HIV coreceptor discussion

Andreas Weimann andi at chemie.fu-berlin.de
Wed Jan 26 20:23:14 EST 1994


smori at nmsu.edu (Shahram Mori) writes:


>Dear Immunetters
>Here is another problem that is worth discussing. Late last year Dr
>Hovanessian from Pateur Institute claimed that he had found the HIV
>coreceptor.However the HIV research community was extremely quick in crashing
>his idea.He claimed that CD-26 is also a cell surface protein that is
>responsible for HIV entry.I am a little confused about this. One evidence
>that was mentioned by Hovanssian was that potent inhibitors of CD-26
>enzymatic activity could also block HIV infection.The second line of evidence
>were from transfection experiments taht showed that mouse cells that could not
>normally be infected by HIV could be infected when both CD4 and CD 26 are 
>present and not each by themselves. The scientific community criticized this
>experiment saying that he can't be sure that the virus that he sees was
>replicated inside the cell or just the virus that was put in cell culture.
>Hovanessian disagrees because he used a strain that had a high replication
>rate which is easier to detect in a short time.
>What I have a problem with are the cells that can't be infected unless
>both of thses receptors are present. We all know that cells that lack CD4
>receptors can be infected by HIV. Thus the notion of Co-receptor is
>illogical in this respect.

For all the cell types which have so far been shown to be susceptible to 
HIV see the review by Jay LEvy in the March issue of the Microbiological 
Reviews.
It is true that the cells don't have to be CD4 positive since alternative 
mechanisms like entry via the Fc receptor or the Complement receptor have 
been shown to be a gate for the virus. 
THe main problem in the transfection experiments is their transient 
state. Hovanessian didn't make stable cell lines as Dr.Sodroski from 
Dana-Farber complained. I don't understand why Hovanessian didn't try to 
fuse a gp120 and gp41 bearing human cell with a murine CD4/CD26, CD4, or 
only CD26 bearing cell. He could have used a reporter gene construct like 
a beta-gal-LTR in the murine cell and a tat-Plasmid in the human one in 
terms of proving the fusion event.
By this means he has no problems of proving if and where some more virus 
might origin from...



I don't dicard the importance of 
CD 26 but as a
>receptor, I am not sure that I can accept  at this time. I was wondering also
>if CD-26 is a ubiquitous protein.

CD 26 is a Dipeptidylpeptidase, other names are DPP4 or THAM, and 
Thymocytes and T cells have been shown to be positive for this 
antigen.
More information about CD 26 you will find in the article by MARGUET ET 
AL., J.BIOL.CHEM., 1992, 267, 2200-2208.

Andreas


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        THE HIGHER THE LEVEL, THE GREATER THE CONFUSION


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