Viral & Prion Pathogens Flashcards
1
Q
What are the main characteristics of viruses?
A
- They are simple micro-organisms
- They are NOT capable of independent existence
- They need a host cell in order to survive e.g. red blood cell
2
Q
How do viruses use host cells to replicate?
A
they ‘steal’ energy, metabolic intermediates and enzymes from host cells in order to replicate
they may kill the cell in the process
3
Q
What are the components of the virus particle?
What 2 components are present in all viruses?
A
ALL viruses have:
- a genome - RNA or DNA
- capsid - protein coat
Some viruses have:
- envelope - lipid bilayer
- some viruses carry their own enzymes
4
Q
What are the 6 stages in the virus life cycle?
A
- Adsorption
- Penetration
- Uncoating
- Synthesis
- Assembly
- Release
5
Q
What is meant by the ‘adsorption’ stage in the viral life cycle?
A
Interaction between the host receptor molecule and the virus ligand
this determines the host-specificity of the virus
6
Q
What is meant by the ‘penetration stage’ of the viral life cycle?
A
Receptor-mediated endocytosis or, in some enveloped viruses, membrane fusion occurs
7
Q
What is meant by the ‘uncoating’ stage of the viral lifecycle?
A
Nucleic acid is liberated from the phagosome (if endocytosed) and/or capsid by complex enzymatic and/or receptor-mediated processes
8
Q
What is meant by the synthesis stage of the viral life cycle?
A
Nucleic acid and protein synthesis are mediated by host and/or viral enzymes
these take place in the nucleus or cytoplasm, depending on the specific virus
9
Q
What happens during the assembly stage of the viral life cycle?
A
Assembly of virus components is mediated by host and/or viral enzymes
10
Q
What occurs during the release stage of the viral lifecycle?
A
Complete virus particles are released by budding of host cell membrane or disintegration of host cell
11
Q
In what 2 ways are viruses classified?
A
Viruses are classified according to:
1. the genetic material inside them:
- DNA or RNA
- single or double stranded
- if single stranded - is the RNA positive or negative sense
2. Presence or absence of an envelope
12
Q
How can DNA viruses be classified?
What are examples of viruses in each category?
A
DNA viruses can be double-stranded or single-stranded
Double stranded:
- can be enveloped - Herpes viruses and Hepatitis B
- can be unenveloped
Single stranded:
- can only be unenveloped e.g. parvovirus
13
Q
How can RNA viruses be classified?
What are examples of each category?
A
14
Q
What type of viruses are herpes viruses?
What is a significant characteristic that they are characterised by?
A
They are double-stranded enveloped DNA viruses
they are characterised by their ability to establish latency and reactivate
(Once infected, it remains inside the body forever)
15
Q
How many types of Herpes viruses are known to infect humans?
A
9 types are known to infect humans
The 5 most common are:
- Herpes simplex 1
- Herpes simplex 2
- Varicella zoster
- Epstein Barr
- Cytomegalovirus
16
Q
What are other common names of Herpes simplex 1?
What is the epidemiology like?
A
HSV-1, ‘cold sores’
It exists worldwide and 80% of the UK population experience HSV-1 in their lives
17
Q
What is the mode of transmission of HSV-1?
A
- Direct contact with vesicle fluid from lesions
- Latency in sensory nerve ganglia - trigeminal nerve ganglion
- It has periodic reactivations
18
Q
What are the important clinical syndromes associated with HSV-1?
A
Vesicles/ulcers:
- these affect the skin or mucous membranes
- they are typically seen in the mouth
Encephalitis:
- this is brain inflammation
- HSV-1 is the commonest cause of viral encephalitis
19
Q
What are the alternative names for Herpes simplex 2?
What is the epidemiology like?
A
HSV-2, ‘genital herpes’
It exists worldwide and 10-20% of the population will experience infection in their lifetime
20
Q
What is the mode of transmission of HSV-2?
A
- Direct contact with vesicle fluid from lesions
- Latency in sensory nerve ganglia - sacral ganglia
- Periodic reactivations
21
Q
What are the important clinical syndromes associated with HSV-2?
