Resistance to AIDS virus

[Jeffrey200]

Hi

I was reading recently about the gene that creates resistance to HIV in humans.  I gather up to 10-20% of the population can have the gene, and some have 2 copies which makes them very resistant to infection.  I found this website www.delta32.com.au and got tested.  It was really interesting to know I had a copy of the gene.  Anyway, thought this might be useful for people wanting to find out more about their genetic makeup.  I was wondering if anyone else has tried this test as well?

Jeff

[Ann]

Jeff,

You need to know that just because you have that gene doesn't mean you are totally immune to hiv infection. You need to be using condoms for anal or vaginal intercourse, every time, no exceptions until such time as you are in a securely monogamous relationship where you have both tested for ALL STIs together. To agree to have unprotected intercourse is to consent to the possibility of being infected with a sexually transmitted infection.

Have a look through the condom and lube links in my signature line so you can use condoms with confidence.

Please also read through the Welcome Thread so you can familiarize yourself with our Forum Posting Guidelines and also follow the Lessons links.

Ann

[NYER29]

I smell a scam here and it looks like someone is trying to peddle thier test on this website preying on the insecurities of myself and the rest worried folk on this board...

[scarycat]

No. It is not a scam. There was actually a documentary on PBS about the mutation. It is more prevalent in Europen populations because it also  provides some resistance to the plague.

[RapidRod]

It’s not an airtight guarantee of never getting AIDS. Some unusual types of HIV can use other proteins for entering cells. Rarely have there been people who have two mutant CCR5 genes who have died from AIDS.

Also, CCR5 is not the whole story of immunity to HIV infection. Some resistant people have been found who have two perfectly normal copies of CCR5. So other genes also contribute to slowing down HIV infection, and scientists are busy trying to identify them.

The usefulness of this work is mainly in how it helps us understand how the virus works and points to new possibilities for drugs to treat infection.

[HIVworker]

Rapid,

They are not so unusual. In AIDS, when viral replication is high, the virus becomes CXCR4 tropic and can infect cells other than CCR5 ones. If you are exposed to this virus and are homozygous for the delta-32 mutation, you would stand to get HIV.

Having one copy of delta-32 doesn't make you immune it just means that you are less likely to progress to AIDS as quickly. Two copies makes you more resistant but NOT immune. There are cases of homozygous Delta-32 people getting HIV. The progression is delayed in these patients, but they still got it.

R

[RapidRod]

That information came directly from the website he posted verbatim.

[Jeffrey200]

First of all, non-one was advocating unsafe sex (unless I miss-read something?).  Secondly, some facts on the issue:

Here's a published scientific review on the subject:

Host Genes and HIV: The Role of the Chemokine Receptor Gene CCR5 and Its Allele (D32 CCR5).  Janet M. McNicholl, Dawn K. Smith, Shoukat H. Qari, and Thomas Hodge.  Centers for Disease Control and Prevention, Atlanta, Georgia, USA  Emerging Infectious Diseases Vol. 3, No. 3, July–September 1997

This paper reviews the numerous studies on the delta32 mutation covering thousands of postive and negative individuals.  Here is a quote from the paper.

"Does the CCR5 32 Bp Deletion Provide Absolute
Protection Against HIV Infection?

The genetic link to remaining HIV-negative
in spite of continued HIV exposure was the
subject of much discussion during the summer
and fall of 1996. Was the protection absolute?
Who should be tested for the gene? Would
persons told they were homozygous for the deletion
engage in high-risk behavior more frequently?
Although at that point no one homozygous for the
deletion had been found HIV-positive, the fact
that CXCR4 gene and several other chemokine
receptors could mediate HIV entry suggested
caution in assuming that persons with the CCR5
D32/D32 genotype would be absolutely resistant
to HIV infection. Since then, three HIV infected
persons with this genotype have been reported"

So, whilst infection is possible, it is evidently a quite rare event.

