

  • Diagnosis: History of fever, cough, coryza, conjunctivitis, observation of Koplik’s spots, positive measles IgM antibodies, isolation of measles virus RNA.

  • Prevention: Effective MMR vaccine; treatment is supportive care.

  • Measles infects lung epithelial cells, hijacks immune cells, and spreads systemically, causing a cough and remaining airborne for 2 hours.

  • Measles has the highest "R_0 value

(R_0) Basic Reproductive Number

  • (R_0 < 1): Infection will die out.

  • (R_0 > 1): Infection will spread.

Measles Contagiousness and Danger

  • Measles temporarily suppresses the immune system, making children vulnerable to other infections.

  • Severe complications include pneumonia, encephalitis, severe diarrhea, and subacute sclerosing panencephalitis (SSPE).

  • Vaccination protects those who cannot be vaccinated, achieving herd immunity.

The surface proteins of influenza are Hemagglutinin (HA) and Neuraminidase (NA). HA is responsible for attachment and membrane fusion by binding to sialic acid receptors on host cells. NA is responsible for viral release and spread by breaking down mucins.

Antigenic drift is caused by point mutations in the HA gene due to error-prone RNA polymerase, which requires new vaccines yearly. Antigenic shift is the reassortment of HA and NA genes, which leads to novel antigenic properties and potential pandemics.

Orthomyxoviruses have a segmented (-) RNA genome, which allows for gene reassortment. Paramyxoviruses have a non-segmented (-) RNA genome and use a single promoter model for transcription called Transcriptional Polarity.

R_0 or Basic Reproductive Number, is the average number of new infections that a single infected individual will cause in a population.