A
Vesicles/ulcers:
- affect the skin and mucous membranes
- typically affect genitals/buttocks
Meningitis:
- often follows an outbreak of genital lesions
Neonatal herpes:
- occurs through vertical transmission from mother’s genital tract at birth
- causes severe disseminated viraemia (life threatening)
22
Q
What is meant by viraemia?
A
viruses entering the bloodstream and travelling around the body
23
Q
What are the 2 disease names of Varicella zoster virus?
What is the epidemiology like across the world?
A
Primary infection:
- this is the FIRST infection with the virus
- this causes chicken pox
Reactivation:
- any subsequent infections cause ‘herpes zoster’ or ‘shingles’
Epidemiology:
- 95% have had chickenpox by age 20 in UK
- In the tropics, this decreases to 50% due to changed climate
24
Q
What is the mode of transmission of varicella zoster virus?
Does it have a latency phase?
A
- Respiratory droplet from a person with chicken pox e.g. cough, sneeze
- direct contact with the vesicle fluid from a person with chicken pox or shingles
- latency is established in the dorsal root ganglion of the whole CNS
25
What are the important clinical syndromes associated with Varicella zoster virus?
**Chicken pox:**
* febrile illness with widespread vesicular rash
**Shingles/herpes zoster:**
* reactivation causing unilateral vesicles in a **dermatomal distribution**
* the rash only appears in one particular dermatome
26
What are the alternative names for Epstein Barr virus?
What is the mode of transmission?
‘Glandular fever’ or ‘infectious mononucleosis’
These names describe the symptoms and NOT the disease
it is called ‘kissing disease’ as the virus is shed in **saliva and genital secretions**
27
What is the main clinical syndrome associated with Epstein Barr virus?
What cells are involved?
**Infectious mononucleosis** - this is the primary infection
tonislitis, fever, lymphadenopathy, hepatosplenomegaly
it involves **atypical lymphocytes** (which look like monocytes)
80-90% of clinical infectious mononucleosis is caused by EBV
28
Where does Epstein Barr virus have its latency phase?
When is it reactivated?
It is reactivated from latency in **B cells**
It is reactivated when someone is **unwell** or **immunosuppressed** (e.g. solid organ or bone marrow transplant)
it is associated with **malignant B cell lymphoproliferative disorders**
29
What is meant by ‘lymphadenopathy’ and ‘hepatosplenomegaly’?
Lymphadenopathy - enlarged lymph nodes
hepatosplenomegaly - enlarged liver and spleen
30
What is the epidemiology of cytomegalovirus like?
% prevalence = age
(e.g. 20% of people will be infected by the time they are 20)
31
What are the modes of transmission of cytomegalovirus?
Where is its latency phase?
* Saliva or genital secretions
* donated blood, stem cells or solid organs
* Latency in **myeloid progenitors** of the immune system
* this includes monocytes and dendritic cells
32
What are the important clinical syndromes caused by cytomegalovirus?
**Infectious mononucleosis:**
* this is the primary infection and is the same as EBV
**congenital CMV infection:**
* in infants born to mothers who have the infection during pregnancy
* leads to retinitis, deafness, microcephaly and hepatosplenomegaly
33
When does CMV tend to be reactivated?
What happens when it is?
It is reactivated in **immunosuppressed patients** (e.g. transplant, advanced HIV)
reactivation of latent CMV can cause retinitis, colitis and pneumonitis
34
What are the other disease names for rhinovirus?
What is the epidemiology like?
‘Common cold’ - ‘rhino’ = nose
It has worldwide distribution and often occurs in epidemics in the autumn, winter and spring
35
What is the mode of transmission of rhinovirus?
Aerosolised respiratory secretions and droplets from the nose and eyes
e.g. Coughing and sneezing
36
What are the important clinical syndromes associated with rhinovirus?
**Common cold:**
* sneezing
* nasal obstruction and discharge
* sore throat
* cough
* headache and fever
37
What is the epidemiology of influenza virus like?
