Viruses and immune system evasion Flashcards
What is herpes simplex virus type 1?
- HSV type 1
- cutaneous exposure, mouth cold sores
- herpesviridae family of viruses
- acute infection
- Viral load is not cleared
- Remains as latent infection in DORSAL ROOT GANGLIA innervating the mucosa of that acute infection
- Immunodeficiency may be caused through severe cases
What is herpes simplex virus type 2?
- genital herpes
- Viral load is not cleared
- Remains as latent infection in DORSAL ROOT GANGLIA innervating the mucosa of that acute infection
- Immunodeficiency may be caused through severe cases
How is HSV diagnosed?
HSV = herpes simplex virus
type 1 and 2
- Sx based
- swabs taken for genital infection, testing using PCR
What is Varicella Zoster infection?
= chickenpox
- belongs to herpesviridae virus family
- Dx usually based on Sx
- Can take swab at ulcer base and send for PCR
Virus remains as latent infection in dorsal root ganglia
Reactivations = shingles
once infected, virus never completely clears
What is cytomegalovirus?
- congenital CMV
- causes hearing, visual and intellectual impairment
- herpeviridae virus family
- more common in developing countries and lower socioeconomic groups
- often asymptomatic
- Sx: fever, lymphadenopathy, fatigue, muscle aches, appetite loss and stiff joints
What are the features of human CMV infection?
- once infected, virus is not cleared
- latent, remains in lymphocytes
- can be reactivated
- infection (reactivated or primary) during pregnancy can be transmitted to foetus
What is EBV?
= epstein barr virus
- herpesviridae virus family
- latency in lymphocytes
- transmitted by contact with body fluids e.g saliva or via sexual contact
Glandular fever Sx: 4-6 weeks to appear
Sx: fatigue, fever, pharyngitis, cervical lymphadenopathy, hepatosplenomegaly, rash
- Dx: Sx and IgM Ab test
What are the common herpesviridae viruses?
- HSV type 1
- HSV type 2
- Varicella Zoster
- CMV
- EBV
All stay latent then reactivate once infected
What is adenovirus?
- Eye infections: transmission via contact
- Respiratory infection
- Gastro infection: transmission via faecal-oral
What is pappillomavirus? How is it Dx?
non-enveloped DNA virus
Dx: usually based on Sx but can also do PCR
What is measles? How is it Dx?
measles virus: RNA virus, transmitted via respiratory tract
Dx: IgM Ab serology, throat swab looking for viral RNA by PCR
What is rubella? How is it Dx?
RNA virus
airborne transmission
Can also cause congenital infection if transmitted mother to baby
Dx: blood sample from baby to look for IgM
Carry out PCR for viral RNA
What is mumps? How is it Dx?
RNA virus
airborne transmission
Sx: swollen salivary glands, fever, headache, muscle ache, swollen tested
Dx: Sx, salivary PCR, serum IgM
What is parvovirus B19? How is it Dx?
DNA virus
respiratory transmission
can also be transmitted in utero to foetus
causes erthyema infectiosum (classic ‘slapped cheek’ appearance)
Dx: IgM, blood PCR for viral nucleic acid
What is rotavirus? How is it Dx?
dsRNA virus
faecal oral transmission
causes diarrhoea (particular in infants)
Dx: Sx, PCR, Ag detection test
What is haemorrhagic fever virus? How is it Dx?
viruses e.g. Lassa fever (arenaviridae)
RNA virus, enveloped
infected animals shed virus in urine/faeces
Direct contact with this infected material through inhalation or ingestion causes infection transmission
Dx: Blood PCR
What are the early Sx of Ebola infection?
Sx can appear between 2-21 days after exposure Is only contagious after Sx begin - fever - headache - diarrhoea - vomiting - stomach and muscle pain - unexplained bleeding or bruising Dx: blood PCR
What is Ebola virus?
RNA virus
enveloped
natural reservoir not yet known
possible that first patient was infected via contact with infected animal (bat or primate)
Then person to person transmission
Need direct contact with blood or bodily fluids
e.g. via contaminated needles
How does Ebola enter the host?
enter via mucus membranes and breaks in skin barrier or parenterally
infects many cell types
migrates from initial site to LNs then liver, spleen and adrenal glands
Causes tissue necrosis, inflammation and organ failure
What is rabies virus?
enveloped, RNA virus
transmitted via bites and entry of infected saliva into systemic circulation
Dx: PCR of CSF and nuchal skin biopsy
What is HIV?
human immunodeficiency virus
blood borne virus (BBV)
What are the key structural features of viruses?
small size, only visible with electron microscope
many viruses are ICOSAHEDRAL shaped (20 sides)
can be enveloped or not enveloped
RNA or DNA
How is Dx made for viral infections?
CLINICAL (big proportion)
Sx, duration, contact with infection sources, geographical location, lifestyle, risk factors
LAB RESULT Ab against virus (IgM or IgG depending on duration and specificity) using enzyme immunoassay IgM: recent infection IgG: past or chronic infection PCR: replicating nucleic acids (qRT-PCR)
Which viruses cause hepatitis?
