CCR5 and Protection from AIDS

James Howard jmhoward at sprynet.com
Tue Dec 8 13:04:49 EST 1998


Dr. Moné,

Again, you summarily dismiss my case that testosterone levels are involved
in vulnerability to HIV infection.  I guess I have to accept this.  Let’s
look at your latest criticisms of my posts.  You say: “The study you cite,
and its interpretations, in no way establishes a causal link between
testosterone levels and incidence of either HIV-1 infection or AIDS.” I
provided you with numerous studies, especially in my second post, all of
which point to support of my “hypothesis” of my original post.  Now, I have
to ask you, which “study… and its interpretations,” do you mean?  You then
ask: “Are castrated males more susceptible than their fertile counterparts?”
Well, in support of my hypothesis, I provided, in my second post, two
studies, in horses, which found that testosterone is directly involved in
infection and maintenance of the equine arteritis virus (J Comp Pathol 1994;
111: 383 and J Comp Pathol 1993; 109: 29).  I could not find any research on
castrated humans prior to being infected by the HIV, nor do I think anyone
will castrate any men, then infect them with the HIV.

You go on to say: “One could postulate that decreased estrogen production is
responsible for the higher incidence on [sic] NEW infections in males vs.
females.”  If your conjecture were correct, then white women should not
exhibit less HIV infection than black women, because black women produce
significantly more estrogen than white women (J Natl Cancer Inst 1996; 88:
1369).   As I pointed out in my second post, white women exhibit less HIV
infection than black women; the supporting citation is in that post.  You
then say: “Or perhaps menstrual cycles are the answer.  Again just because
event A precedes event B, it doesn’t mean that A causes B!”  When I first
identified my post as a “hypothesis,” I think it goes, without saying, that
I am suggesting that a causal relationship exists.  I also understant that
the word “hypothesis” implies that it might not mean that it is true.  Thank
you for explaining that a hypothesis is not necessarily true.  Also, I want
to thank you for your professorial remarks:  “Biology is seldom as simple as
a one to one relationship.  There can be no doubt that susceptibility to HIV
infection, as well as rate of progression to disease is a function of many
different factors, some specific to the individual host, and some specific
to the virus.”  Ipso facto…

Your next statement is: “To date, the CCR5 et al. story provides the only
rigorously tested identification of a genetic factor which alters the
progression of AIDS.”  While your statement is correct, you should be aware
one report concludes that “there is no geographic clustering of CCR5
polymorphism in different ethnic populations, suggesting that CCR5 diversity
is not the underlying explanation for differences in the spread of different
HIV-1 subtypes.” (AIDS Res Hum Retroviruses 1997; 13: 1357).  In my original
post, I provide two citations, J Med Virol 1998; 55: 147 and AIDS Res Hum
Retroviruses 1997; 13: 1583, which show that chimpanzees carry intact CCR5
and CXCR4 receptors which can bind the HIV vis-à-vis the difficulty in
infecting chimpanzees with the HIV.  I pointed out that chimpanzees produce
more DHEA and less testosterone than humans.  My opening statements of my
original post says:  “It is my hypothesis that vulnerability to HIV
infection and AIDS results from low dehydroepiandrosterone (DHEA).
Furthermore, it is my hypothesis that testosterone interferes with the
availability of DHEA.”  Your next statement is not necessarily true: “If
testosterone levels are truly significant, it would be relatively simple to
produce the evidence which could withstand peer review.  I have yet to see
this evidence.”  If testosterone is involved, one could use chimps and/or
humans.  The chimps would have to be treated in utero, as well as throughout
life to maybe produce a testosterone effect similar to human males.  As I
pointed out above, the human experiments would have to involve castration,
at various ages, then exposure to the HIV.  I suggest that the studies I
have reproduced in my two posts go very far in supporting my hypothesis,
until the two unlikely possibilities, just mentioned, occur.


"James P. Mone" wrote in message ...
>James,
>The study you cite, and its interpretations, in no way establishes a
>causal link between testosterone levels and incidence of either HIV-1
>infection or AIDS. Are castrated males more susceptible than their fertile
>counterparts?   One could postulate that decreased estrogen production
>is responsible for the higher incidence on NEW infections in males vs
>females.  Or perhaps menstrual cycles are the answer.  Again just because
>event A precedes event B, it doesn't mean that A causes B!
>
>Biology is seldom as simple as a one to one relationship.  There can be no
>doubt that susceptibility to HIV infection, as well as rate of progression
>to disease is a function of many different factors, some specific to the
>individual host, and some specific to the virus.  To date, the CCR5 et al.
>story provides the only rigorously tested identification of a genetic
>factor which alters the progression of AIDS.  If testosterone levels are
>truely significant, it would be relatively simple to produce the evidence
>which could withstand peer review.  I have yet to see this evidence.
>
>Jay M.C
>
>
>





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