Was Re:... Hepadnaviruses??Related to retroviruses?

[Sandra Russell]

In <kfischer-2705951419170001 at duckter.glaxo.med.ualberta.ca> 
kfischer at gpu.srv.ualberta.ca (Karl Fischer) writes: 

>
>In article <3q6v22$qra at ixnews4.ix.netcom.com>, srussell at ix.netcom.com
>(Sandra Russell) wrote:
>
>
>> Excuse a lay question: since hepadnaviruses sort of look like 
>> retroviruses, and have the same transmission patterns as HIV, and are 
>> carcinogenic, and since their DNA replicase even has reverse 
>> transcriptase activity, I wonder if they are related?  Is there any 
>> homology at all to these viruses and the retroviruses?
>
>When I first started working on hepadnaviruses, this was a fundamental
>question asked by myself and other grad students in the lab. There was 
a
>paper entitled "Close evolutionary relatedness of the hepatitis B virus
>and murine leukemia virus polymerase gene sequences" by Roger Miller
>(Virology 164 p147-155, 1988) which attempted to address this. Regions 
of
>the hepatitis B polymerase do indeed share homology with retroviral
>reverse transcriptases. As well, there is some homology between gag and
>hepatitis core protein (Miller and Robinson, PNAS 83, 2531-2535, 1986).
>
> 
>> Could retroviruses be hepadnaviruses that just got packaged wrong 
(along 
>> with some RT?)
> 
>Hmmm...good question, let us center on the differences. Hepadnaviruses 
use
>protein priming (similar to adenoviruses and bacteriophages phi29 and
>PRD1) to initiate first strand DNA synthesis while retroviruses use
>tRNAs.The hepadnavirus replication involves a nuclear unintegrated 
species
>(covalently-closed circular) ds DNA while retroviruses require 
integration
>of ds DNA into the host DNA. Roughly speaking, retros have a genetic
>complement which is >3X larger than hepadnaviruses, as well as more 
gene
>products/regulatory elements.
>
>To your original question, based on the above perhaps hepadnaviruses 
are
>streamlined decendants of retroviruses instead of the reverse? Thoughts
>anyone?
>
>Cheers
>
>Karl
>
>-- 
>Karl Fischer
>kfischer at gpu.srv.ualberta.ca
>tyr-2 at bones.biochem.ualberta.ca
>

Thanks, that was just the sort of comment I was hoping to get.  Okay, 
perhaps the other way then.  The similarity of the RTs suggests a 
natural explanation for the recent disaster using a nucleoside analogue 
on Hep B patients-- it nailed all their mitochondrial transcriptases, 
and wiped out their livers.  Mitochondrial toxicity has been the major 
problem with nucleoside analogue HIV drugs, too, but oddly enough in 
nerve and muscle, not liver.  Wonder why not?  The lentiviruses use an 
Mg dependent RT, but I know that type C retroviruses use an Mn dependent 
one.  If mitrochondria are descendents of bacteria, I wonder if their 
DNA replicase is Mn dependent, too, like their SOD is.  Anybody know?  
Anybody know the metal dependence of the hepadnavirus DNA replicase?

                                             Steve Harris, M.D.