It infects BOTH humans and animals (**zoonosis**) and can spread between species
Swine flu comes from pigs and avian flu comes from birds
It peaks in winter annually
38
What is the virology of influenza like?
* There are 3 distinct types - A, B, C
* **influenza A mutates regularly** so the strains vary yearly
* 2 important surface proteins (**H & N**) have multiple variants
* this is used in nomenclature - H1N1 = swine flu
39
What is the mode of transmission of influenza virus?
Aerosolised respiratory secretions - coughs and sneezes
40
What are the 2 important clinical syndromes associated with influenza virus?
**Primary influenza illness:**
* fever, myalgia (muscle aches)
* **THEN** cough, sore throat, nasal discharge
**post-influenza secondary bacterial lung infection:**
* with *S. Pneumoniae, H, influenzae, S. Aureus*
41
What is the epidemiology of respiratory syncytial virus (RSV) like?
* Worldwide distribution
* occurs in epidemics in winter
* commonest in **young children**
* 70% are infected and 30% have had clinical illness in their first year of life
42
What is the mode of transmission of respiratory syncytial virus?
Aerosolisation of respiratory secretions
43
What is the important clinical syndrome associated with respiratory syncytial virus?
**Bronchiolitis:**
* this affects children **under 2 years**
* inflammation of the bronchioles causes cough, wheeze, hypoxia and apnoeas
* it does not affect adults as the bronchioles are wider
44
What is the epidemiology of HIV like?
HIV is **human immunodeficiency virus**
70% of people with HIV live in Sub-Saharan Africa
45
What is the mode of transmission of HIV like?
* Virus is present in blood, genital secretions and breast milk
* It is transmitted vertically, sexually or through needlestick
46
What is the clinical course of HIV like?
Which cells does the HIV virus target?
1. HIV targets **helper T lymphocytes (CD4)** cells of the cell-mediated immune system
2. 2-6 weeks after transmission, patients may develop **acute seroconversion illness** (flu-like)
3. **Asymptomatic chronic infection** follows
this is a steady state between HIV killing the CD4 cells and the CD4 cells regenerating, which lasts **5-15 years**
47
What happens in HIV after the period of asymptomatic chronic infection?
**AIDS**
This occurs when there is a **rise in viral load** and a **fall in CD4 count**
the patient becomes vulnerable to opportunistic infections
48
What are the 3 AIDS defining illnesses which may be fatal?
1. Pneumocystis pneumonia
2. Cryptococcal meningitis
3. Kaposi’s sarcoma
49
What is important to remember about using the term ‘hepatitis’?
hepatitis = inflammtion of the liver and death of hepatocytes
manyviruses can induce hepatitis as part of a wider clinical syndrome
there are **5** primarily heaptotropic viruses
50
What are the 5 primarily hepatotropic viruses?
How are they spread?
Hep A and E are spread via the faeco-oral route (e.g. contaminated water)
Hep B and C are blood borne
Hep D can only survive when Hep B is also present
51
What is the mode of transmission of Hep A and Hep E?
What clinical syndrome do they cause?
**Mode of transmission:**
* faeco-oral - virus is shed in faeces of an infected individual
**Clinical syndrome:**
* nausea, myalgia, fevers, jaundice, right upper quadrant pain
* usually self-limiting
* endemic in the developing world as it is associated with contaminated water
52
What is the epidemiology of Hep A and Hep E like?
**Hepatitis A:**
* prevalence of the antibody in adults varies from 10-50%
* this indicates previous exposure
**Hepatitis E:**
* clusters of cases are associated with pigs and undercooked pork
53
What are the symptomatic populations like in Hep A and Hep E infection?
**Hepatitis A:**
* infection in children is usually asymptomatic (esp. under 5)
* 50% of infected adults are symptomatic
**Hepatitis E:**
* 95% of cases are asymptomatic
* except pregnant women
54
What groups of people is Hepatitis A associated with?
1. Lower socio-economic groups
2. Returning tourists
3. Men who have sex with men (MSM)
55
What is a special consideration which must be taken into account for Hepatitis E?
