Expert: Florence M Rollwagen - 4/15/2009

Question
If a virus can reproduce effectively in a culture of cells that produce interferon, what methods can be used to circumvent the interferon response?  How would this be done? Would the methods be used by the virus?

If this is out of your scope, please advise me to an individual that may provide further clarification.
Thank you!  

Answer
Hi Jasmine:  Thanks for your question:

When a virus infects a cell, the cell undergoes activation and protein synthesis, making interferon which will inhibit the progeny virus from infecting neighboring cells.

Interferon resistance can be a property of the eukaryotic cell or of the virus.  In some cases it has been shown that hepatitis C virus  envelope protein E2 inhibits the activity of the interferon-inducible protein kinase PKR in cell systems. PKR is an antiviral protein that blocks protein synthesis (and thereby interferon synthesis)  [https://www.sciencemag.org/cgi/content/full/287/5458/1555a]

The E2 mutation mimics the binding site of interferon, and essentially binds all the free interferon.  It blocks the signal that blocks the ability to inhibit protein synthesis, thereby nullifying the IFN message.

http://www.hhmi.org/news/lai.html

In other cases, viral mutations allow for resistance to interferon by blocking cellular activation genes in the cell.
[http://www.liebertonline.com/doi/abs/10.1089/1079990041689610]


Hope this helps, please write back if you have more questions.

FM Rollwagen, PhD