Viruses Flashcards
Which are bigger, bacteria or viruses?
Bacteria (1μ) in comparison to viruses (20-220nm)
Give two main differences between bacteria and viruses
- Viruses only grow inside living cells
2. Viruses have no cell wall
Where does the assembly of viruses take place in a cell?
Can take place anywhere. Nucleus (herpes virus), cytoplasm (poliovirus) or cell membrane (influenza)
Give two methods of release of a virus from a cell
- Lysis of the cell (rhinovirus)
2. By exocytosis over time (HIV, flu)
There are 5 main ways that viruses cause disease. What are they?
- Damage by direct destruction of host
- Damage by modification of host cell structure or function
- Damage through ‘over-reactivity’ of the host as a response to infection
- Damage through cell proliferation and immortalisation
- Evasion of extracellular/ intracellular host defence (variability or persistence)
Rotavirus is an example of a virus that causes disease by modification of the host cell. How does it do this?
- Infects epithelial cells of small intestine (jejunum) and shortens and atrophies villi
- This means there is decreased SA for absorption
- Also limits production of digestive enzymes e.g. disaccharides
- Malabsorptive state in patient and produces hyperosmotic effect in the jejunum causing profuse diarrhoea
Are the majority of hep B infections symptomatic or asymptomatic?
Asymptomatic
Why do carriers of HBV show no clinical symptoms?
They maintain a steady state between virus replication in host cells and host cell response
- Limited but sustained viral replication
- Proliferation of hepatocytes due to oncogenic properties of HBV
- Natural hepatocyte regeneration
- Liver cell destruction by CD8+ T cells that recognise HBV proteins on cell surface as foreign
How many types of HBV virus are there and how many have oncogenic potential in humans?
70-80 types. Type 16 and 18 have oncogenic potential
How does HPV cause a cervical cell carcinoma?
HPV genome integration disrupts E2 viral gene protein (control lost) which prevents the control of E 6 and 7. These control two cell growth and proliferation suppressor proteins Rb (E7) and p53 (E6), leading to dysplasia and cervical cell carcinoma.
What can increase the chance of integration of HPV virus into genome?
Mutagenic agents such as nicotine
How do viruses evade host defences (at cellular level)?
a) Persistence/latency (carrier for rest of your life)
b) Cell-to-cell spread (evade extracellular responses eg Ab’s)
How do viruses evade host defence (at molecular/genetic level)?
a) Antigenic variability
b) Prevention of host cell apoptosis
c) Down regulation of interferon and other intracellular host defence proteins (most)
d) Interference with host cell antigen processing pathways
Outline the 5 stages of chicken pox
Macule, papule, vesicle (blister formation), pustule, scab
What are ‘cropping lesions’ and what virus do they relate to?
Are lesions at different stages of evolution on the same body part. Found in chickenpox
What virus causes chickenpox and what kind of virus is this?
Varicella zoster - is a herpes virus
What transmission rate does chickenpox have?
90%
How long before the onset of rash in chickenpox is an individual infectious?
2 days (normally when symptoms start)
How is chickenpox spread?
Airbourne (nasal pharynx replication)
-normally from face –> face contact or being in the same room for more than 15 mins
In what two groups of people is it important to try and prevent chicken pox?
Pregnant and immunosupressed
Looking at the rash, how can you distinguish between chickenpox and smallpox?
Chickenpox will divide in warm parts of the body (core), whereas small pox will divide in the cooler areas (extremities)
What doubles the risk for pneumonitis in a patient with chicken pox?
If they are a smoker/ have lung disease
What virus causes shingles?
Herpes zoster
Why does shingles occur?
After primary infection, herpes zoster remains dormant in dorsal root ganglia. Reactivation causes shingles
How would you treat pregnant women or immunocompromised patients if exposed to varicella zoster virus
- Prophylaxis with zoster-immune immunoglobulin (ZIG)
2. If they develop chicken pox, give aciclovir
What are the most common sites for shingles?
Lower thoracic dermatomes and opthalmic branch of trigeminal nerve
What is Hutchinson’s sign and what would you look out for if it were present
Shingles on the tip of the nose. Suggests opthalmic branch of trigeminal involved. This suggests there could be occular involvement as this nerve also supplies cornea. Look for ulcers. Can be sight threatening.
What are the 5 red flags in shingles?
- Young people
- Peripheral dermatome affected
- Multiple dermatomes involved
- Secondary dissemination (haemorrhagic, spread to whole body from one dermatome)
- HIV
If a pregnant mother develops chickenpox, in what trimester is it most likely to affect the baby?
1st trimester
If a pregnant mother develops chicken pox, what are the potential effects on the baby
Limb hypoplasia (underdevelopment), microcephaly, growth retardation, cicatricial skin scarring, visceral and ocular lesions
What enterovirus can often be mistaken for chickenpox?
