Week 5 Magic Bullets
5.3 RESPIRATORY VIRUSES
1. Outline the major groups of viruses infecting the respiratory system, including influenza,
paramyxoviruses, rhinoviruses, coronaviruses and adenoviruses.
Viruses are obligate intracellular parasites. The most fundamental characteristic of a virus is that it is
absolutely dependent on a living host (cell) for its reproduction.
Virus Family
Orthomyxovirus
Paramyxoviridae
VIRUS
Influenza A, B, C
(RNA virus)
Respiratory
syncytial virus
(RNA virus)
VACCINES
LOCATION
AFFECTED
CLINICAL
SIGNS
Adenoviridae
Coronaviruses Adenoviruses
(cause 15%
(DNA virus)
common colds)
(RNA virus)
Adults, children,
elderly, immunecompromised,
elderly with
cardiac and
respiratory
problems at risk
Ubiquitous:
global
pandemics, local
epidemics. More
common in
winter
Infants, children
(most common
cause of RT
infection in
children), adults
All ages
All ages
coming into
contact with
animal carriers
Ubiquitous
Incidence
seasonal
Disease more
common in
early autumn,
late spring
Disease more
common in
winter, early
spring
Ubiquitous, no
seasonal
incidence
Influenza A + B
vaccine
(annually)
Antiviral drugs
(eg amantadine)
URT, LRT (others
outside RT)
No vaccines.
Antiviral drugs
No vaccines.
Antiviral drugs
for infants
No vaccines
Live,
attenuated
vaccine.
Respiratory tract,
most commonly
LRT
URT
URT, LRT (also
affect eye, GIT)
Sore throat,
cough, nasal
congestion.
Systemic: muscle
aches, fever,
chills, malaise,
Most commonly
in children:
Bronchiolitis,
pneumonia
Adults: generally
common cold
symptoms.
Mostly limited
to URT,
replicate in the
nasopharynx
Common cold,
major factor in
asthma
exacerbations.
Common cold
(afebrile),
SARS.
Infants:
associated
with
gastroenteritis
Febrile.
Bronchitis,
common cold,
sore throat,
conjunctivitis,
diarrhoea,
pneumonia
particles
(small) eg
sneezing. Widely
spread by school
children
DISTRIBUTION
OF VIRUS
Coronaviridae
Rhinovirus
(most common
cause of the
common cold)
(RNA virus)
Inhalation of large Inhalation of
aerosol droplets
droplets,
contact with
contaminated
hands
TRANSMISSION Airborne
RISK
FACTORS
Picornaviruses
Inhalation of
droplets,
contact with
contaminated
hands
Transmission
by aerosol,
close contact,
faecal-oral
route, or
fingers and
ophthalmologic
instruments
(eye infections)
Children, day
care centres,
military camps,
swimming
clubs.
Week 5 Magic Bullets
2. Identify the steps in the viral infection cycle with particular reference to infection of the
respiratory epithelium.
Respiratory Tract as site of entry
The respiratory tract in the most common route of entry for viruses. Other common sites of entry include
mucosal linings of the alimentary, and urogenital tract, the outer surface of the eye and the skin. The cell
imposes multiple barriers to virus entry. Viruses must overcome the mechanical barrier of the mucosal
lining. This mucosal lining traps microorganisms where they may be carrier to the back of the throat via cilia
and either coughed or swallowed (digested and degraded).
However, viruses exploit fundamental cellular processes to gain entry to cells and deliver their genetic cargo.
Virus entry pathways are largely defined by the interactions between virus particles and their receptors at
the cell surface. These interactions determine the mechanisms of virus attachment, uptake, intracellular
trafficking, and, ultimately, penetration to the cytosol.
Micro-organisms can avoid this by:
 Adhesions: specialised molecules, which enable binding to the receptor cell.
 The
Inhibiting
the action
of cilia.
Human
Respiratory
Tract
Mucus layer
Brush border
Most transmission via the respiratory tract occurs through sneezing and coughing which allows movement of
mucosal secretions. Increased nasal secretions that accompany many respiratory infections assist by
increasing the number of virus carrying droplets available to transmit the micro-organism.
1. Attatchment: The virus binds to the surface of the cell through adhesions.
2. Penetration: Fusion of the viral and host membranes, or uptake via a phagosome, results in the virus
carried across the plasma membrane and into the cytoplasm.
3. Uncoating: The viral envelope and/or capsid are shed and the viral nucleic acids released. At this point the
virus is no longer infective. Not until the virus has replicated and exits cell.
5. Transcription and/or translation.
4. Virus replicates: Viruses contain either DNA or RNA (never both). Viruses containing DNA, mRNA can
form using the host’s RNA polymerase. Viruses with only RNA must use their own RNA polymerases.
6. Assembly: Combining the replicated nucleic acid with newly synthesized capsomeres.
7. Release: Exit from the host cell.
Week 5 Magic Bullets
The epithelium may be left compromised. For example in a rhinovirus the DNA is replicated within the
cytoplasm and exists via cell lysing instead of budding. This results in epithelial damage, and thus prone to
secondary infection. This was seen in Mrs A’s case in Magic Bullets.
3. Identify the location in the respiratory system typically infected by these agents, and the
clinical pattern invoked.
Upper Respiratory Infections: Common Cold, Sinusitis, Pharyngitis, Epiglottitis and Laryngotracheitis.
Most upper respiratory infections are of viral aetiology.
