Untitled
ORTHOMYXOVIRUS
INTRODUCTION TO MYXOVIRUS
Myxovirus refers to enveloped RNA viruses characterized by their affinity for mucoprotein receptors on erythrocytes, causing hemagglutination.
These viruses are classified into two groups:
Orthomyxovirus
Paramyxovirus
The name "myxovirus" is derived from their tendency to adhere to mucins in host tissues.
ORTHOMYXOVIRUS: INFLUENZA VIRUS
Influenza Virus is an acute infectious disease affecting the respiratory tract associated with:
Forms: Occurs in sporadic, epidemic, and pandemic forms.
Classification: Divided into three serotypes: A, B, and C based on antigenic characteristics of:
Internal ribonucleoprotein (RNP) antigens
Matrix (M) protein antigens.
INFLUENZA VIRUS CLASSIFICATION
Influenzavirus A: Contains strains affecting both humans and animals.
Influenzavirus B: Exclusively contains human strains.
Influenzavirus C: Includes viruses from humans and swine.
MORPHOLOGY OF INFLUENZA VIRUS
Spherical Shape: Diameter ranges from 80 – 120 nm, capable of filamentous forms extending several micrometers.
Visibility: Certain strains can be seen using a dark ground microscope.
Core Structure: Composed of ribonucleoprotein arranged in helical symmetry.
Genome: Single stranded RNA, segmented into eight distinct pieces.
Viral RNA-dependent RNA polymerase: Essential for RNA transcription in host cells.
Envelope Structure: Contains an inner membrane protein layer and an outer lipid layer derived from the host cell membrane during the viral budding process.
M Protein: Composed of components M1 and M2, influences envelope interactions.
Viral Replication: Occurs in the nucleus of infected cells.
ENVELOPE SPIKES (PEPLOMERS)
Hemagglutinin (HA): Triangular spikes responsible for hemagglutination.
Neuraminidase (NA): Mushroom-shaped peplomers, less numerous, involved in viral spread.
STRUCTURE OF THE GENOME
Components:
Hemagglutinin (HA)
Neuraminidase (NA)
Nucleocapsid protein (NP)
Ion channel protein (M2)
RNA polymerase complex (PA, PB1, PB2)
Matrix protein (M1)
Non-structural proteins (NS1, NS2)
VIRAL PROTEINS
Detailed descriptions of viral proteins along with their:
Size (in amino acids):
Function:
Length of corresponding RNA segments:
| Protein | Size (aa) | RNA Length (nucleotides) | Function |
|--------------|-----------|-------------------------|------------------------------------------------------------------------------------------------|
| PB2 | 759 | 2341 | Binds to cap structures on pre-mRNAs, part of transcriptase complex. |
| PB1 | 757 | 2341 | Cleaves pre-mRNAs to create primer; responsible for RNA polymerase activity in transcription. |
| PB1-F2 | 87-90 | 2233 | Localized in mitochondria, enhances apoptosis in immune cells. |
| PA | 716 | 1778 | Component of transcription/replication complexes; exact role unclear. |
| HA | 566 | 1565 | Major surface glycoprotein, receptor-binding, facilitates viral fusion, antigenic determinant. |
| NP | 498 | 1413 | Binds and encapsidates viral RNA; regulates RNA synthesis functions. |
| NA | 454 | 1027 | Major surface glycoprotein; facilitates receptor destruction and dissociates virus aggregates. |
| M1 | 252 | 890 | Matrix protein that interacts with the envelope and nucleocapsids. |
| M2 | 97 | 230 | Integral membrane protein; functions in ion channel activity essential for uncoating. |
| NS1 | 230 | 121 | Down-regulates mRNA processing, suppresses RIG-1 signaling and interferon induction. |
| NS2 | 121 | - | Directs nuclear export of viral nucleocapsids, interacts with M1. |
VIRAL CELL ENTRY AND REPLICATION MECHANISM
Steps:
Attachment and Entry: The virus attaches to host cells.
Replication: Viral RNA is replicated in the host cell cytoplasm.
Assembly and Release: Newly formed virions are assembled and released from the host cell.
RESISTANCE OF INFLUENZA VIRUS
Heat Inactivation: Inactive at 50° C for 30 minutes.
Viability: Remains viable at 0° - 4° C for about a week, can be preserved at -70° C for years or through freeze-drying.
Chemical Disinfectants: Ether, formaldehyde, phenol, heavy metal salts destroy the infectivity; iodine is particularly effective.
HEMAGGLUTINATION
Characteristic of Influenza Virus: The virus interacts with fowl erythrocytes, leading to hemagglutination.
Process: Virus adsorbs to mucoprotein receptors, linking adjacent cells.
Peplomers: Hemagglutinin peplomers facilitate this interaction.
Elution: After a period, the virus detaches from the cell surface initiated by neuraminidase which destroys cell receptors by cleaving N-acetylneuraminic acid.
