35.5 Cellular and Systemic Consequences of Infection Flashcards
Are all viruses pathogenic?
No
What does the outcome of an infection rely on?
A wide range of host and viral factors
*e.g. age/ health/ state of immune system/ dose of virus (likely due to extent of spread/ cell death)
Why do viral infections cause disease in the organism as a whole?
Symptoms are generally due to the limitations of viral tropism.
*to infect a cell lineage, viruses must be able to enter host cells w/out evoking a strong immune response so they target specific surface proteins.
Therefore, systemic consequences of infection generally linked to the cell lineages that are affected.
What does infection usually result in?
The death of cells
What are cytopathic effects and what are they caused by?
Morphological changes within the host cells as side effects of the viral life cycle.
What are the cytopathic effects of polio on motor neurons?
- Inhibition of cell protein synthesis (by cleavage of eukaryotic translation initiation factor eIF4G by viral protein 2A).
- Inhibition of cell transcription by all three classes of RNA polymerases.
- Cytoskeletal changes, cell rounding and detachment from substratum.
- Cell lysis.
Lots of the pathogenesis of polio also results from apoptosis of cells.
What are the cytopathic effects of HIV on CD4+ T-cells?
HIV-1 is also known to have a direct, cytopathic effect on CD4+ T-cells, leading to membrane ballooning and rupture for the lytic death thought to be a primary cause of T-cell depletion in the course of the disease
Which part of human immunity is important in hepatitis pathogenesis?
Cell-mediated immunity -> This is leads to bystander cell death and therefore damage to the liver, as well as inflammation.
Is cellular transformation by DNA viruses common?
No, it is a comparatively rare and atypical consequence of viral infection.
What can EBV cause?
*Infectious mononucleosis
aka glandular fever.
How does EBV cause glandular fever?
fever, a sore throat, enlargement of the lymph nodes of the neck and fatigue due to replication within the pharyngeal epithelium acutely (fever, sore throat) before moving on to infect B-cells via CD21 and leading to swelling of the lymph nodes as CTLs begin to target these infected lymphocytes
How can EBV lead to cancer development?
production of the viral protein EBNA-1, which is used in opposition to antigen presentation and improving replication of the virus in a host, is known to increase DNA replication and BART/EBER/LMP gene expression (which causes the likelihood of apoptosis to decrease), thus increasing the likelihood of somatic mutation and development of cancers from infected cells
What is EBV a predisposing factor for?
*Burkitt’s Lymphoma
*Nasopharyngeal carcinoma
There is a requirement for other factors.
What does Papilloma virus cause?
common warts (benign tumours)
What is Papilloma virus a predisposing factor for?
*carcinoma of the uterine cervix + other carcinomas by certain serotypes.
- e.g. ano-genital carcinomas/ head and neck squamous cell carcinomas.
*by 6 strains
How does Papilloma virus predispose to carcinomas?
Proteins E6 and E7 are linked to the development of cancer. They up-regulate the cell cycle.
*E6 interferes w/ normal p53 signalling that suppresses cellular survival signals.
*E7 activates E2F transcription factors that help u[regulate genes necessary for mitosis. Also RB1 inhibition so cell can immediately progress from G1 to S phase.
What can cause Hepatocellular carcinoma?
Chronic Hepatitis B Virus and Hepatitis C Virus infection
*in cases of severe chronic infection.
How do DNA viruses with small genomes and some RNA viruses transform cells?
These acute viruses benefit from the rapid replication of host cells to increase their own numbers further without needing to account for the longer-term effects to the host, they can carry genetic material that can be integrated into the host cell to alter replication.
*e.g. RSV injects a proto-oncogene which is transcribed to promote host cell replication + directly and rapidly induces tumour development.
What is cellular latency?
The persistence of viral genomes in cells without overt expression of new viruses.
Give examples of viruses that display cellular latency
Herpes virus and retroviruses
What is clinical latency?
The temporary absence of symptoms in spite of infection, resulting from cellular latency, active immunity etc.
Describe how latency of HIV works.
- HIV-1 can infect macrophages and T-cells (which can become memory T cells)
- When these cells are in long-term reservoirs, they are not active and therefore there is no transcription of the viral genome -> Thus, there is no immune response against the viral proteins and the virus is latent
- These viruses in these cells are resistant to drugs and the immune system
What are some potential approaches to curing HIV?
The problem with HIV is that a latent infection is very difficult to treat. The approaches include:
- ‘Berlin’ and ‘London’ patients, who received bone marrow transplants from individuals with no CCR5 receptors on their cells -> This resulted in there being no detectable virus for many years, making these patients essentially cured. However, this is not widely viable for every HIV patient.
- ‘Kick and kill’ approach, where latency is reversed by activating transcription in infected memory T-cells (so that they can be killed by cytotoxic T-cells) and then re-infection of new cells is prevented using strong anti-retroviral drugs
How can dissemination be classified?
Local or systemic
