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RESPIRATORY VIRUSES
What is a virus?
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Viruses are not cells. They cannot synthesise their own energy or proteins and are not capable of
independent replication. They are dependent on a host cell.
How do they differ from prokaryotes and eukaryotes?
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they are composed of an internal core containing DNA or RNA, not both. This is covered by
a protective protein coat. Some have an outer lipoprotein membrane (envelope). They do
not contain any organelles
Viruses can only reproduce within the host cell because they cannot synthesise energy or make
proteins
viruses do not replicate using the mechanisms of binary fission or mitosis. One virus can produce
hundreds more viruses. Refer to Lange (2008) p.192 for table
Viruses have varying shapes and sizes. The shape is determined by the repeating sub units that form
the protein coat called a capsid.
Nucleic Acid Make Up
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can be singe or double stranded DNA or RNA
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nucleic acid can be linear or circular
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DNA is always single molecule
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RNA can be single molecule or exist in several pieces
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the nucleic acid of the virus is surrounded by a protein coat (capsid)
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the capsid is made up of subunits called capsomes. In some viruses the capsid is the outer layer o
the virus. These are called naked viruses. In some viruses the capsid is surrounded by a lipoprotein
cover called an envelope, which becomes the surface of the virus.
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The capsomes and the nucleic acid form a structure called the nucleocapsid
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The repeating subunits of the capsid give the virus its shape and so is used when classifying viruses.
Spherical viruses are said to have icosahedral symmetry and others are said to have helical
symmetry.
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viruses that infect humans are helical and are enveloped.
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viruses only have one copy of their genome (haploid) except retroviruses (diploid)
Viral Proteins
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surface proteins help the virus attach to host cell receptors. This determines host specificity and
organ specificity of the virus.
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these surface proteins are the targets for antibodies. The antibodies bind to these surface protein and
prevent them from attaching to the cell receptor so inhibits (neutralises) viral infection.
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internal proteins can include DNA or RNA polymerase
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in enveloped viruses the matrix protein mediates interaction between viral nucleocapsid and
envelope proteins (surface protein)
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some viruses produce antigenic variants of surface proteins. This allows them to invade our
immune defenses because we may produce antibodies against one antigenic variant (serotype) but
not another
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Enveloped viruses acquire their envelope as they exit the host cell. This process is called budding
viruses that have an envelope are less stable as they are more easily inactivated. They are generally
more sensitive to heat, drying, detergents and lipid solvents such as alcohol.
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nearly all viruses transmitted via faecal-oral route are naked whereas viruses such as HIV, HBV
and HCV are enveloped and transmitted via blood or sexual transmission
Viral Growth Cycle
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One virion (1 virus particle) can replicate in approximately 10hrs to produce hundreds of virions
within that cell. Refer to Lange (2008) p.199 for growth curve.
when the virion enters the cell and infects it, it changes cell morphology and affects cell fx causing
a cytopathic effect (CPE) which results in cell lyses and death. Not all viruses cause CPE, some can
replicate and have little effect on changes to cell morphology or fx.
Stages of viral growth cycle (Lange 2008)
1. Attachment and penetration by parental virion
2. Uncoating of the viral genome
3. Early viral mRNA synthesis
4. Early viral protein synthesis
5. Viral genome replication
6. Late viral mRNA synthesis
7. Late viral protein synthesis
8. Progeny virion assembly
9. Virion release from cell
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Some viruses have surface proteins that attach to specific cells and or organs. E.g HIV attaches to
CD4 protein on T Helper lymphocytes
the virus enters the cell via pinocytotic vesicles which engulf it and takes it into the cell
the receptors for viruses on the cell have other normal fx. Eg. vaccinia virus binds to the receptor
for epidermal growth factor
All viruses are infectious but not all purified viral DNA or RNA (genomes) are infectious. If they
are infectious it means that they are able to replicate and carry out the entire viral growth cycle,
generating complete virus particles.
DNA viruses replicate in the nucleus.
RNA viruses replicate in the cytoplasm except retroviruses and influenza which partly replicate in
the nucleus.
RNA Viruses
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Categorised into 4 groups that differentiate how they synthesise mRNA
1. positive polarising single stranded RNA which uses its single strand as its genetic material.
Positive polarity is RNA with the same basic sequence as mRNA. Eg. if mRNA is ACUG, it
will ACUG
2. negative polarity single strand means mRNA must be transcribed by using the negative strand
as a template. Negative polarity is RNA with base sequence complimentary to mRNA Eg. if
mRNA is ACUG, it is UGAC
3. double stranded RNA. This virus carries its own polymerase to transcribe to mRNA
4. Single stranded RNA of positive polarity that is transcribed into double stranded DNA. This is
then transcribed to viral mRNA by host cell's regular RNA polymerase.
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Only viruses that do not require polymerase have infectious nucleic acid.
Major groups of viruses infecting the respiratory system
Influenza
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RNA virus, negative polarity genome, helical nucleocapsid, lipoprotein envelope
orthomyxovirus – segmented RNA genome. “myxo” means it interact with glycoproteins on the
surface of the cell.
smaller in size than paramyxoviruses
the envelope is covered with 2 different types of spikes
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haemogglutinin (H) its fx is to bind to cell surface receptor to initiate infection
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neuraminidase (N) its fx is to cleave neuraminic acid (sialic acid) to release progeny viruses
from the infected cell. It degrades the protective layer of mucus in the respiratory tract. This
enables it to infect the respiratory epithelium.
