Re infectivity of naked viral DNA

[Ian A. York]

In article <Pine.SOL.3.91.950522173713.15600B-100000-100000 at corona> Patrick O'Neil <patrick at corona> writes:
>> The naked DNA injections, in particular, are really surprising; but they 
>> do work.  
>
>If they do work, as stated, then it is not just suprizing to me but 
>rather disturbing since it indicates a very weak integrity to our 
>genomes...any ole DNA can get in and turn stable species into chaotic 
>mishmash at the very least.

Yeeeeessss. . .  . it really isn't that bad, I don't think.  The papers I 
looked at most carefully (I haven't followed the field closely for a 
while) suggested that the DNA didn't integrate but rather was maintained 
as an episome.  This was in muscle cells, and they were non-replicating, 
and the thought (well, my thought; I can't recall now whether this was 
specifically stated anywhere) was that there was some feature of the 
muscle cells that was friendlier to the DNA.  Another point is that one 
would expect the expression of foreign protein to lead to the destruction 
of the cells, by CTL (let's not talk about priming and so on for now).  
Myocytes are low MHC I expressors, so they might not be good CTL 
stimuklatos in the absence of inflammation leading to cytokines.  
Moreover, Ulmer pointed out to me that myocytes are very large 
multinucleated cells, and wondered whether they might not be highly 
resistant to CTL - being able to tolerate a certain number of hits.  

As I say I haven't looked closely at the latest literature.  I don't 
think the number of cell types shown to express the DNA has expanded that 
much; myocardia and endothelia, I think, and perhaps some of the lung 
tissues.  A case might be made that the cell type is critical.

By the way, Patrick, I sent those references to you by mail as well, but 
they bounced.  Perhaps you should have a word with your newsreader, if 
that's what puts a truncated address on your posts.

Ian
-- 
Ian York   (york at mbcrr.harvard.edu)
Dana-Farber Cancer Institute, 44 Binney St., Boston MA 02115
Phone (617)-632-3921     Fax  (617)-632-2627