L 8 Diploma Ortho and Corona - Tagged

Orthomyxoviridae Overview

  • Definition: Greek origin "myxa" meaning mucus

  • Members:

    • Influenza A: Causes pandemics and epidemics, infects humans and animals (e.g., birds, pigs)

    • Influenza B: Causes epidemics, infects only humans

    • Influenza C: Causes mild upper respiratory tract infections

Structure and Genome

  • Type: Negative-sense single-stranded RNA (-ve ssRNA)

  • Configuration:

    • Enveloped

    • Segmented genome with 8 segments

    • 10-11 proteins produced

    • Requires RNA polymerase (RNA pol) to infect host

Important Proteins

  • Hemagglutinin (HA):

    • Function: Binds to sialic acid, aids in fusion and entry, targeted for vaccine development

  • Neuraminidase (NA):

    • Function: Cleaves sialic acid for virus release and spread, targets for antiviral medications (Oseltamivir, Zanamivir)

  • M2 Protein:

    • Function: Acts as a proton pump, essential for uncoating of the virus, targeted by older antivirals (Amantadine) which are now less effective due to resistance

Viral Lifecycle

  • Entry: HA binds to sialic acid → endocytosis

  • Replication: occurs in the nucleus, utilizes host machinery, steals 5' cap from host mRNA to initiate transcription

  • Release: Virus buds from the plasma membrane acquiring HA and NA proteins to form a complete virus

Antigenic Changes

  • Antigenic Drift:

    • Results from errors in RNA polymerase during genome replication, contributes to seasonal flu

    • Affects both type A and B viruses

  • Antigenic Shift:

    • Involves genetic reassortment, occurs only in type A due to its segmented genome and ability to infect multiple host species

    • Associated with pandemic outbreaks

Historical Examples

  • 2009 H1N1 Pandemic:

    • Triple reassortment virus, resistant to Amantadine and Rimantadine

    • Highlight of the importance of understanding genetic shifts in virus evolution

  • Influenza Pandemics Timeline:

    • Key occurrences include: 1918 H1N1, 1957 H2N2, 1968 H3N2, 2009 H1N1 (swine flu)

Pathogenicity and Symptoms

  • Infection Sites: Upper and lower respiratory tracts

    • Destroys mucus-secreting and ciliated cells, leading to increased susceptibility to secondary bacterial infections

  • Symptoms: Abrupt onset (1-4 days incubating) including fever, cough, body aches, fatigue, vomiting and diarrhea (more common in children)

Immune Response

  • Interferon and Cytokine Response: Crucial for controlling infection

  • Strain Specificity: Immunity against HA and NA is strain-specific; reinfections with different strains are common

Treatment and Vaccination

  • Antiviral Medications: Oseltamivir and Zanamivir inhibit NA, must be used early

  • Vaccination: Includes inactivated vaccines (grown in eggs) and live attenuated vaccines (cold-adapted)

  • Annual Vaccinations Recommended: All individuals encouraged to vaccinate due to widespread impact on health

Laboratory Diagnosis

  • Tests include cell culture, Hemagglutination tests for virus presence, Serology, and RT-PCR for strain identification

Risk Populations

  • High-risk groups: Elderly, young children, immunocompromised, pregnant women

  • Annual mortality in the U.S. ranges from 3,000 to 49,000

Conclusion on Influenza

  • Influenza virus poses significant public health issues due to its capacity for rapid mutation and reassortment, leading to seasonal outbreaks and sporadic pandemics.