Lysogenic viruses and Gene Therapy

Peter pk20 at cornell.edu
Sun Dec 17 01:34:19 EST 1995


To the world's experts on virology,
	Here's a question that's been plaguing my mind for a while.  What 
causes HIV and other viruses to remain lysogenic/dormant for long periods of 
time, if they indeed do so?  Apparently HIV isn't detectable for six months 
after infection; is this due to dormancy? 
	Lambda phage stay put as long as there are high enough concentrations 
of lambda repressor protein around to keep its lytic genes inactive.  Do 
lysogenic animal viruses function similarly?  If so,  would it be possible to 
vaccinate against strains of viruses (maybe even HIV) by flooding a person's 
body with vectors carrying the repressor gene (gene therapy dream) so that no 
infecting virus will be able to replicate within the protected cells?  
	This would mean getting the repressor gene into enough of the 
patient's cells so that the density of unprotected cells is less than the 
critical mass needed for the virus to maintain infection.  An alternative 
would be to vaccinate early embryos (rediculous) or target ovaries and 
undeveloped oocytes. It would be necessary to prevent the random insertion of 
the viral repressor gene into an oncogene or some other critical sequence.  
	In the case of HIV, a more treatment oriented approach would be to 
target bone marrow cells that make lymphocytes.  Once we determine how to 
isolate those cells, maybe surgeons could remove some of an HIV patient's bone 
marrow, transform the T-lymphocute precursor cells with the viral repressor 
gene, and put the recombinant cells back into the patient.  These cells could 
then produce (hopefully) enough healthy T-cells to fight the infection, at 
least until the HIV mutates to the point when the repressor no longer 
recognizes and inhibits the viral replication genes.  
	A more focused question for retrovirus buffs is this; what keeps the 
fusion proteins that are packaged into the virus particles prior to budding in 
their inactive state?  Once the virus has budded off, these fusion proteins 
cut themselves up producing integrase, protease, reverse transcriptase, etc.  
What happens between the packaging and budding that inhibits protease 
activity? 
 
	Sorry for the rambling length,  but at least this letter is different 
from the ten before it.  If all of the above questions and ideas aren't 
immediately shot down for some basic reason, maybe we can solve the world's 
health problems in one swoop. maybe maybe maybe
	Thank you for humouring a curious student.  In my next letter, I'll 
pose naive questions about why we can't find some simple way of solving world 
peace, the welfare issue, and our overpopulation dilemma.  

-Peter

p.s.  I'm getting mixed signals from professors concerning gene therapy.  Some 
 seem to imply that it has great potential as a clinical tool while others 
cast it aside as something that is stirring up a lot of dreams but will soon 
fizzle out.  Should I be thinking about gearing my graduate studies towards 
gene therapy or is this foolish?  Which grad schools have good active research 
in this area?  I never run out of questions...



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