Lecture 4 Flashcards
Main differences between plant and animal viruses in how they enter cells?
Plant viruses harness mechanical force to enter cells due to the plant cell walls.
Animal viruses cell entry is active process: governed by receptor mediated entry. Plants is passive in this sense.
How do animal viruses initiate cell entry?
What are the substrates used in bacterial systems?
Initial attachment is non-specific binding, not the receptor that mediates entry. General membrane components.
Two most prominent are silica acid and herapin sulphate proteoglycan (HSPG).
Bacteriophages bind to LPS in G-ve and Teichoic acid in G+ve.
How does HIV mediated entry occur?
HIV initially binds to HSPG on surface, then to its receptor, CoR.
Its CoR is so close to membrane, requires another protein to assist, CD4.
This second attachment activates virus (contracting to form pore, and delivery of genetic material inside the cell).
How does bacteria enveloped phage Phi6 enter cells?
Unique way. Binds to bacteria Pili. The pilus retracts down to bacterial outer membrane. Virus then undergoes fusion, destroys cell wall and then penetrates the plasma membrane.
This mechanism more resembles animal virus than bacteriovirus.
Once attached, how do viruses get ready for entry?
After receptor recognition, conformational changes in virus that exposes a domain that initiates entry (e.g. by creating a pore in the cell) e.g. poliovirus.
Conformational changes can also be cleavage of a viral protein, exposing this domain (e.g. reovirus)
What are HIV’s two receptors and why does it have two receptors?
CCR5 and CXCR4. They are not expressed on the same cell so virus has multiple targets.
How does HIV enter cells once attachment is complete?
Trimolecular complex is key to trigger fusion events.
CD4 binding to gp120 (viral) exposing gp41 fusion peptide that binds to membrane, pulling in CCR5 or CXCR4 to bind gp120, membranes so close that fusion occurs.
How is entry governed by influenza (Orthomyxovirus)
- Virus binds to sialic acid.
- Induces conformational change that leads to fusion.
- Requires low pH.
- Fusion peptide is hidden.
- When HA1 is cleaved in low pH, exposes fusion peptide, causing fusion.
Summary:
Fusion is activated by pH decrease in endoscopes. Protonation pulls trimers apart, allowing water entry, modifying HAS2, activating for fusion
What is the tropism of a virus?
Which cells or tissues the virus targets. Viruses are specialised to enter cells at the point where they enter the body (e.g. lung cells if inhaled). Defines the tropism of the virus.
How has a genetic mutation in humans led to therapeutics against HIV?
Some humans with a CCR5 Delta 32 (recessive mutation deletion) meant they were completely resistant to HIV infection.
CCR5 was no longer expressed at cell surface, HIV cannot infect target cells.
Its allele frequency in Caucasians is ~10% but absent in other ethnic groups. Has recent origin (2000 years).
Developed a small molecule that binds to HIV binding proteins, that inhibit CCR5 binding (or CXCR4).
gp41 mimic.
Used as part of Highly Active Anti-Retroviral Therapy (HAART) drug treatment cocktail that repressed HIV.