Influenza viruses especially influenza A can change in their antigenic variant of H and N proteins
contributing to their ability to cause epidemics.
Antigenic variation occurs because of:
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antigenic shifts – major changes in the re assortment of segments of genome RNA
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antigenic drifts – minor changes based on mutations in genome RNA
Influenza has 2 matrix proteins. M1 protein resides between internal nucleoprotein segments an
envelope and provides structural support. M2 matrix proteins form virion channels between the
interior of the virions and the external environment. M2 plays a role in allowing virions to uncoat
and allow the nucleocapsid to migrate into the nucleus of the cell.
Antigens on influenza are both group specific and type specific.
Internal ribnucleoprotein is group specific A,B,C
H and N are type specific and located on the surface
Antibodies against the H neutralises it and prevents infection by antibodies against the group do not
prevent infection
Antibodies against N do not neutralise it but helps to reduce disease.
Replication
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virion absorbed into cell when H interacts with sialic acid receptors
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virus uncoats within an endosome (vesicle formed during pinocytosis)
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protons pass through M2 protein into interior of virion. This frees nucleocasids to enter
cytoplasm and migrate into the nucleus
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replicates in nucleus
Transmission of influenza – airborne respiratory droplets
Infection is limited to upper and lower respiratory tract as the proteases that cleave the H are
located in the respiratory tract.
Signs and symptoms
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fever
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myalgia
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headache
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sore throat
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cough
Symptoms usually resolve within 4-7 days
Lab Dx – nasal or throat swabs, sputum, antibodies in serum
Treatment
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Amantadine – blocks M2 ion channels but in US 90% are resistant
Paramyxoviruses
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Measles, mumps, respiratory syncytial virus (RSV), parainfluenza virus
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differ from orthomyxoviruses because genome is not segmented
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surface spikes are different
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composed of one single stranded RNA helical nucleocapsid and outer lipoprotein envelope
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virion contains RNA polymerase which transcribes the negative polarity genome into mRNA.
Genome is not infectious
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envelope covered with spikes that contain H and N or a fusion protein that causes cell fusion or
haemolysis
Measles
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maculopapular rash, occurs mostly in childhood
has H and fusion protein that causes haemolysis
has single serotype (antigenic variant). Antibody is directed at H antigen
Humans are hosts
Transmitted via respiratory droplets – coughing and sneezing
after infecting cells of upper respiratory tract, it enters blood then to the skin
after rash appears, the virus can no longer be spread to others
life long immunity develops after the person has disease
Signs and symptoms
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fever
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conjunctivitis
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running nose
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coughing
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rash appears on face and proceeds down body to hands and feet
Treatment – no antiviral available
Immunisation with live attenuated vaccine.
Mumps
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Parotid gland swelling. Mostly in childhood
single serotype
antibody directed at H
transmitted via respiratory droplets
infects upper respiratory tract then spreads to blood then parotid glands, testes, ovaries, pancreas,
meninges
lifelong immunity occurs to those who have had the disease
Signs & symptoms
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fever
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malaise
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anorexia
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swelling of parotid glands (uni-lateral or bilateral)
Usually resolves within one week
No antiviral treatment
Immunisation with live attenuated vaccine
Respiratory Syncytial Virus (RSV)
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cause of pneumonia and bronchitis in infants
causes otitis media in children
causes pneumonia in elderly and people with chronic cardiopulmonary disease
surface spikes are fusion proteins that cause cells to fuse forming multinucleated giant cells
(syncytia)
2 serotypes A and B
Antibodies target fusion protein
Similar transmission to measles and mumps
RSV causes common colds and respiratory tract infections in normal adult population
No vaccine available
Parainfluenza Virus
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causes croup, laryngitis, bronchiolitis and pneumonia in children. In adults resembles colds
surface protein contain H, N and fusion proteins
Humans and animals are infected but animal strains do not infect humans
transmitted via same path as other paramyxoviruses
can cause croup in children under 5 – harsh cough and hoarseness
no antiviral or vaccine
Coronaviruses
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Causes common colds
non segmented single stranded RNA
helical nucleocapsid, enveloped
2 serotypes
SARS is an example
Replication
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absorbed into the cell via H. Enters into cytoplasm. Positive strand genome is translated to 2
large polypeptides which are self cleaved by virus encoded protease
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the virus is assembled and obtains its envelope from cytoplasmic reticulum. Replication
occurs in the cytoplasm
Transmitted via respiratory aerosol
Coronaviruses are limited to mucosal cells of the respiratory tract
immunity following infection appears brief and reinfection can occur
Pneumonia caused by SARS is characterised by oedema then hypoxia.
Signs and Symptoms
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running nose
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scratchy sore throat
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low grade fever
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typically lasts several days
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may cause bronchitis
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SARS is atypical
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fever from 38 degrees
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non productive cough
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dyspnoea
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hypoxia
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chills
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rigors
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malaise
sore throat and running nose uncommon
No antiviral or vaccine available
SARS has been experimentally treated with ribavirin and steroids however ???? effectiveness.
Adenoviruses
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Naked icosahedral viruses with double stranded linear DNA
causes pharyngitis, URTI and LRTI
PBL – Magic Bullets
What caused this lady to be susceptible to bacterial pneumonia?
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She had a viral infection which left her immunosupressed
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Her mucus membrane in the respiratory tract was already attacked by the virus previously and
leaves it open to strep. pneumoniae bacteria
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being in hospital caused hospital acquired pneumonia (nocosomial) pneumonia.