1
Orthomyxovirus
Hugh B. Fackrell
Fackrel@Uwindsor.ca
Filename: orthomyx.ppt
4/13/2015
2
Orthomyxovirus Outline
Structure
Classification
Multiplication
Clinical manifestations
Epidemiology
Diagnosis
Control
Baron’s Web Site
4/13/2015
3
Structure
Influenza viruses
ssRNA, antisense,
multipartite genome, 7-8
segments, 10 genes
spherical OR filamentous
enveloped
 hemagglutinin
 neuraminidase
4/13/2015
4
Flu Hemagglutinin
Protein in viral envelope
13 different hemagglutinin antigens
binds to N-aceytlneuraminic acid on host
cell glycolipids or glycoproteins
Hemagglutinin hydrolysed by host cell
proteases to create infectious virion
4/13/2015
5
Flu Neuraminidase
Found in the viral envelope
9 different neuraminidase antigens
Removes N-acetylneuraminic acid from
glycolipids and glycoproteins derived from
host cell
Dissolves N-acetylneuraminic acid in
mucus to increase liquefaction
Prevents self hemagglutination
4/13/2015
6
Classification
Three antigenic types of nucleoprotein give rise
to three different strains of influenza
 Flu A,
 Flu
B
 Flu C
No antigenic cross reactivity of nucleoproteins
4/13/2015
7
Gene Reassortment
ANTIGENIC SHIFT
Host cell is infected simultaneously with
two different strains of flu
Progeny viruses have mixture of gene
segments because RNA multipartite
Novel Type A strains
gives rise to pandemics of
influenza A
4/13/2015
8
Influenza 1918
Started in midwestern USA
Spread to Europe on troopships
Attacked healthy adults
Antigenic Shift
Trying to isolate cells with both strains of
Virus
4/13/2015
9
Antigenic Drift
Flu A Flu B undergo genetic changes in the
enveloped proteins
MINOR antigenic changes
serologically cross reactive
Causes yearly epidemics
4/13/2015
10
Influenza Subtypes
Strain Influenza A
 first isolated Bangkok
 Year 79
Hemagglutinin :H1, H2, H3
Neuraminidase N1, N2
A/Bangkok/79 H3N2
Link to CDC Web site
4/13/2015
11
Flu
infection
cycle
4/13/2015
12
4/13/2015
13
“Original Antigenic Sin”
Individual develops antibodies to flu
antigens after first exposure
On second exposure antigens changed
inducing a new array of antibodies
Antibodies to shared antigenic epitopes
have higher avidity
Used to identify the original infection
4/13/2015
14
Influenza Multiplication
virus binds to host by hemagglutinin
transcription & nucleocapside assembly in
nucleus
infectious virions assembled in cytoplasm
bud from cell membranes
cycle takes 6 hours
4/13/2015
15
Clinical Manifestations
Respiratory symptoms
 Coryza, sore throat, cough,
substernal chest pain
Systemic Symptoms
 Headache, chills, fever (3840C), prostration
4/13/2015
16
Epidemiology
Epidemic lasts 6 weeks in Jan-Feb
First in school age children (5-9 years)
Brought home to preschooler & adults
 industrial
absenteeism
 Pneumonia influenza in elderly
4/13/2015
17
Diagnosis
Clinical symptoms
more likely if
 syndrome occurs in adults in winter
 a febrile respiratory epidemic is underway
Detection of Virus
 rise in antibody titre between acute phase and
convalescent phase
4/13/2015
18
Detection of Flu Virus
Isolated from respiratory secretions
 grown in tissue culture
 embryonated eggs
Virus identified by presence of
hemagglutinin
4/13/2015
19
Tissue culture
Hemadsorption
 Red cells adhere to virions budding from
the host cell
Hemagglutination inhibition
 Confirm
with serological analysis of tissue
culture fluid
4/13/2015
20
Prevention
Prevention
Influenza virus
vaccine
Treatment
Amantadine
 1976 effective
against type A Web
site
 Rimantadine

1993 effective against
type A & type B
Neuraminidase Inhibitors

zanamivir and oseltamivir
4/13/2015
21
Treatment
Amantadine
 1976 effective against type A Web site
 Rimantadine
 1993
effective against type A & type B
Neuraminidase Inhibitors
 1999 zanamivir and oseltamivir web Site
4/13/2015
22
Influenza virus vaccine
Developed half a century ago
virus grown in chick egg embryos
inactivated with formalin
One- doses administered pareenterally in
the fall
50-90% effective
Web site
4/13/2015
23
The national swine flu
immunization of 1976 was
accompanied by an increase risk
of Guillain-Barre syndrome
4/13/2015
24
Guillain- Barre Syndrome
AKA Acute Infectious Polyneuritis
Symptoms
 symmetric
flaccid paralysis
 facial paralysis
Degeneration of myelin of peripheral nerves
Allergic reaction
4/13/2015
25
Amantadine
Amantadine hydrochloride
administered for 10 days
blocks viral uncoating
prevents 50% of infections
prevents 67% of illnesses
prophylactically protects 80%
4/13/2015