Re: How can viral DNA enter the cell nucleus if human DNA can't leave it?

Hi Danny,

It is true that human DNA cannot easily get out of the cell nucleus. It cannot do so because it is very tightly packed in a large complex of DNA and proteins (mainly histones) called a chromosome. This superstructure is so big that when the cell divides, and using only a light microscope, we can see each chromosome in the cell. Another reason why DNA cannot leave the cell nucleus is that nuclear pores will only allow large molecules (such as DNA) inside or outside the nucleus if these large molecules are in a complex with proteins that target these molecules to the nuclear pore.

For viral DNA, in the case of lentiviruses (HIV) for example, the DNA is fairly small (compared with the cell DNA) and is "coated" with proteins (nucleoproteins) that keep the DNA safe from degradation inside the cell cytoplasm. These nucleoproteins or another virus-encoded protein (p17 or Vpr?), have the property to target DNA to the nuclear pore but also to "convince" the nuclear pore to let the viral DNA enter the cell nucleus.

Other viruses, like oncoviruses, are unable to get in the nucleus that easily. They have to wait for the cell to divide (which cause a breakdown of the nucleus membrane) in order to get in the nucleus of one (and only one) of the daughter cells (when the nucleus membrane forms again after DNA replication).

For other viruses ( polyomaviruses), they get into the cell by endocytosis (i.e. the cell "eats" them) and they then "force" the cell to shuttle the endocytic vesicle to the nucleus where they penetrate by direct fusion with the nuclear membrane (no need for nuclear pores in this case).

Evolution has given many weapons to viruses in order to ensure their survival even in a cell that has a nucleus with a fairly stable membrane.

It must be stated, however, that much is still unknown in this field and further research on this subject is bound to produce some very interesting answers to many mysteries of the biology of viruses.

So cellular DNA cannot leave the cell nucleus (except during cell division) because it is too big, and because it does not have the "evolutionary drive" to do so. Viral DNA is small and has a great deal of "evolutionary drive" to enter the cell nucleus - where all the replicative machinery lives and all the resources needed are available to take over the cell.

I hope this answers your question and don't hesitate to ask if something is on your mind... it's the best way to learn!

Ciao!

Mike

P.S.: Much of the information presented here came from Fundamental Virology, 3rd edition, edited by Bernard N. Fields, David M. Knipe and Peter M. Howley, Lippincott-Raven Publishers (1996) 1340pp, ISBN 0-7817-0284-4"