Influenza Flashcards
Influenza
Family orthomyxoviridae
outbreaks annually
3 types- Influenza A,B,C
A — antigenically highly variable— epidemic influenza
B— may exhibit Ag changes and sometimes epidemics
C— antigenically stable— mild illness
Morphology of influenza
Virion- DNA dependent RNA polymerase
spherical shaped
Nucleocapsid- helical
Envelope—lipoprotein envelope with 2 spikes haemagglutinin HA and Neuraminidae NA
Genome— segmentedsingle stranded RNA virus
8-AB, 7-C
Proteins- 9 structural pr and 1 non structural pr
NP PB1 PB2 PA M1 M2 HA NA NS2
Structural pr and their functions
NP + RNA — RNP— helical — nucleocapsid
PB1 PB2 PA— bound to RNP — RNA transcription and replication
M1— morphogenesis and major component of virion- shell underneath envelope
M2— ion channel pr
NS2— in envelope
HA and NA( virus encoded glycoprotein)— important antigens that determine antigenic variations of influenza virus and host immunity
Reaction to physical and chemical agents of influenza
Relatively hardy
Destroyed by ether formaldehyde lipid solvents
Antigenic properties of influenza
Group-specific antigens
• Two internal ribonucleoproteins: nucleocapsid (NP) & matrix (M) distinguishes influenza into 2 types - A, B and C virus.
- Type specific antigens
• Hemagglutinin (HA) & Neuraminidase (NA) on surface
• Frequent antigenic changes occur
• Antigenic variations in the surface glycoproteins, HA and NA, are used to subtype the viruses.
Only type A has subtypes.
Humans
- 4 HA (H1-H3, HS) & 2 NA (NI-N2)
Birds, animals or humans
- 15 HA (H1 - H15) & 9 NA (NI-N9), in many different combinations
Outstanding characteristics of Influenza
Genetic reassortment
• Because of segmented nature of genome, when a cell is confected by 2 different influenza viruses result in mixtures of parental gene segments may be assembled into progeny virions
• Changes in antigenicity of haemagglutinin & neuraminidase (especially influenza A)
causes worldwide epidemics.
• sudden changes in surface antigens — epidemiologic features of influenza and significant problems for vaccines development
Two types of variations of influenza
Antigenic drift
• Minor antigenic changes, all three types of influenza virus exhibit antigenic drift.
* Due to point mutations in genome RNA, resulting in amino acid changes in the protein.
• Virion can escape recognition by host’s immune system due to altered antigenic sites on virus
Antigenic shift
• Major antigenic changes in HA or NA
• Drastic changes in sequence of viral surface protein result in appearance of new subtype
• Only influenza A virus undergoes antigenic shift
• The segmented genome of influenza virus A reassort readily in cells doubly infected by human & nonhuman influenza viruses (from birds, pigs and horses)
• Influenza virus B and C do not exhibit antigenic shift, perhaps because few related viruses exist in animals
Pathogenesis of influenza
MoT- airborne or contact
Few cells of res epithelium are infected
If virus avoid removal by cough reflex
Escape neutralization by IgA antibodies
Inactivation by Non specific inhibition in mucus
—progeny virion— spread to adjacent cells and replicate
Viral NA — lower viscosity of mucus film— promotes spread of virus containing fluid to LRT
many cells of RT are infected in short time and killed
Cellular destruction and desquamatio of superficial mucosa of RT
Do not infect basal epithelium
Secondary bac infectionStrep Staph H influenzae— 2’ pneumonia
Clinical findings of influenza
Uncomplicated influenza( chills headache dry cough high fever muscle aches malaise anorexia)
Children gi vomitting convulsions croup severe in <1yr otitis media
2’ Pneumonia s aureus, s pneumoniae, h influenzae
Reye syndrome encephalopathy in 2-16 yr
Lab diagnosis of influenza
Nasal washing
Throat swabs
Gargles
With 3 days of onset of symptoms
RT PCR
TISSUE CULTURE
HI
CFT
ELISA
RIA
Avian influenza
Do not undergo antigenic changes in birds
Genes caused previous influenza pandemics in humans remain unchanged in aquatic bird reservoirs
Ducks avirulent
Influenza virus muliply in intestinal tract and shed in feces into water
Avian flu Waterborne disease
Pig mixing vessels
H5N1 close contact with birds domestic poultry