Respiratory Viral

Infections
Orthomyxoviridae

• 3 genera; influenza A, B and C

• Types A and B – epidemic and pandemic (A)
• Influenza A – wide variety of vertebrate
hosts
• Influenza B and C – humans only

• Type A – moderate to severe illness, all

ages
• Type B – milder illness, primarily
children
• Type C – mild or asymptomatic, not
epidemic
 Influenza – Clinical features

Infection of respiratory tract

• Fever; 37.5-39.5 0C
• Cough
• Sore throat
• Headache
• Muscle aches (myalgia)
• Extreme fatigue
• Potential to cause pneumonia – life
threatening
• Significant morbidity and
mortality
Th‹• LIPID ENVE t0PE i‹ pi‹Lrd
up
Influenza virus Haemagglutinin (HA)

HA is a spike-shaped glycoprotein extending from the

surface of the virus

Two functions:
1. Recognition of target vertebrate cells via binding to
sialic acid-containing receptors
2. Once bound – facilitates entry of viral genome into
target cells by fusion of host endosomal membrane with
viral membrane
 Influenza virus – Neuraminidase (NA)

Neuraminidase enzyme – 4 identical subunits

arranged in a square conformation

Glycoside hydrolase enzymes – cleave

glycosidic linkages of neuraminic acid

Facilitate elution of progeny virus particles

from cell surface, prevent clumping and assist
in mobility of virus particles through
respiratory tract mucus
 Influenza antigenic changes

HA and NA antigens evolve over time

Changes due to:

Point mutations in the viral gene (antigenic drift)

Exchange of gene segment with another sub-type of Influenza

(antigenic shift)

Impact depends on extent of change

 Antigenic Drift

Occurs with A and B types

Example:

1997 – A/Wuhan/359/95 (H3N2) virus dominant

Late 1997 A/Sydney/597 (H3N2) appears, dominant by 1998

 Antigenic drift and influenza A

Antibody
Mutation

exposed To you were

en bodiee
recugn ze and attech HA antigens,
provgnlJng anachmonl ii ue
nf uenza an RNA virus,
and therefore prone to
mutation.

gene

antig
en

Antibodies

If the mulaiion causes lhe shape of the HA

antigen to change, zx›tibod‹es do not
recognize the virus and it csn infect Cost
Antigenic shift – Influenza A only

Example:

H2N2 circulating 1957-67

H3N2 appears in 1968 – completely

replaces H2N2
 Potential for reassortment in infected pigs…

Pig “mixing vessel”

e.g. pathogenicity of H5N1, transmission ability of H1N1

WHO/Animal surveillance – identify and reduce animal and public health

risks within national contexts
The genetic ckange that enables a flu strain to jump from
ene animal species to another including humans, is called •/ N›isE ric
sr ti r ›±
Antigenic shift can happen in three ways‹
 Pandemic Influenza A

year subtype pandemic deaths name

1889 H3 moderate 1 million Russian Flu

H1N1
1918 very severe 50 million Spanish Flu
(avian)

1957 H2N2 moderate 1-1.5 million Asian Flu

Hong Kong
1968 H3N2 moderate 0.75-1 million Flu

H1N1 18,500
2009 mild Swine Flu
(swine) lab confirmed
Respiratory Syncytial Virus

RSV first identified in 1955 as the cause of an

outbreak of coryza in a colony of
chimpanzees (chimpanzee coryza agent)

1957, isolated from infants with respiratory

illness;
renamed respiratory syncytial virus because it affects the respiratory tract
and causes giant cell syncytia in tissue culture

prevalent in young children - almost all children have been infected by 2 years of
age peak rates between 6 weeks to 6 months age

global annual infection rates of 64 million and mortality of 160,000

up to 25% - 33% of cases involve the lower respiratory tract, and 1% are severe
enough to necessitate hospitalization

RSV infections almost always occur in the winter, and occur every year
transmission by infected respiratory secretions – large droplet
and infected fomites rather than aerosols

highly contagious, incubation period 4 to 5 days

most important clinical syndromes caused by respiratory syncytial

virus are:
bronchiolitis
(50 – 90% of admissions) and pneumonia (5 – 40% of
admissions)in infants
croup and tracheo-bronchitis in young children
tracheobronchitis and pneumonia in the
elderly

infection localized to the respiratory tract where it induces

syncytia formation
pathologic effect of RSV mainly caused by direct viral invasion of the
respiratory epithelium followed by immunologically mediated cell injury

in bronchiolitis necrosis of the bronchi and bronchioles leads to the formation

of “plugs” of mucus, fibrin, and necrotic material within smaller airways and
the narrow airways of young infants are readily obstructed by such plugs

along with inflammation of bronchioles

formation of plugs leads to air trapping
and decreased ventilation.

low-grade fever, tachypnea,

tachycardia, and expiratory wheezes
over the lungs.

usually self-limiting, but may be

fatal in premature infants
– long term effects

both mild and severe RSV bronchiolitis may be followed by recurrent

wheezing for several years

it has been debated whether the recurrent wheezing is mainly a non-allergic

condition with a good long-term prognosis or an early onset of IgE-
associated asthma

evidence that severe RSV bronchiolitis in early infancy is a strong risk factor
for the occurrence of allergic asthma in early adolescence.

Severe Respiratory Syncytial Virus Bronchiolitis in Infancy and Asthma and Allergy at Age 13
Nele Sigurs, Per M. Gustafsson, Ragnar Bjarnason, et al.
Am J of Respiratory and Critical Care Medicine, Vol 171, 2005
prevention
active immunisation – vaccination

passive immunisation – immunoglobulin (humanised monoclonal – palizumab)

antivirals – aerosolized ribavirin

infection control is important in the prevention of hospital-acquired

infection hand washing
wearing gloves and gowns