Respiratory viral infections Flashcards
what is a communicable disease?
any disease that passes between people or animals
what % of all deaths by communicable disease are respiratory?
21%
do all respiratory viruses cause very severe diseases?
no, respiratory viruses cause diseases with a range of severity
name some viruses that cause the common cold
Rhinoviruses
Adenoviruses
Human Bocavirus 1 (a parvovirus)
Coronaviruses
These top 4 are routine causes of a mild common cold. Also:
Atypical bacteria – These often are able to infect following other infection events
- Mycoplasma pneumoniae
- Chlamydia pneumoniae
- Streptococcus pneumoniae
relationship between rhinovirus and the common cold
Rhinovirus belongs to the picornavirus family.
- single-stranded RNA
- over 100 different serotoypes, antigenically distinct from each other
- year-round infections but autumn and spring peaks
- Peak of virus levels coincides with symptoms
Do not spread to the lower respiratory tract since they replicate best at a few degrees below normal body temperature (33oC). Mainly confined to the nose. Rarely cause fever
No molecular diagnosis – “over one third” to “the predominant cause of the common cold”
Respiratory viruses beyond the common cold
Influenza viruses (Flu); types A and B
Paramyxoviruses
Respiratory Syncytial Virus (RSV) - biggest reason kids get hospitalised
Human Metapneumovirus (hMPV) Parainfluenza viruses 1 – 5 (PIV1 – 5) Rhinoviruses (new subtype C) Adenoviruses Coronaviruses
why can’t you grow viruses on a Petri dish?
because they are obligate intracellular parasites - have to grow inside cells
To identify, assume respiratory infection and isolate RNA from repiratory epithelia. Randomly sequence and most of the RNA will be patients. But if theres anything foreign report on that sequence and will say e.g. rhinovirus group C. Can even detect new pathogens
what varies between age groups?
The disease burden (hospitalisation) varies enormously between age groups
Infants are hospitalised by RSV, adenovirus and atypical rhinoviruses (serotype C)
Infants are rarely hospitalised by influenza
Hospitalisation by seasonal ‘flu is a feature of old-age
RSV infection also hospitalises the old (over 64s)
Rhinoviruses – now known to also often cause lower resp tract infection severe enough to hospitalise people
Influenza A really low
Respiratory Syncytial Virus (RSV)
- a type of paramyxovirus
- infection of the respiratory tract and lungs
- causes severe bronchiolitis
- main cause of infant hospitalisation
- wheezing/asthma in later life
- no vaccine, trials had to be halted in 1966
- expensive prophylactic treatment (Synagis®) estimated at $6,160 per child per season
- we are repeatedly infected, can hospitalise the old
- RSV is reasonably genetically stable, so reinfection implies we have a poor immune memory to it
why is immunity with RSV poor?
RSV is reasonably genetically stable, so reinfection implies we have a poor immune memory to it
We inherit some protective Ig by placental transfer
We make protective Ig in response to RSV, but this is a poor response in neonates. Despite repeated reinfection our Ig response (at least against the G protein) declines with age
T cell memory generated, but T cell memory not as good as antibody memory hence not protected for life-time
explain the immune response against RSV?
The Ig response to a primary infection is so poor that resolution requires cytotoxic (CD8+) T cells
and CD8+ T cells require Th1 CD4+ cells for help. The Th1 response in neonates is generally poor (takes about 2 yrs to make a proper TH1 cell), may be exacerbated by breast feeding
RSV infection is associated with Th0>Th2 polarisation, and inhibition of Th17 and Treg cells. This is an active immune evasion strategy by the virus which prolongs infection and leads to a poor T cell memory
what is highly polarised during the early stages of viral infection?
The development of CD4+ subsets
By sensing early on that this is a viral infection, the system is highly polarised to form TH1 cells, release of cytokines (IFN type 1 and 2) that inhibit TH2 formation and release of IL12 by AP to make TH1.
