EXAM: Influenza, Viral Receptors & Spikes, OmpathStudy

Influenza, Viral Receptors & Spikes, Interferons, and Viral Pathogenesis High-Yield Revision Notes Institution: Mount Kenya University — School of Medicine & Surgery Unit: MBMM 3300 — Medical Virology and Mycology Level: MBChB Year 3 --- Papers & Examinations Covered Exam Date Paper --- --- --- Main Exam January 2022 MBMM 3300 Paper 1 Main Exam February 2021 MBMM 3300 Paper 2 Main Exam July 2019 MBMM 3300 Paper 2 Main Exam January 2023 MBMM 3300 Paper 2 End of Term CAT December 2020 MBMM 3333 Medical Virology CAT II 2018/2019 MBMM 3233 Medical Virology --- Topics Covered Influenza Virus — structure, antigenic shift, antigenic drift, clinical features, treatment, vaccines Viral Receptors and Spikes — structure, function, clinical importance, examples Interferons — types, mechanism of action, antiviral role, clinical use Viral Pathogenesis — stages, mechanisms, persistent infections, host defenses --- --- Part 1: Influenza Virus 1. Introduction Influenza is an acute respiratory illness caused by Influenza viruses. It is one of the most clinically and epidemiologically important viruses in medicine, responsible for seasonal epidemics and occasional global pandemics. Its unique ability to change its surface antigens — antigenic drift and antigenic shift — is why it remains a major global health threat and why the influenza vaccine must be reformulated every year. At MKU, influenza is examined almost every year, primarily through the essay question on antigenic shift versus antigenic drift and their clinical significance. --- 2. Classification and Structure Family: Orthomyxoviridae Genome: Single-stranded, negative-sense RNA — segmented into 8 segments Enveloped virus Types: Influenza A, B, and C Influenza A — causes epidemics and pandemics; infects humans, birds, pigs Influenza B — causes epidemics; infects humans only; less severe Influenza C — causes mild illness; not clinically significant Surface glycoproteins — the two most important structures: Haemagglutinin (H or HA) Binds sialic acid receptors on respiratory epithelial cells Mediates viral attachment and fusion with host cell Target of neutralizing antibodies — antibodies against H prevent infection 18 subtypes identified (H1 to H18) Neuraminidase (N or NA) Cleaves sialic acid to release newly formed virions from infected cells Prevents viral aggregation Facilitates spread through mucus Target of neuraminidase inhibitor drugs 11 subtypes identified (N1 to N11) Internal proteins: M2 protein — ion channel; involved in uncoating; target of adamantane drugs Nucleoprotein (NP) — determines type (A, B, or C) RNA polymerase complex — error-prone; no proofreading; drives antigenic drift --- 3. Antigenic Variation — The Highest Yield Topic This is the single most important concept in influenza and has appeared as an essay question in multiple MKU past papers. Antigenic Drift — Minor Antigenic Change Definition: Small, gradual, cumulative changes in the H or N antigens caused by point mutations in the viral RNA during replication. Mechanism: The RNA polymerase of influenza has no proofreading ability Random point mutations accumulate in the genes encoding H and N Over time, the surface antigens change enough that existing antibodies no longer recognize them The immune system is partially but not fully effective against the new strain Clinical significance: Occurs continuously and gradually Responsible for seasonal influenza epidemics every year Explains why the influenza vaccine must be updated annually Affects both Influenza A and Influenza B Antigenic Shift — Major Antigenic Change Definition: Sudden, dramatic change in the H or N antigens resulting from genetic reassortment between two different influenza A strains infecting the same host simultaneously. Mechanism: Influenza A infects multiple species — humans, birds, pigs When two different Influenza A strains infect the same cell simultaneously (e.g., a human strain and a bird strain infecting a pig) The 8 RNA segments from each strain mix randomly during replication — reassortment A new hybrid virus emerges with a completely new combination of H and N antigens Human population has no pre-existing immunity to the new H or N subtype Clinical significance: Occurs suddenly and unpredictably Produces a completely new subtype that the human population has never encountered No existing immunity in the population Responsible for influenza pandemics Only affects Influenza A — because only Influenza A infects multiple species Historical pandemics caused by antigenic shift: 1918 Spanish flu — H1N1 — killed 50 million people 1957 Asian flu — H2N2 1968 Hong Kong flu — H3N2 2009 Swine flu pandemic — H1N1 (new reassortant) Key Comparison Feature Antigenic Drift Antigenic Shift --- --- --- Type of change Minor, gradual Major, sudden Mechanism Point mutations Genetic reassortment Viruses affected Influenza A and B Influenza A only Result New variant of same subtype Entirely new subtype Immunity Partial pre-existing immunit