Lecture 13 - Pathogenesis of Viral Infections II Flashcards
(50 cards)
Determinants of viral tropism 1) 2) 3) 4)
1) Availability of receptor
2) Local factors
3) Viral factors affecting accessibility to target tissue
4) Genome transcription requirements
Permissivity
Whether target cell has all of the right intracellular gene products for a virus to replicate in it
Why, if many viruses attach to receptors that are ubiquitous, can’t all viruses lead to systemic infections?
Permissivity of target cell, accessibility of target cell to virus, presence of local factors to allow viral infection
Rhinovirus receptor
ICAM-1
Why can’t rhinovirus lead to a systemic infection, even though it’s receptor is ICAM-1?
Replicates best at 33C. Can’t infect lower in the respiratory tract, as it is too hot
Why is it easier to catch rhinoviorus on a plane?
ICAM-1 is upregulated at higher altitudes
HSV receptor
Glycosaminoglycan
HSV tissue tropism
Epithelial cells, neurons
Local factors determining virus tropism
1)
2)
3)
1) Temperature (EG: rhinovirus)
2) Viral stability in extremes of pH (low in stomach, high in intestine)
3) Ability of virus to survive destruction of lipids by bile, proteins by pancreatic proteases
Example of viruses from the same family having different tissue tropisms
Both poliovirus and rhinovirus are picornaviruses.
Poliovirus is activated at low pH (stomach).
Rhinovirus is destroyed at low pH
Factors affecting ability of virus to access different tissues
1)
2)
1) Ability to replicate in macrophages (EG: dengue)
2) Ability to be released from basolateral surface of host cell (EG: vesicular stomatitis virus)
Virus that requires a cleavage-activating protease for infectiousness
Influenza.
Influenza HA is made as a single polypeptide chain. Must be cleaved by tryptase clara next to fusion peptide in order to be infectious.
This allows a conformational change at pH=5 in the endosome, which allows for membrane fusion.
How can H5N1 influenza infect tissues outside the respiratory tract?
Multiple basic amino acids inserted at tryptase clara cleavage site.
This allows cleavage by furins (ubiquitously-expressed in Golgi)
Example of a virus that uses cascade of host transcription factors to mediate protein expression
HPV
How does HPV regulate protein expression? 1) 2) 3) 4)
1) Codon usage. Different cells use different tRNAs for different amino acids.
2) HPV begins genome replication in the basal layer of the skin.
3) tRNAs required for late-stage genes aren’t available in basal cells.
4) Capsid proteins can only be made once germinal cells have migrated outwards and differentiated -> become permissive
Viruses that can result in oncogenesis
1)
2)
3)
1) Polyomaviruses
2) Adenoviruses
3) Oncogenic retroviruses
Viruses that lead to lytic infections
1)
2)
1) Enteroviruses
2) Reoviruses
Viruses that lead to chronic infection 1) 2) 3) 4)
1) HBV
2) HCV
3) HPV
4) Most retroviruses
What is a chronic infection vs a latent infection?
Chronic infection is the slow release of virus without killing the host cell
Latent infection is where there is no damage to host cell until a particular stimulus, where lytic infection begins
Types of persistent infections
Chronic infections
Latent infections
Viruses that can cause latent infections
1)
2)
3)
1) HSV
2) Varicella zoster
3) EBV
Mechanisms of viral disease progression
1)
2)
1) Viral-induced damage
2) Immunopathology
Cytocidal virus
Virus that results in cell death.
EG: Rotavirus killing enterocytes
Poliovirus killing spinal neurons
Why does influenza lead to a dry, hacking cough?
Ciliated epithelium is killed, leading to loss of mucus production