This is going to lead to anergic type response in the lung
Seasonal Influenza
People of all ages are infected, usually only a serious problem in the old or children with asthma
- Lower respiratory tract infection causing damage to lung epithelia and viral pneumonia, often secondary pneumonia
- Fever, often prolonged
- Neurological (headache, malaise)
- Myalgia (muscle pain)
- Infection generates powerful, long-live immunity
- This virus changes what it presents to the immune system
- Easy to vaccinate against if you know what’s coming
Influenza virus structure
16 serotypes of haemagglutinin (H1 – H16)
9 serotypes of neuraminidase (N1 – N9)
8 separate RNA molecules packaged
Influenza is a bird virus - many strains in birds, are gut infectors
Human flu, is currently H3N2 which is the common one that you are likely to get. Also swine flu, H1N1.
Immune responses to influenza virus infection
Induction of robust interferon responses
Activation of inflammation
CD8+ cell targets
Eventually neutralising Abs generated against HA and N proteins
Why have I had ‘flu more than once and why do I get it again and why doesn’t the vaccine protect me?
Antigenic drift - generates antigens that are inefficiently recognised by existing antibodies - BUT broadly neutralising antibodies still offer some protection
Any flu that has changed 1 amino acid may be able to avoid a robust immune response. It replicates to high levels, and being an RNA virus, its polymerase is really error prone (high mutation rate)
You can inocculate an animal with a particular type of flu, you will not get the same virus output, it will have changed.
Antigenic Shift
Genetic reasortment leading to mixing of Heamagglutinin and neuraminidase to make a new virus
e.g. Animal infected with 2 different strains, happens all the time in pigs, pig farms are so badly manages and unhygienic - H1N1 and H2N2
Avian H5N1 deaths shows a bias - in what way?
an age bias in distribution
-older people are not dying from it, but it seems like when young, the immune response overactivates -> immunopathology. cytokine storm, immune response causes the disease
HOWEVER
seems to be poorly transmissible between people (if at all)
possibility of intermediate host transmission (notably cats)
what happened in 1968?
a change in a major protective antigen of influenza, hemagglutinin (HA) - altered the type of flu virus that new birth cohorts first encountered in life
Severe Acute Respiratory Syndrome
SARS
Epidemic lasted from November 2002 to June 2003 with 8,096 known cases of the disease, and 774 deaths (9.6% mortality)
A coronavirus; no existing immunity in humans!
Transmitted by droplets, causes severe respiratory disease
Transmitted from Civet cats!
Civets in turn got it from bats!
The SARS epidemic was ended by luck not by judgement - symptoms showed up long before virus shedding - main route of virus shedding is through feocal material that gets aerosolised
The “new” SARS
1,557 cases, including 648 deaths
Spreads from human to human (but not as well as SARS)
It’s not the same virus (now called MERS)
It IS a coronavirus
Its closest relatives are insectivorous bat coronaviruses…
Intermediate host appears to be camels and/or goats
antigenic shift vs drift
Antigenic drift is the slow accumulation of mutations in the genome. Viral RNA polymerase doesn’t proofread, meaning Influenza has a high mutation rate. Mutations generated during viral replication cause Haemagglutinin and Neuraminidase modifications. Some mutations are lethal, causing virus death. Some mutations may be advantageous and they are selected for, as they produce viral antigens human antibodies can no longer neutralise, allowing immune response evasion. Natural selection causes an increase in viruses that express the modified antigens. Antigenic drift causes epidemics due to the lack of herd immunity.
Antigenic shift involves viral gene reassortment, resulting in the emergence of a new viral strain. It can occur in Influenza because of its segmented genome. 2 viral strains co-infect a host cell, leading to genome recombination and new arrangements of genes coding for new viral antigens. Antigenic shift causes pandemics because the population is immunologically naïve against the new strain.
what is the effect of antigenic shift/drift on influenza spread and vaccines
The immune system will not recognise it, antibodies will not be able to bind to the viral antigens, so transmission occurs easily between people.
Viral shedding prior to symptom onset means Influenza is unknowingly spread to people in close contact, and the production of new viral strains are hard to predict and cause regular vaccine updates due to resistance.
