The Molecules of HIV

Note: this site last updated in 2006

delta32

An article from "The Molecules of HIV" (c) Dan Stowell
www.mcld.co.uk/hiv

A small fraction of the population carries a mutation in their CCR5 gene, called the Delta32 mutation. This mutated version of the gene produces malformed CCR5 proteins, which are useless as HIV coreceptors.

We each carry two copies of (most of) our genes - one copy from the mother, one from the father. If only one of a person's CCR5 genes is a Delta32 mutant (if they are "heterozygous" for the mutation - around 10% of the population are), they will have a partial resistance to HIV infection as a result. If both copies are Delta32 mutants (if the person is "homozygous" for CCR5-Delta32 - around 1% of the population are), then none of the CCR5 on that person's cells can help HIV enter, and the person is broadly resistant to HIV strains which require CCR5.

Remember, though, that not all HIV strains use CCR5 as a coreceptor. Even people who are homozygous for this mutation need to take care not to expose themselves to risk of HIV infection.

Therapies based on delta32?

Many people are researching the implications of delta32, and trying to develop therapies or prevention strategies which can make use of the knowledge of the effect delta32 has on HIV. But a "replication" of the effect of delta32 is not coming along any time soon, and the reason is that it's not a specific molecule or chemical in itself. "delta" just means there's a deletion somewhere in the CCR5 gene (and "32" tells us where!) - a "character" from the code has been deleted. This means that the product of the CCR5 gene is a slightly different molecule, for "delta32 people".

To create this difference in people without delta32 would be incredibly difficult - would we modify the CCR5 gene in every single cell in a person's body? (The answer is no, there's no way of doing that.) Would we inactivate the "normal" CCR5 and supply some alternative source of delta32-CCR5 molecules? (Perhaps, but again that's highly implausible with today's technology.)

So delta32 is interesting - and fortunate for some people - but there's currently no obvious way to turn it directly into a prevention/cure. One possible avenue of research seems to raise the possibility that we could induce a protective mutation in people - follow the link to read about that.

More information:

  • Eugen-Olsen J, Iversen AKN, Garred P et al. Heterozygosity for a deletion in CKR-5 gene leads to prolonged AIDS-free survival and slower CD4 T-cell decline in a cohort of HIV-seropositive individuals. AIDS 1997, 11: p305-10
  • AIDS Weekly news article: www.aegis.com/pubs/aidswkly/2001/AW010906.html

Written by
Dan Stowell
(©2002-2006)

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