In article <51853 at sci.med.aids>, WARogers RJDuran <matilda1 at flash.net> wrote:
>Axel Boldt wrote in message <51685 at sci.med.aids>...
>>Hi,
>>>>I have two questions about HIV:
>>>>1) Is the HIV provirus always integrated at the same spot in the host
>> cell's genome? If yes, where?
>>Unfortunately, the answer to your question is a negative one. One of the
>primary reasons that the "Vaccination" approach to containing the virus is
>not working is because the virus has no particular spot on the RNA and DNA
>chain where it goes to. It is like a microscopic octopus that grabs hold at
>anyplace.
Actually, the biggest obstacles to immunization are the extreme antigenic
diversity of HIV strains, particularly in the env gene, the glycosylation
(sugar coating - hides the proteins from immune recognition) of surface
proteins, and the very open question of whether antibody response is
ever enough to stop the virus. There are some new approaches to prime
the other arm of the immune system, the cell mediated immunity, to try
and initiate a cytotoxic lymphocyte response (CTL). This approach is
supported by findings in long term survivors, who typically have a
very vigorous CTL response, and who secrete a still poorly characterized
protein from their CD8 cells that stops viral replication. Where the
provirus is integrated in host DNA is pretty irrelevant to questions
of immunization, although it is important is gene-therapy considerations.
>>>2) What exactly causes the provirus to become active and produce new
>> particles -- is it the activation of the T-cell by antigen?
>>Someone please correct me if I am wrong, but I do not believe that the virus
>actually creates new particles as such. To the best of my knowledge, the
>mature virus is composed of only a single strand of RNA.
No, it's actually double stranded RNA
It does not have
>any DNA, like the nucleus of the T-Cell does.
This is true for the portion of the viral life cycle where it is extracellular.
But one of the first things to occur after the virus enters a cell is
the transcription of viral RNA into viral DNA (reverse transcription).
The viral DNA is then drawn into the nucleus by poorly understood processes,
where the viral integrase incorporates the viral DNA into the host DNA.
The nucleus of the T-Cell has
>both RNA and DNA.
All DNA that is "active" produces mRNA and cRNA transcripts, which then code
for specific proteins. DNA in the absence of RNA is quiescent: it needs
to make RNA as a neccesary intermediate step in protein synthesis.
> To answer your question, when the virus enters the T-Cell
>with it's single strand of RNA, it does not create new particles to
>replicate itself, it simply uses the DNA genes that are already there,
>inside the T-Cell. That's how it puts itself together.
It's actually a little more complex then that. There is a very complex
interplay of viral and cellular enzymes and proteins that are required
for the production of new virions. For example: without the HIV-encoded
protease enzyme, viral proteins would never be cleaved to the right
length to create viable virions.
>>What happens next, if I may be so bold, is that the virus, now having put
>itself together with a bunch of new genes, has killed the T-Cell. The
>T-Cell no longer has all of it's genes, because the virus has taken them
>away
There is no evidence for that. The mechanisms of HIV-mediated cytotoxicity
are still somewhat opaque - there are probably multiple mechanisms, including
apoptosis, and the killing of HIV "marked" T helper cells by T-killer
cells, as well as possibly others. It has nothing to do with loss of genes.
>. Before the T-Cell disintegrates, the virus cuts itself into a whole
>bunch of little pieces. That's what's called "Reverse Transcriptase".
No, reverse transcriptase is the enzyme (actually two enzyme: a polymerase
and a robonuclease: the first "builds" the new DNA, the second degrades
the RNA post transcription) that copies viral RNA into DNA so that it can
be incorporated into the host nucleus.
> When
>the T-Cell disintegrates, all those pieces float free into the blood stream.
>Those little pieces are new viruses. Then the viruses go find new T-Cells
>to attack, and the cycle starts all over again.
Although viral budding can destroy a T-cell, this is not always the case,
and 99% of the cellular debris is not viral, but simply the "pieces"
of the T-cell.
There are many great resources on the net that explain viral life cycles.
I think one of the best "plain language" expositions is in the 1988
Issue of scientific american dedicated to HIV. It's a little out of
date now, but the basic principles of viral life cycle are still
viable.
There are also good basic resources at
http://www.thebody.com/whatis/underst.html
Good luck!
Carlton
_______________________________________________________________________
| |
| Carlton Hogan (carlton at gopher.ccbr.umn.edu) |
| Community Programs for Clinical Research on AIDS Statistical Center |
| Coordinating Center for Biometric Research |
| Division of Biostatistics, School of Public Health |
| University of Minnesota |
| 2221 University Ave SE, Suite 200 Voice: (612) 626 8899 |
| Minneapolis MN 55414 FAX: (612) 626 8892 |
|_____________________________________________________________________|
Affiliation Provided for Sake of Identification, not Representation
>>--
>> Axel Boldt ** axel at uni-paderborn.de **
>math-www.uni-paderborn.de/~axel/
>
