Lecture 11 - Herpes 1 Flashcards
List 5 morphological features of Herpes viruses
- Large viruses
- linear dsDNA
- icosahedral nucleocapsid
- tegument proteins
- enveloped
What is the role of the nucleocapsid portal vertex in Herpesviruses?
It is a hole for inserting DNA into the nucleocapsid during assembly. It closes after vDNA has been inserted into the nucleocapsid
What cell type do all herpesviruses initially infect?
Epithelial cells
What type of host cell surface receptors do herpesviruses bind to? What is the feature of the receptor that allows for binding to occur?
Glycosaminoglycans: they are sulfated sugars with a negative charge that allows the virus to bind to them
What are the 2 types of attachment Herpesviruses undergo in order?
- initial attachment: reversible electrostatic interactions followed by
- stable attachment: irreversible binding to receptor
What 2 ways can a Herpesvirus penetrate a cell?
-Membrane-envelope fusion
OR
-Receptor-mediated endocytosis
What are 2 reasons for studying virus receptors
- Determining virus tropism
- Finding ways to interfere with virus attachment to host cells
Describe the steps in the Genetic Approach to finding a virus receptor
1) Start with a non-permissive cell type (one that the virus can’t infect and therefore doesn’t have a receptor for it)
2) Transfect non-permissive cells with genomic or cloned DNA from permissive cells. Some of the non-permissive cells will successfully transfect the DNA and express the receptor
3) Add recombinant virus virus carrying a drug-resistance gene to the transfected cells and select for with an antibiotic/cytotoxic drug. Only cells that were succesfully transfected would survive because they would express a receptor for the virus, absorb it and express drug resistance acquired from the virus.
Describe 3 ways you can check to see if cells transfected to express suspected virus receptors did in fact express the receptor, absorb virus and express vDNA?
1) add recombinant virus carrying drug resistance gene to cell culture - select for infected cells with antibiotics
2) add recombinant virus carrying an indicator gene to cell culture - only cells infected with virus will express indicator gene (ie. green fluorescence protein)
3) add fluorescently-labelled anti-receptor antibody - infected cells will fluoresce
What facilitates herpes mebrane fusion to host plasma membrane? What is the mechanism?
Viral fusion proteins. Receptor binding induces conformational changes in viral fusion proteins, pulling viral and host membranes together to induce fusion, pore formation and release of nucleocapsid into cytoplasm
How do herpesviruses get from the plasma membrane to the nucleus? Why must they use this method?
Via microtubules. Herpesviruses are to large to diffuse to nucleus and must use microtubules for transport.
What is the bulk flow direction along microtubules?
Retrograde: toward the nucleus
What happens to herpes tegument proteins upon virus entry?
They are released into the cytoplasm
What are the 2 main roles of tegument protieins
- nucleocapsid trafficking
- undermining host defenses
Name 2 herpes tegument proteins and their functions
ICP0: E3 ubiquitin ligase that targets antiviral protein PML for the proteosome
VHS (virion host shutoff): enzyme that cuts host mRNA to prevent antiviral responses