Hand, foot and mouth
How is the rash in secondary syphilis different to that of chickenpox?
Often feels scaly and is not itchy
How does parvovirus B19 present?
‘Slapped cheek’
What does parvovirus B19 do?
Attaches to immature red cells and prevents maturation. Can cause anaemia and high output cardiac failure in foetus, and reticular rash and joint pain in adults.
How would you treat a herpes simplex rash on border of lip
Aciclovir
How does eczema-herpeticum occur and is it serious?
Medical emergency
Occurs when herpes simplex virus interacts with pre existing skin disesase (usually atopic dermatitis)
Do not mistake as impetigo
What is muluscum and is it serious?
Small spots, in children will usually go away themselves
What are 3 signs of Primary CMV (cytomegalovirus)
- Macular rash
2. Glandular fever like posterior lymphadenopathy
Clinical symptoms of measles, what do you look for to report?
- Macular rash - sparing of pressure points
2. Cough, cold (/fever), diarrhoea, conjuncitivitis
What kind of rash presents in dengue?
Fine, maculopapular rash on trunk between day 3 and 5
What pain do patients often complain from when suffering dengue?
Retro-orbital pain, bone pain, joint pain
What are the 3 stages of the HIV epidemic?
- Nascent (all groups including high risk <5%)
- Concentrated (prevalence in one or more group is over 5%)
- Generalised (>5% prevalence in general population)
50% of all new HIV infections worldwide occur in what age group?
15-24
In what ways can sexual transmission of HIV be reduced? (there are a lot)
- Condom use (80% reduction)
- Male circumcision (60% reduction)
- Microbicidal gel (39%)
- HAART (highly active antiretroviral therapy)
- PreP
- STI control
- PEPse
HAART generally isn’t used until individuals CD4+ count falls below what level?
<350
What ways can HIV be transferred to others?
- Blood
- Sexually
- Vertically
In what ways could transmission between those who inject drugs be reduced?
- Needle and syringe programmes
- Drug dependence treatment - opioid substitution
- Close compulsory drug detention and rehabilitation centres
- Management of TB and viral hep
If mother of unborn child is not on HAART for HIV, what is the percentage transmission rate to unborn child?
35%
If mother of unborn child is on HAART for HIV, what is the percentage transmission rate to unborn child?
<1%
If HAART is used in a couple, one of whom is infected, and one whom isn’t, what percentage reduction in transmission occurs? (serodisconcordant couple)
96%
Give 4 reasons why circumcision leads to a decrease in percentage transmission of HIV
- Reduces ability of HIV to penetrate due to keratinization
- Inner part of foreskin contains many Langerhans cells, that are prime targets for HIV
- Ulcers characteristic of some STI’s occur on foreskin, if less chance of acquiring ulcers, less chance of transmission
- Foreskin may suffer abrasions or inflammation during sex- could facilitate passing of HIV
What problems are there with delivery of antiretrovirals to those in developing countries?
- Some individuals aren’t aware they have it
- Adherence issues
- Co- morbidities
- Cost of drugs
- Delivery of drugs
- Clinical services to test and monitor, clinics, etc
- Stigma around clinics
Where is HIV most prevalent?
Sub- saharan Africa
What are the 3 goals of HIV testing?
1) Test has high specificity and sensitivity
2) Have treatment, care, support services when +ve
3) Prevent transmission
What are UNAIDS 90/90/90 goals?
Global target of:
- 90% of people living with HIV being diagnosed
- 90% of people diagnosed on ART
- 90% of people diagnosed with HIV on ART will be virally suppressed by 2020
What are the two main markers used to monitor HIV infection?
- CD4+
2. Viral load
Why is the rate of HIV in IV drug users in the UK fairly low?
Needle exchange programmes
What is the definition of ‘late’ HIV diagnosis?
If the CD4+ cell count is <350
What are the implications of ‘late diagnosis’ of HIV on the patient?
Ten-fold increased risk of death in first year of diagnosis
How does ART delivered to patients suffering from HIV affect the lifespan of individuals?
Have normal lifespan
How does ART affect the viral load of individuals with HIV?
94% viral load was undetectable
How do STI’s such as herpes and chlamydia affect the probability that an HIV infection will be passed on to a sexual partner?
Increase
- Herpes = ulcers which make easier to pass on
- Chlamydia = inflammation, which is what HIV is targeting
What does PEP stand for, and how long after exposure to HIV virus must this treatment be given and how long for?
Post Exposure Prophylaxis - must be given 72 hours after exposure. For 28 days
What type of sexual behaviour carries the highest risk of acquisition of HIV from an infected partner?
Receptive anal intercourse
Why didn’t AZT (the first HIV drug) not work efficiently?
Was a single drug. We know now that a combination of 3 must be used to prevent the virus from mutating
What should indicate to you that a diagnostic test should be done for HIV?