**Fulminant hepatitis** with high mortality (25%) in infected pregnant women
56
What are the main modes of transmission of Hepatitis B?
The main mode of transmission is **vertically**
also sexually and parenteral (needle)
57
What is the clinical course of Hepatitis B like?
1. After transmission, **acute clinical hepatitis** may occur
90% of children and 50% of adults are asymptomatic
2. Hepatitis B is then cleared, or persists and becomes **chronic**
3. Over time chronic hepatitis progresses to **cirrhosis**, which progresses to **hepatocellular carcinoma**
58
What is the relationship between age and risk of chronicity in Hepatitis B infection?
Risk of chronicity is **inversely** related to age at infection
90% of those infected at birth will progress to chronic
only 5% of adult-acquired infections become chronic
59
What types of people tend to be infected with Hepatitis C?
The prevalence in developed countries is low
In the UK, 50% of **people who inject drugs (PWID)** have evidence of Hep C
60
What are the modes of transmission of Hepatitis C?
1. Sharing needles, needlestick injuries, transfusion of contaminated products
2. Vertical & sexual transmission is less common
61
What are the important clinical syndromes associated with hepatitis C infection?
* after transmission, 25% will develop **acute clinical hepatitis**
* 15% will clear the virus
* 85% will become **chronically infected**
* over time, chronic hepatitis leads to **cirrhosis**, which leads to **hepatocellular carcinoma**
62
What are the 2 main “diarrhoea & vomiting” viruses?
Norovirus (Norwalk) and Rotavirus
63
Where does rotavirus get its name from?
The virus looks like a wheel on electron microscopy
64
What is the epidemiology of Norwalk like?
* 90% of adults have been infected at some time
* immunity is short-lived (1 year), meaning you can get infected again
* it is associated with **point-source outbreaks**
* one single source in a confined area can affect a lot of people
* e.g. Cruise ships, hospitals
65
What is the mode of transmission and clinical syndrome of Norwalk?
**Mode of transmission:**
* ingestion/inhalation of aerosolised vomit particles
**clincal syndrome:**
* vomiting is a dominant feature
66
What is the epidemiology of Rotavirus like?
* It is a virus of **childhood**
* 80-100% are infected in first 3 years of life
* it is seasonal and peaks in winter
* it may cause infant mortality in the developing world
67
What is the mode of transmission and clinical syndrome associated with rotavirus?
**Mode of transmission:**
* faeco-oral
* through contaminated water and aerosolised faeces/vomit
**clinical syndrome:**
* fever, vomiting and watery diarrhoea
68
What is meant by ‘enteroviruses’?
This is a genus containing \> 70 serotypes
includes poliovirus, echoviruses and Coxsackie A and B
69
What is the epidemiology of enteroviruses like?
* Worldwide distribution
* peaks in summer and autumn in the UK
* 75% of cases occur in **under 15s**
* 90% are **asymptomatic** or have **mild febrile illness**
70
What is the mode of transmission and pathogenesis of enteroviruses?
* They take the **enteric route -** faeco-oral, through contaminated food/water
* they replicated in the gut but **_DO NOT_** cause GI symptoms
* they travel from the gut, to the lymph nodes and then into the blood
71
What are the 3 important clinical syndromes associated with enteroviruses?
1. Fever and rash syndromes in children including **hand foot and mouth**
2. **Meningitis** (50% of viral meningitis cases are enteroviruses)
3. **Severe disseminated disease** in neonates
72
What is the epidemiology and mode of transmission of mumps like?
**Epidemiology:**
* endemic childhood infection worldwide
* cases peak in temperate climates in winter
**Mode of transmission:**
* virus shed in saliva and respiratory secretions
* respiratory droplet transmission
73
What are the 3 important clinical syndromes associated with mumps?
**Acute parotitis:**
* unilateral or bilateral inflammation of the parotid gland
**Orchitis:**
* inflammation of testicles that affects 20-30% of infected males
* typically develops 4-5 days after parotitis
**Meningitis:**
* can lead to **meningoencephalitis** and **sensorineural deafness**
74
What is the epidemiology and mode of transmission of measles like?