HAV HBV HCV HDV HEV CMV EBV
What is hepatitis A virus?
27-28 nm icosahedral non-enveloped ssRNA (linear) vaccine available
15-45 days incubation period
acute onset
affects children and young adults more commonly
faecal oral transmission and low rate sexually
Dx: IgM serology
Mild infection
0.1% fulminant disease
does not become chronic
0.2% mortality
What is hepatitis B virus?
42nm nucleocapsid core enveloped (contains HepBsAg) can circulate as incomplete (surface Ag only to trick host immune system) ss/ds DNA (circular/plasmid)
20-150 days incubation period
insidious or acute onset
affects children or young adults (more common)
percutenous, perinatal or sexual transmission
Dx: IgM serology and PCR
Often asymptomatic
Can become chronic (especially when infected in early childhood)
0.5-2% cancer risk
How does HepB virus elevate cancer causing mechanisms?
HepB virus itself lacks oncogenes
Long latency between HBV and hepatocellular carcinoma development
viral DNA integrates into genome, which can itself disrupt host oncogenes
Also, chronic inflammation can increase turnover/regeneration via stimulation of proliferative genes
What is hepatitis C virus?
30-60nm
enveloped
ssRNA (linear)
positive sense RNA (can act as mRNA for viral protein synthesis)
15-150 days incubation period
insidious onset
affects all ages, more common in adults
percutaneous (+perinatal+sexual) transmission
Dx: IgG serology (no reliable IgM test) + Blood PCR
0.1% fulminant disease
75% develop chronic infection
cancer risk (of HCC)
0.2% mortality
What are the main risk factors for HCV infection?
highest: IVDU then: - sexual/STD history - prison - transfusions - Haemodialysis (long term)
What is hepatitis D virus?
35-37nm
hybrid particle (HDV core, HBsAg)
ssRNA (linear, -ve sense)
Can only be infected via co-infection with HepB
15-150 days incubation period insidious or acute onset any age affected percutaneous, perinatal and sexual transmission can be severe disease 5-20% fulminant disease chronic infection possible 2-20% mortality HBV vaccine (prophylaxis) Dx: HDV Ab monitor HDV RNA levels by PCR
What is hepatitis E virus?
32-34nm
non-enveloped
icosahedral
ssRNA (linear, +ve sense)
15-60 days incubation period acute onset affects young adults faecal oral transmission generally mild but can be severe in pregnancy 1-2% fulminant disease 0.2% mortality Dx: IgM serology
Which hepatitis viruses can cause persistent/chronic infection?
HBV
HCV
HDV (remember only with HBV)
Which hep viruses have vaccines available?
HAV
HBV
Which viruses can our immune system clear?
rhinovirus (common cold)
influenza
rotavirus, norovirus (diarrhoea)
adenovirus (sore throat)
How do some viruses evade host immune system?
change viral proteins (immune system will not recognise new proteins) e.g. influenza strains
different types of the same virus (e.g. rhinovirus and adenovirus)
infect at time when immune defence is compromised e.g. varicella in perinatal period
large dose of virus, immune system not equipped e.g. HSV in perinatal period
How does the CVM virus evade immune responses?
transplacental viral transmission
Foetus unable to mount an adequate immune response
primary infection will occur in mother (during pregnancy)
same can happen with rubella virus
How does HBV evade the immune system?
releases decoy particle (= HBsAg)
this diverts the immune response and the core virus (containing the virulence factors) are left alone
How does latency aid evasion of immune response?
aim to establish latency after initial acute infection
enter sites where the immune cells have restricted access e.g. dorsal root ganglia or lymphocytes
here, they only make very few viral proteins
e.g. herpesviridae family of viruses
How does CMV evade immune response?
CMV = cytomegalovirus down regulate MHC class I molecules, therefore impairs Ag presentation prevents detection by CD8+ CTLs
MHC class I - present on all nucleated host cells
What are the privileged sites for HIV and CMV?
= sites where they are most likely to establish latency infection
lymphocytes
macrophages
(low level replication will occur here)
What cancers do EBV infections increase risk of?
EBV = Epstein Barr virus
Burkitt’s lymphoma
Nasopharyngeal carcinoma
What does HPV increase risk of?
HP = human papilloma virus
cervical cancer
How do viral infections increase cancer risk?
viruses replicating within cells will integrate with host genome
elevated risk if this is in cells that do not normally divide that much
integration may target host oncogenes and tumour suppressor genes
promotes host cell proliferation
Which viruses have been successfully eradicated?
small pox - eradicated
poliovirus - almost
in progress: mumps, measles, rubella, papilloma, hepatitis
How is hepatitis B being controlled successfully in theUK?
Infants given 3-4 doses of HBV vaccine
HBsAg seropositive rates fallen to <1%
HepB Ig given to infants within 24 hr of birth if mother is at high risk of vertical transmission (if HBsAg or HBeAg positive)
How does the HBsAg aid the Hep B virus in the host?
HBsAg: surface Ag
thought to aid the entry of HBV into hepatocytes (via attachment to PM receptors)
