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Some of the research presented this week at the Seventh International
Conference on AIDS in Florence may be flawed because of the way HIV behaves
in the test tube.

A team of American scientists suspects that the age of HIV and the concentration
of human cells used as ‘targets’ for the virus could skew experimental results.
‘It’s not obvious,’ said Scott Layne of Los Alamos National Laboratory in
New Mexico. ‘As far as I know, this has never been an issue in virology.’

Layne, a physicist and physician, and his colleagues at the National
Institutes of Health have focused on CD4 proteins found on the surface of
cells of the immune system that fight infection. HIV homes in on CD4, attaches
its own ‘knobs’ of protein called gp120, and replaces the cell’s genetic
code with its own.

One way to fool HIV in infected people is to flood the immune system
with a solution of artificial CD4 (sCD4) to act as ‘red herrings’. But this
strategy has had mixed results in test tubes and humans. In practice, an
equilibrium develops between HIV and the sCD4 so that only some of the knobs
are covered.

Layne and his colleagues have discovered that as a virus ages, many
of its gp120 knobs fall off. At some threshold, the virus’s infectiveness
drops off sharply.

Researchers working with sCD4 note that laboratory strains of HIV are
the easiest to quell in the test tube, and strains taken direct from patients
are the hardest. Eric Daar, a researcher at Cedars-Sinai Medical Center
in Los Angeles, says there is a lot of merit in what Layne is saying.

Daar does standardise the age of his viral stock, but agrees that strains
vary in their affinity for immune cells. But age may not be the only factor.
Some strains may simply shed gp120 knobs faster, or sCD4 may induce them
to drop the knobs, he says. When Daar took a fragment of gp120 from viruses
that resist sCD4 treatment and attached it to vulnerable strains, the strains
became more resistant.

The process of treating immune cells with sCD4 and then challenging
them with HIV is also a problem, says Layne. With low concentrations of
target cells, sCD4 protects relatively well. That could be because the fewer
target cells there are, the less chance a virus has to find one before it
loses too many knobs to be potent. At high cell concentrations, even an
old virus has a better chance of finding prey.

Layne’s findings, published in the June issue of the Journal of Virology
(vol 65), could explain why people treated with sCD4 have not responded
well. Lymph nodes and organs are chock full of immune cells, so more blocking
agent would be needed there than in other parts of the body.