**Epidemiology:**
* previously endemic in UK with 2-3 yearly endemics
* due to vaccine, it occurs in clusters of unvaccinated
**Mode of transmission:**
* respiratory droplet transmission
* the environment is still infectious after 2 hours
75
What are the 3 important clinical syndromes associated with measles?
**Primary measles:**
* fever, coryza, cough, conjunctivitis, **Koplik’s spots** on inside of cheek
* *_THEN_* maculopapular rash
**Acute post infectious measles encephalitis:**
* occurs 7-10 days after acute infection
* immune mediated with high mortality
* more common in under 1s
**Subacute sclerosing pan-encephalitis (SSPE):**
* occurs 7-10 years after natural measles infection
* progressive, degenerative and fatal disease of the CNS
76
What is meant by coryza?
catarrhal inflammation of the mucous membrane in the nose
”runny nose”
77
What are other names for rubella?
What is the epidemiology and mode of transmission?
Also known as “German measles”
**Epidemiology:**
* previously 6-8 yearly endemics in the UK
* it is now rare, due to vaccine
**Mode of transmission:**
* droplet transmission from respiratory route
78
What are the 2 important clinical syndromes associated with rubella?
**Primary rubella:**
* mild illness, fever and **maculopapular rash**
* arthralgia/arthritis occurs in 30% of adults (commonly in small joints of hand)
**Congenital rubella:**
* presents with a **classic triad:**
* **_bilateral cataracts, sensorineural deafness, microcephaly_**
* risk of foetal malformation is highest if mother is infected in first 12 weeks of pregnancy
79
What are the alternative names for Parvovirus B19?
What is the epidemiology and mode of transmission like?
‘Slapped cheek syndrome’ or ‘fifth disease’
**epidemiology:**
* peaks in spring
* 50% infected by 15 yrs, 90% by 90 yrs
**mode of transmission:**
* respiratory droplet transmission
* infects and kills **erythrocyte progenitor cells** - leading to **transient anaemia**
80
What are 3 important clinical syndromes associated with Parvovirus B19?
**Erythema infectiosum:**
* fever, coryza, **fiery red rash to cheeks,** ‘lacy’ rash to body
**Transient aplastic crisis:**
* affects those with a high erythrocyte turnover e.g. thalassaemia, sickle cell
* they suffer from severe anaemia and need a transfusion
**Infection in pregnancy:**
* 7-10% fetal loss if infected within first 20 weeks
* 2-3% develop **hydrops fetalis**
* this is severe fetal anaemia
81
What is the mechanism behind hydrops fetalis?
Insufficient oxygen in the blood causes the heart rate to increase to try and meet the demands of the tissues
this leads to heart failure
there is consequent oedema and ascites
82
What is meant by a ‘prion’?
Small infectious particle containing protein, but **_NO nucleic acid_**
83
What are the stages that cause a prion protein to cause problems?
1. Gene mutation leads to changes in folding pattern of protein
2. Prion becomes resistant to protease enzyme
3. Prion accumulates abnormally in cell
4. This promotes other proteins to fold abnormally
84
How can someone acquire an abnormal prion?
They are either:
1. **Inherited** genetic defects (can be a sporadic genetic change)
2. **Transmitted** via consumption or direct exposure
85
What are the 4 properties shared by all human prion diseases?
1. Manifest in the CNS
2. Produce **spongiform** change in brain tissue
3. Have **long incubation times** (30 yrs before symptoms start)
4. Are progressive and **fatal**
86
What is meant by sporadic Cruetzfeld-Jakob disease (CJD)?
What does it cause?
It is very rare and caused by a sporadic gene mutation
it is a neurological disease that causes progressive ataxia, depression, dementia and then death
87
What is meant by ‘ataxia’?
a group of disorders that affect co-ordination, balance and speech
88
What is the difference between sporadic CJD and ‘new variant CJD (nvCJD)’?
NvCJD is directly linked to **bovine spongiform encephalopathy (BSE)**
it is caused by the same structure prion as CJD
nvCJD cases are associated with consumption of infected beef
