Does HIV kill cells?

John Ladasky ladasky at leland.Stanford.EDU
Thu Mar 24 04:39:16 EST 1994


In article <1994Mar24.085208.16835 at leeds.ac.uk>,
Ezekial <mic2mcb at gps.leeds.ac.uk> wrote:
>Can anyone out there resolve an apparent contradiction in the courses I'm
>currently doing? The virology course says that retroviruses don't kill their
>host cells except when its HIV in which case it does. Immunology says HIV
>doesn't kill cells, cytotoxic T cells doing their proper job remove the
>infected cells? Which is correct or is the fact that we don't actually know?

	Most of what I'm reading these days suggests that the majority of
CD4 cell death that occurs in AIDS is not the consequence of direct infection
by the virus.  In fact, it's currently believed that only about one CD4 cell
in a thousand is infected with HIV in an AIDS patient.  So why does an AIDS
patient's T cell count drop to near-zero?

	I've heard of two mechanisms by which indirect cell death might occur
in AIDS.  The first involves soluble gp120.  It turns out that the gp120 en-
velope protein of HIV is *sparingly* soluble.  It has been shown that, if 
you crosslink CD4 molecules on a T cell without also crosslinking CD3 and the
T cell receptor, you get apoptosis rather than proliferation.  AIDS patients
do generally exhibit antibodies to gp120, so the crosslinking of CD4 could
occur through a complex of gp120 molecules and anti-gp120 antibodies. 

	The other mechanism of indirect cell death that is under considera-
tion is mediated by TNF.  Under the chronic inflammatory conditions seen in 
AIDS, there's a lot of TNF floating around.  TNF is well known to induce
apoptosis.

	My guess is that HIV doesn't kill its *host* cells.  However, ancil-
lary processes that result from HIV infection kill other cells that *could*
host HIV if virions ever got near them.  In each mechanism considered above
it is hypothesized that macrophages will eliminate the apoptotic T cells.

	Sorry, I'm at home now and don't have the references handy.  But
there is a nice mini-review/commentary article in a recent Immunology Today
called, "Immune Response to HIV - Helpful or Harmful?"  It covers the gp120/
anti-gp120 hypothesis.

>Matthew, mic2mcb at south-01.novell.leeds.ac.uk
>	 mic2mcb at gps.leeds.ac.uk

	Hope this was helpful (and maybe even correct??? What do you want
from a first-year grad student?)

							   - John Ladasky




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