Common Cold
Aetiology: Common colds are the most prevalent entity of all respiratory infections. Rhinoviruses are the
most common pathogens. Coronaviruses, Parainfluenza viruses, respiratory syncytial virus, adenoviruses and
influenza viruses have all been linked to the common cold.
Pathogenesis: direct invasion of epithelial cells of the respiratory mucosa, but destruction and sloughing of
these cells or loss of ciliary activity depends on the specific organism involved. There is an increase in both
leukocyte infiltration and nasal secretions.
Clinical Manifestations: After an incubation period of 48-72 hours, classic symptoms of nasal discharge,
obstruction, sneezing, sore throat and cough. Myalgia and headache may also be present. Fever is rare.
Diagnosis: based on symptoms (lack of fever combined with symptoms of localization to the nasopharynx).
Prevention/Treatment: symptomatic- decongestants, antipyretics, fluids and bed rest. Avoid infecting
others, along with good hand washing, are best measures to prevent spread.
Sinusitis
Aetiology: Acute sinusitis is most often a secondary response to a primary URT infection of either a bacterial,
viral or fungal nature. (Chronic sinusitis - lasts minimum 8 weeks, bacterial origin).
Pathogenesis: Impair ciliary action of epithelial lining of sinuses, increased mucous secretions- obstruction
and impedes drainage. With bacterial multiplication in the sinus cavities, the mucus is converted to
mucopurulent exudates. The pus further irritates the mucosal lining causing more oedema, epithelial
destruction and obstruction.
Week 5 Magic Bullets
Clinical Manifestations: The paranasal sinuses (commonly maxillary, ethmoid) are implicated. Pain,
sensation of pressure and tenderness over affected sinus exists. Malaise and low-grade fever may occur.
Diagnosis: difficult to distinguish bacterial and viral sinusitis. If resolve within 10 days most likely viral, if
persist generally bacterial and antibiotics prescribed.
Pharyngitis
Aetiology: inflammation of the pharynx. Can be bacterial, viral (adenovirus, herpes simplex virus, EpsteinBarr virus and cytomegalovirus infections) and less commonly fungus.
Pathogenesis: viral pathogens invade the mucosal cells of the nasopharynx and oral cavity, resulting in
oedema and hyperemia of the mucous membranes and tonsils.
Clinical Manifestations: presents with a red, sore, scratchy throat. Inflammatory exudate may cover tonsils.
Vesicles or ulcers may be seen on the pharyngeal linings. Depending on pathogen, fever and systemic
manifestations such as malaise, myalgia, or headache may present.
Diagnosis: Serologic tests may be used to confirm due to viral, mycoplasmal or chlamydial pathogens.
Prevention/treatment: symptomatic treatment for viral pharyngitis. The exception is herpes simplex virus,
which can be treated with acyclovir if clinically warranted or if diagnosed in immunocompromised patients.
Lower Respiratory Infections: Bronchitis, Bronchiolitis and Pneumonia.
Although viruses can cause lower respiratory tract infections, most LRI are of bacterial aetiology.
Bronchitis and Bronchiolitis
Aetiology: respiratory syncytial virus primary cause in infants. Other viruses, including influenza viruses and
adenoviruses (as well as occasionally M pneumoniae) are also implicated.
Pathogenesis: Infants initially have inflammation and sometimes necrosis of the respiratory epithelium, with
eventual sloughing. Bronchial and bronchiolar walls are thickened. Exudate made up of necrotic material and
respiratory secretions and the narrowing of the bronchial lumen lead to airway obstruction.
Clinical Manifestations: bronchiolitis presents with a cough and fever is common. A deepening cough,
increased respiratory rate, and restlessness follow. Retractions of the chest wall, nasal flaring, and grunting
are prominent findings. Wheezing or actual lack of breath sounds may be noted, respiratory failure and
death may result.
Diagnosis: Aspirations of nasopharyngeal secretions or swabs are sufficient to obtain specimens for viral
culture in infants with bronchiolitis. Rapid serological diagnostic tests for antibody or viral antigens may be
performed on nasopharyngeal secretions.
Prevention/Treatment: Respiratory syncytial virus infections in infants may be treated with ribavirin.
Pneumonia
inflammation of the lung parenchyma, consolidation of lung tissue may be identified by physical examination
and chest x-ray.
Aetiology: viral pneumonias are rare in healthy adults (exception of pneumonia caused by influenza viruses).
A serious complication following influenza virus infection is secondary bacterial pneumonia, particularly s.
pneumonia. Respiratory syncytial virus can cause severe pneumonia among infants as well as among
institutionalized adults. Adenoviruses may also cause pneumonia. Measles pneumonia may occur in adults.
Pathogenesis and Clinical Manifestations: Infectious agents gain access to the lower respiratory tract by the
inhalation of aerosolized material, by aspiration of upper airway flora, or haematogenous seeding.
Pneumonia occurs when lung defence mechanisms are diminished or overwhelmed. The major symptoms or
pneumonia are cough, chest pain, fever, shortness of breath and sputum production. Patients are
tachycardia. Headache, confusion, abdominal pain, nausea, vomiting and diarrhoea may be present,
depending on the age of the patient and the organisms involved.
Microbiologic Diagnosis: Viral infection may be diagnosed by demonstration of antigen in secretions or
cultures or by an antibody response, or serologic tests.
Prevention/Treatment: Until organism identified, therapy based upon clinical history. Therapy is then
directed at the specific organism responsible.