Viral Pathogenesis Flashcards
What is pathogenicity?
The ability an organism has to cause disease
What 2 factors is pathogenicity composed of?
Infectivicity (ability to infect and colonise a host)–>Number of microbes necessary to initiate infection and cause disease.
Virulence (ability to cause host cell damage)–> occur along a spectrum, pathogenic organisms always cause disease while less virulent forms may not cause disease at all
In short terms give the steps of a virus life cycle. (7)
- Attachment
- Virus entry
- Cell membrane fusion
- Uncoating
- Replication
- Virus assembly
7.Virus release
What happens in virus attachment stage?
Highly specific process
Involves complimentary receptor on the surface of a susceptible host cells
Receptor can be protein or carbohydrate
initial binding is reversible
May cause a conformational change that then allows binding to a co-receptor
What has to happen in the virus entry stage and what are the 2 possible ways the virus can enter the host?
Viruses must cross the plasma membrane to enter the host cell
Can either enter by either:
1. Cell memrane fusion (non-endocytic pathways)
2. Receptor-mediated endocytes (Endocytotic pathways)
What happens in the cell membrane fusion stage?
Virus membrane fuses with plasma membrane and nucleocapsid is released into the cytoplasm
Explain the steps of the entry of Herpes simplex Virus
- Initial binding gB or gC to heparin sulphate (complex carbohydrate expressed on the surface of many cell types)
- Attachemnt of gD to,
- HveA (lymphocytes, fibroblasts, epithelial cells)
- Nectin 1 & 2 (neurons, epitheilial cells, fibroblast) - Fusion of the viral envelope with cell membrane.
Uses multiple types of spike glycoproteins to bind and enter different types of cells
Explain the steps of the entry of HIV
- Binding of HIV gp120 to CD4+ T-cells, induces conformational change in pg120.
- Enables binding of gp120 to CCRS or CXCR4, causes the gp120 trimer to break apart, allows gp41 to be pulled towards the cell membrane
- Fusion of gp41 with cell membrane, releases nucleocapsid into the cytoplasm
- Nucleocapsids are targeted to nucleus
Explain in 3 steps what receptor mediated endocytosis
- Virus particle binds to host cell receptor
- enters cell in an endosome
- Virus membrane fuses with membrane of the endosomeand nucleocapsid is released into cytoplasm
Explain the steps of the entry of the influenza virus (6 points)
- Binding of haemagglutinin (HA) to sialic acid receptor
- Internalisation in clathrin coated pit
- Movement into endocytotic vacuole which fuse with lysosome
- Low pH triggers conformational change in HA trimer
- Exposes fusion domain which allows fusion of iral membranes and endosome membrane
- Release of nucleocapsids into cytoplasm
What happens in the uncoating stage?
Release of viral nucleic acid from viral capsid
Process is variable: for some viruses
- Nucleic acids may still be in nucleoproteins complex
- The capsid is only partially disintegrated
What happens in the replication stage?
DNA viruses:
- dsDNA viruses use host machinery in the nucleus to make more dsDNA
- ssDNA converted to dsDNA then replicated like ds DNA
How do RNA viruses replicate?
Replicate in the cytoplasm (except influenza and retroviruses)
All make viral mRNA which the migrates into thecytoplasm to synthesis viral proteins using the host ribosomes
What happens in the Virus assembly stage?
Translation of viral proteins in the cytoplasm
Assembly by virus capsids from newly synthesised components (de novo assembly)
Encapsidation of the viral nucleic acid
What happens in the virus release?
Enveloped viruses by budding from the plasma membrane
acquire the envelope on the way out from plasma mebrane or internal membranes
Non-enveloped viruses released by cell lysis
