4.10 Viral Pathegenosis Flashcards
What must viruses do in order to be maintained in nature?
- Shed into the environment
- Taken up by an arthropod vector or needle
- passed congenitally
What are the routes of entry of a virus?
How do viruses enter through the respiratory tract?
- most important (and most frequent) site of entry
- many protective mechanisms
- mucus, cilia, alveolar macrophages
- viruses attach to specific receptors on epithelial cells • can remain localised or spread further
How do viruses enter via the alimentary tract?
- Ingested viruses can either be swallowed or infect the oropharynx and then be carried elsewhere but the oesophagus is rarely infected
- intestinal tract has mucus which prevents attachment to host cells but constant movement of contents allows some virus to contact specific receptors
What sort of viruses infect the alimentary tract?
Viruses that infect the intestinal tract are normally acid and bile resistant and (generally) do not have an envelope
Once in the alimentary tract what disease do viruses cause?
- Some viruses cause diarrhoea, others do not cause disease in the intestinal tract but spread from there to cause generalised infection
- HIV can infect via the rectal route
Which two viruses can enter via the alimentary tract?
- Herpes simplex virus 1 cold sores: acquired by direct contact of infected saliva with damaged skin of mouth
- Epstein Barr virus: infectious mononucleosis, aquired by direct contact of infected saliva with oropharynx
- Babies sucking contaminated objects or adolescents kissing
What viruses enter through the skin?
What other ways can viruses enter the body?
What are the mechanisms of viral spread throughout the body?
- Local spread on epithelial surfaces
- Sub-epithelial invasion and lymphatic spread
- HIV infect the rectal tract and gain access to T lymphocytes in underlying tissue and proliferate
- Sub-epithelial invasion and neuronal spread
- Rabies, infected animal bite through skin and pass virus to nerves and brain
- Spread via bloodstream - viraemia
What is the difference between systemic and disseminated infection?
- Disseminated infection is spread beyond primary site
- Systemic infection is many organs infected
How can viruses stay free in plasma?
- primary and secondary phases
- produced by infected vascular endothelium or released in large amounts from eg, liver and spleen
- neutralised by developing Ab response and removed by macrophages (duration usually 1-2wks)
What are cell associated viruses?
- Cell-associated viruses (leukocytes, platelets, erythrocytes)
- eg. measles spread by monocytes
- can persist from months to years if viral genome becomes latent to avoid CTL attack
How does viraemia occur?
Explain this
- direct injection of virus into the blood through mosquito or needle passive
- Virus attached to epitheliul cells, remove from bloodstream need to get into host cells = primary viraemia
- Go to secondary lymph tissues, secondary viraemia until cleared from the host
Why do we feel sick when having a virus?
- Viral damage to tissues and organs
- Consequences of the immune response
How does viral damage to tissues and organs occur?
- Cytocidal virus: disease may result directly from the cell death caused by viral replication
- tissue specific cell killing in rotavirus diarrhoea (enterocytes), and influenza virus infection (epithelial cells in respiratory tract).
How does sars-cov-2 cause viral damage to tissues and organs?
- It is a non-cytocidal virus where cells may lose their ability to perform particular functions
- Angiotensinogen is secreted by the liver and gets converted to Ang I by renin, which is mainly produced in the kidneys.
- Ang I gets cleaved by ACE to result in Ang II.
- Ang II is a ligand for the AT1 receptor and promotes vasoconstriction and hypertension.
- Alternatively, Ang II can bind to the AT2 receptor to inhibit vasoconstriction.
- ACE2 processes Ang II to Ang 1–7 which binds to the Mas receptor to induce vasodilation.
How can consequences of the immune response cause sickness?
What does the mass release of cytokines cause?
- “Cytokine storm” increases:
- IL-6 and others
- Immune activation
- Vascular permeability
- Inflammatory Monocytes & neutrophils
- Liver / kidney damage
- Hypoxia (< 80% saturation)
- Mechanical ventilation
- Death
How can the susceptibility of the host impact the progression of the disease?
- Genetic factors such as polymorphism in a receptor gene (CCR5 and HIV)
- Age: newborns and aged are more susceptible to severe disease (immature and waning response) but young suffer less from immunopathy
- Malnutrition decreases resistance such as vitamin A and measles
- Hormones and pregnancy where males and pregnant women are more susceptible
- Dual infections may result in more severe disease such as Hep B and D co-infection
What are the outcomes of a virus infection?
- Fatal: viral diseases where man is not the natural host have very high mortality rates eg. Ebola
- Full recovery: virus completely cleared by host’s immune system eg influenza
- Recovery but permanent damage: virus cleared but left with symptoms eg. poliomyelitis, cancer
- Persistent infection: virus not cleared and can resurface to cause disease
Why can we get some diseases over and over again?
- ineffective immunity eg. warts
- effective immunity but multiple serotypes of virus eg. rhinovirus
- constantly evolving virus
- over time within the population eg. influenza
- over time within a single patient eg. HIV
What are viral genomes continually changing as a result of?
- mutation (errors in copying the nucleic acid esp. RNA viruses)
- If two closely related viruses infect the same cell then:
- recombination (exchange of nucleic acid sequence)
- reassortment (swapping of segments for viruses that have segmented genomes)
What is the result of antigenic drift?
Antigenic drift resulting from RNA copying errors and selection of influenza virus with mutations in HA under the pressure of neutralising antibody giving rise to new seasonal epidemic strains
What is an example of a latent infection?
- eg. Varicella-zoster virus (Herpesviridae) (chickenpox and shingles)
- Latent in the spinal chord
How is HIV a latent disease?
- eg. Human Immunodeficiency virus (Retroviridae)
- AIDs
- HIV integrates in T cells in genome and latent infection slowly kill T cells
