Lecture 5- Patterns of viral infection Flashcards
Define ‘tropism’
The predisposition of viruses to infect certain tissues and not others
What are arboviruses?
Viruses spread by insects
Which three factors does tropism depend on?
1) Susceptibility- receptor interactions
2) Permissivity- ability to use host cell to complete replication
3) Accessibility- whether the virus can reach a tissue
Which factor affects the tropism of HIV? explain…
Susceptibility:
- HIV usually binds to CD4 and CCR5/CXCR4 receptors
- Delta 32 mutation in CCR5= resistance to HIV
- Some produces lots of chemokine which blocks co-receptor
Which receptor do measles have and which host cell receptors do they bind to? * Which receptor does the vaccine strain of measles bind to?
Measles- Haemagglutinin Host cell: - CD155 (SLAM) - Nectin 4 Vaccine strain of measles uses CD55
How does measles infect a person?
- enters through respiratory tract
- Binds to SLAM on dendritic cells
- rides over to the lymph nodes
- binds to more immune cells using SLAM and causes immunosuppression
- Uses NECTIN 4 to leave the host at airway epithelial cells
How does influenza enter its host cell?
- Haemagglutinin receptors bind to sialic acid on surface of cells
- enters cell via endosome
What causes the influenza virus to change conformation intracellularly? Why does it change conformation?
- low pH in endosome causes conformational change
- Influenza can then fuse with endosomal membrane and uncoats
What affects influenza tropism?
- needs particular protease for membrane fusion and uncaring
- only fluid lining the lungs contain the right protease
Define pathogenicity
Ability of virus to cause disease
Define virulence
Capacity of virus to cause disease
What are iatrogenic and nosocomial sources of infection?
1) iatrogenic= as a result of medical treatment (contaminated needles)
2) nosocomial= hospital acquired
What is the name of the secondary viraemia caused by VZV? explain how the secondary viraemia is caused
Shingles
- VZV infects skin cells and PBMCs
- VZV infects the sensory neurones and remains latent here
- Shingles (herpes zoster) manifests in adulthood when immunity is impaired. Virus is reactivated in sensory neurone.
- Causes painful rash
What are the different patterns of viral infection?
Acute- followed by viral clearance
Persistent- latent, slow, transforming
Long incubations
Oncogenesis- affect cell proliferation
What are the different outcomes of an acute infection? Give examples of viruses for each
1) Clearance- with cold and influenza. Adaptive response provides immunity
2) Death- Smallpox (infection of skin) and dengue (leakage of plasma from capillaries)
3) Accidental pathogenesis- polio (paralysis) and rubella in foetus has a tropism for neuronal tissue (Deafness, eye abnormalities and congenital heart disease)
What are the two different types of persistent viral infections?
1) Chronic- low level of replication of viruses (papillomavirus in warts)
2) Latent- viral genome remains but symptoms seen at episodes of reactivation when immunity declines (herpes viruses- HSV, VZV)
How do viruses remain persistent?
- Evade immune surveillance by MHC down regulation (cytomegalovirus)
- Escape CTLs by mutating (Hep C)
- Infect tissues with reduced immune surveillance e.g. CNS (measles, herpes and papillomavirus-skin)
How do viruses cause oncogenesis? Give examples of ontogenetic viruses
- virus may encode oncogenes
- may interfere with cell cycle to enhance their replication
Examples: - papillomairus: encodes inhibitors of tumour suppressor p53, E6 and E7 –> forced into S phase
- HHV8 and Merkel cell polyoma
- HTLV-1 causes adult leukaemia
What do HBV and HCV cause?
Hepatocellular carcinoma
HBV- what sort of virus is it and how is it spread
- Hepadnavirus
- spread by blood and semen
What sort of virus is Epstein Barr Virus?
which cancers can it cause
- Gamma herpes virus
- Burkitts lymphoma
- Hodgkins lymph
- Nasopharyngeal carcinoma
How is Epstein Barr Virus spread?
In saliva
What does the outcome of a virus infection depend on?
- virus sequence
- virus load
- host immune response/ status
- host co-mobidity
- co-infections
- other medications
- host genetics
- host age and gender
Give an example of how viral sequence affects a viral infection
Polio
- Sabin, live attenuate vaccine
- Poliomyelitis, invades motor neurone and causes paralysis
Give an example of how viral load affects a viral infection
Chickenpox
- older sibling has Midler illness than younger. Second child is in closer contact and is infected by larger viral load
Give examples of co-infctions affecting a viral infection
- secondary bacterial infection after influenza
- HHV8 causes Kaposi’s Sarcoma in HIV patients
- Hepatitis Delta virus infects Hep B patients ( causes liver disease+ cirrhosis)
Give examples of how genetic resistance and susceptibility affects viral infections
- CCR5 delta 32 mutation= HIV protection
- KIRs- Hep C
Which comorbidities predispose patients to influenza
- Asthma
- obesity
- immunosuppression
- immunodeficiency
- elderly
- diabetes mellitus
- pregnancy