ANTIGENIC STRUCTURE
Classification: Antigens are either internal or surface antigens:
Internal Antigens: Ribonucleoprotein (RNP) known as soluble (S) antigen detectable via complement fixation and immunoprecipitation.
Type Specific: RNP does not exhibit significant antigenic variation.
Surface Antigens (V Antigen): Comprises hemagglutinin and neuraminidase, type-specific antigens also detectable by complement fixation tests.
HEMAGGLUTININ
Structure: Glycoprotein composed of two polypeptides, HA1 and HA2, responsible for:
Hemagglutination and hemadsorption.
Adsorption to mucoprotein receptors on red cells and respiratory epithelial cells.
Antibody Production: Antihemagglutinin antibodies develop post-infection/immunization; protective by blocking virus adsorption.
Variability: Hemagglutinin exhibits strain-specific antigenic variation with 15 identified subtypes (H1 to H15), with H1-H3 and H5 found in humans.
NEURAMINIDASE
Function: Glycoprotein enzyme cleaves cell receptors to aid viral release.
Immune Response: Anti-neuraminidase antibodies occur post-infection/immunization but are less effective than antihemagglutinin antibodies.
Subtypes: Nine subtypes identified (N1 to N9), susceptible to antigenic variation.
ANTIGENIC VARIATION
Definition: The ability of influenza virus to change antigenically, especially prominent in:
Type A: Highest variability.
Type B: Moderate variability.
Type C: Minimal variability.
Stable Antigens: Internal RNP and M protein remain relatively stable.
Surface Antigen Variation: Hemagglutinin and neuraminidase can undergo two types:
Antigenic Drift: Minor gradual changes due to mutations, leading to periodic epidemics (every 2-3 years).
Antigenic Shift: Dramatic changes through gene reassortment, often linked to new pandemics.
REASSORTMENT
Description: Coinfection by different strains leads to gene segment mixing, potentially resulting in hybrid strains.
Impact: May cause significant changes in viral surface antigens impacting epidemiology and complicating vaccine development.
TRANSMISSION
Modes of Transmission:
Direct transmission through aerosol droplets.
Fomites: Contact with contaminated surfaces or hands.
Susceptibility: Children, particularly school-aged children, are the most significant spreaders of influenza.
EPIDEMIOLOGY
Global Infection: Influenza infections are widespread and vary in severity.
Incidence: Peaks during winter months; types A and B cause epidemics every 1-3 years while type C typically does not.
Type C Infection: Endemic but usually causes mild symptoms.
Impact of Antigenic Variation: Highest in type A leading to significant public health challenges.
IMMUNITY
Antibody Production:
Anti-hemagglutinin and anti-neuraminidase antibodies primarily IgA provide protective immunity.
The role of cell-mediated immunity is noted but not completely understood.
PATHOGENESIS AND CLINICAL FEATURES
Incubation Period: Ranges from 1 to 4 days.
Infection Process: Virus attaches to and infects epithelial cells in the upper respiratory tract, causing diverse symptoms like:
Fever, headache, myalgia, abdominal pain, vomiting.
Potential complications include pneumonia and myocarditis.
Type B associated with Reye's syndrome, particularly affecting young children.
Secondary Infections: Common bacterial infections follow the initial viral infection.
PATHOGENESIS SUMMARY
Infection Gateway: Virus enters via the respiratory tract, replicates in epithelial cells leading to respiratory tract damage.
Symptoms: Abrupt onset of fever, headache, myalgia, cough, and fatigue.
LABORATORY DIAGNOSIS
Specimen Collection: Throat swab, nasal washings, or gargles, ideally within three days of symptom onset.
Storage Conditions: If not processed immediately, store at 4°C or -70°C with antibiotic treatment to destroy bacteria.
Virus Isolation Methods: Can utilize eggs or monkey kidney cell cultures.
Inoculate 11-13 day old eggs to isolate the virus from amniotic and allantoic fluids.
Hemagglutination Testing: Determines strain types based on agglutination patterns with different cell types:
Type A: Agglutinate guinea pig cells only.
Type B: Agglutinate both guinea pig and fowl cells.
Type C: Agglutinate fowl cells only.
TREATMENT AND PREVENTION
Antiviral Drugs: Two main classes:
Neuraminidase Inhibitors: e.g. Zanamivir and Oseltamivir, reduce symptom severity when taken early after infection.
M2 Protein Inhibitors: e.g. Amantadine and Rimantadine.
Vaccination: Primary prevention method, includes:
Inactivated Vaccine: Contains both A and B antigens.
Live Attenuated Vaccine: Mimics natural infection.
Recombinant Vaccines: Use of genetically engineered components.
Hygiene Practices: Essential for prevention, includes:
Frequent handwashing, alcohol-based sanitizer use, avoiding touch of face, and surface disinfection.