infectivity of naked viral DNA (vis-a-vis HBV)

[Karl Fischer]

In article <3pgfgr$lec at nntp3.u.washington.edu>, aurelia at u.washington.edu
(A. M. Lotto) wrote:

> I would assume then that caulimo 
> viruses like HBV form integrates with the host genome on occasion.

You are being very "kind", Amy - integration tends to be an extremely rare
event in duck hepatitis B virus infection, though increasing in frequency
with human and mammalian hepadnavirus infections. Chronic infection (as
opposed to acute) seems to be the hallmark associated with detectable
hepadnavirus integration events.

> A couple of questions have occured to me.  First of all, is the mechanism 
> for the formation of this integrate known yet? 

Some of the integrants studied in human HBV indicate that topoisomerase I
may be  associated with opening of the HBV covalently-closed circular form
prior to integration (JVirology 63(6) p. 2638-2643, 1989) and that the
integration may occur by illegitimate recombination through a weakly
homologous region (JVIrology 64 p.822-828, 1990).
 
> integration into the host human genes is hepatocellular cancer(or so it 
> is believed by the authors of this book, possibly in conjunction with a 
> carcinogenic co-factor),

In WHV-associated HCC, there is some very good evidence that integration
of the viral DNA is associated with up-regulation of N-myc and/or c-myc
(check the names of Pierre Tiollais and Christian Trepo for papers).
 
> HBV persist long and hard in humans, so is this integration a form of 
> latentcy?  Can the virus be 'cured' later from the genome?   

Strand breakage and integration renders the integrant incapable of
producing the  greater-than-genomic length pregenomic RNA (terminally
redundant) which is packaged and reverse transcribed to yield the DNA in
infectious virions; also, integrated hepatitis DNA is often rearranged
and/or deleted.
 
> If caulimovirus DNA is infectious on its own, does this also hold true 
> for HBV?  

Yes. Check out papers by Don Ganem, Bill Mason, Jesse Summers, to name but
three.

Hope this stuff was useful.

Cheers

Karl

-- 
Karl Fischer
kfischer at gpu.srv.ualberta.ca
tyr-2 at bones.biochem.ualberta.ca