Indicators of immunosupressive disease/seroconversion
What is the issue with using recognised risk factors in deciding whether to test for HIV or not?
Patients may not admit to risk factors, but also may not be aware of the risks
What is the ‘window period’ in HIV?
3 months. Reality is most patients will show up within 4 weeks
Give 3 conditions that would indicate a HIV test could be done?
- Oral candida (and not on long term ab’s or steroids)
- Raised Ig
- Unexplained lymphadenopathy
- Unexplained weight loss
- Recurrent shingles in young people
- PUO
If mum with unborn child presents, unsure as to whether she has ever had chicken pox, but has a family member at home with it, how would you manage this patient?
- Give mum immunoglobulin
2. AB prophylaxis - acyclovere
How would you treat cytomegalovirus? Is this virus serious?
Gancyclovir - is life threatening
What is it most important in taking history from suspected dengue patient?
Foreign travel - Often SE Asia
At what point post infection with HIV is an individual most infectious?
First couple of weeks (huge viral load) - after around a month seroconversion begins and viral load decreases
Symptoms of a patient with HIV ? And when>
A month in (seroconversion) –> headache, fever, muscle pains, joint pains, swollen glands, sweats, diarrhoea, rash (ACUTE HIV SYNDROME)
What are the clinical signs of a patient in the latency phase of HIV?
Generally asymptomatic with persistent generalised lymphadenopathy
Are patients in the latency phase of HIV still infectious?
Yes
How long does the latency phase of HIV often last?
7 years
AIDS defining illnesses?
Fungal pneumonias - pneumocystis jirovecii pneumonia and cryptococcal pneumonia or recurrent bacterial pneumonia
Kaposi’s sarcoma (HHV-8) - purple nodules in mouth or skin
Histoplasmosis
Toxoplasmosis –> encephalitis
Crytosporidiosis (watery diarrhoea and stomach cramps)
CMV - issues with digestive tract
Criteria for diagnosis of AIDS?
- <200 CD4+ cells
or - Any of AIDS defining illnesses
How does HIV transport itself to lymph nodes to where it can replicate?
Memory cells, macrophage or dendritic cell (at mucous membrane)
What are the names of the two co-receptors on CD4+ cells that HIV can bind to?
CCR5
CXCR4
What are the names of the proteins on the envelope of HIV that can bind to receptors on CD4+ cells?
gp120
gp41
What is the purpose of gp120 glycoprotein on surface of HIV?
Binds to CD4 receptor on T helper cell –> conformational change
Then gp120 will pierce T cell membrane and allows fusing of membranes
What mutation gives resistance to HIV?
CCR5 Δ32
Through what surface does HIV invade it’s host? Give some examples
Mucosa - Vagina, mouth, throat, nose, tip of penis, rectum, digestive tract
Outline very briefly how HIV replicates
- Enters CD4 cell using gp120 and CCR5 receptor
- CD4 cell digests matrix and capsule of HIV virus
- Viral RNA –> Viral DNA using RT (random errors)
- Viral DNA –> double stranded DNA
- Integrase carries DS DNA into nucleus, cuts host DNA and allows HIV to insert into host chromosome
- RNA polymerase forms mRNA –> ribosome –> envelope protein and other viral proteins
- Assembly of new VIRION (budding)
How does HIV evade immune response?
V3 loop constantly changing due to RT poor proof reading
Give 5 ways in which HIV depletes CD4+ T lymphocytes
- Direct cytotoxicity of infected cell
- Activated CD4+ cells have a shorter life span
- Atrophy of thymus
- Fibrous lymph node
- Bystander cell killing (e.g. infected macrophage)
All HIV + women are offered what test on an annual basis?
Cervical smear - HPV Human papilloma virus
At risk of invasive cervical carcinoma
Recurrent candidiasis, shingles or oral hairy leukoplakia is commonly seen in the early symptomatic phase of what disease?
HIV
What is the most common AIDS defining illness?
PCP
All patients with TB require an additional test for what?
HIV
What are the 3 most common causes of CNS mass lesions in HIV?
- Cerebral toxoplasmosis
- Primary CNS lymphoma
- Tuberculoma
What are the 3 most common causes of meningitis in HIV patients?
- Cryptococcal
- Tuberculous
- Pneumococcal
What are the 3 most common causes of opthalmic lesions in HIV?
- CMV
- Toxoplasmosis
- Choroidal TB
Give the 3 most common HIV related neoplasms
- Lymphoma (often diffuse large B cell NHL)
- Cervical neoplasia
- Kaposi’s sarcoma (HHV-8)
What is Kaposi’s sarcoma ?
Rare form of cancer caused by HHV-8. It is a tumour of vascular and lymphatic endothelium that presents as purple nodules and plaques