Jeff

[ScienceGuy25]

First of all, non-one was advocating unsafe sex (unless I miss-read something?).  Secondly, some facts on the issue:

Here's a published scientific review on the subject:

Host Genes and HIV: The Role of the Chemokine Receptor Gene CCR5 and Its Allele (D32 CCR5).  Janet M. McNicholl, Dawn K. Smith, Shoukat H. Qari, and Thomas Hodge.  Centers for Disease Control and Prevention, Atlanta, Georgia, USA  Emerging Infectious Diseases Vol. 3, No. 3, July–September 1997

This paper reviews the numerous studies on the delta32 mutation covering thousands of postive and negative individuals.  Here is a quote from the paper.

"Does the CCR5 32 Bp Deletion Provide Absolute
Protection Against HIV Infection?

The genetic link to remaining HIV-negative
in spite of continued HIV exposure was the
subject of much discussion during the summer
and fall of 1996. Was the protection absolute?
Who should be tested for the gene? Would
persons told they were homozygous for the deletion
engage in high-risk behavior more frequently?
Although at that point no one homozygous for the
deletion had been found HIV-positive, the fact
that CXCR4 gene and several other chemokine
receptors could mediate HIV entry suggested
caution in assuming that persons with the CCR5
D32/D32 genotype would be absolutely resistant
to HIV infection. Since then, three HIV infected
persons with this genotype have been reported"

So, whilst infection is possible, it is evidently a quite rare event.

Jeff

Yes Jeff but the problem is exactly as HIV worker has already pointed out.  While it is common in certain populations to have one copy of the delta32 mutation it is exceedingly rare to have 2 copies or be homozygous for this mutation and one copy of the mutation won't prevent infection.

[ScienceGuy25]

On that note here's a paper that found similar incidences of the mutation in populations who were HIV- and HIV+  (ie having the mutation did not offer protection)

Homozygous delta 32 deletion of the CCR-5 chemokine receptor gene in an HIV-1-infected patient.

Balotta C, Bagnarelli P, Violin M, Ridolfo AL, Zhou D, Berlusconi A, Corvasce S, Corbellino M, Clementi M, Clerici M, Moroni M, Galli M.

Clinica delle Malattie Infettive, Universita di Milano, Ospedale Luigi Sacco, Italy.

BACKGROUND: Recent research has found that entry of non-syncytium-inducing (NSI), monocyte-macrophage-tropic HIV-1 isolates requires binding to both CD4 and CCR5 receptors, and that delta 32/delta 32 homozygous individuals are protected against infection. OBJECTIVE: To analyse the polymorphism of CCR-5 gene in HIV-1-infected and uninfected subjects. DESIGN AND METHODS: CCR-5 sequences were amplified by polymerase chain reaction (PCR) from DNA of peripheral blood mononuclear cells. Samples from 152 HIV-1-infected subjects and 122 uninfected controls were tested for the detection of the 32 base-pair deletion. HIV-1 phenotype was determined by viral isolation and MT-2 evaluation. RESULTS: The wild-type/delta 32 heterozygous and delta 32/delta 32 homozygous conditions were represented in 10.7 and 0.8% of healthy controls and in 9.8 and 0.7% of HIV-1-infected subjects, respectively. Of note, the delta 32/delta 32 deletion of the CCR-5 gene was detected by PCR and sequencing confirmed in a patient with progressive infection harbouring a clade B virus with SI phenotype. CONCLUSIONS: delta 32/delta 32 homozygosity for the CCR-5 gene does not confer absolute protection against HIV-1 infection, suggesting that either macrophage-tropic viral strains could use coreceptors other than CCR-5 or infect independently of the presence of a functional CCR-5 coreceptor. Alternatively, primary infection sustained by T-cell-tropic isolates, although exceptional, may occur.

[jkinatl2]

Its certainly good to see epidemiology bolstered by laboratory studies. the deconstruction of this genetic element, similar to the Long Term Non-Progressor studies, might eventually help us provide substantial, non-intrusive HIV prevention - particularly in developing nations where woman's rights to their bodies remains a significant issue.

[ScienceGuy25]

Definitly agree with you there - I can't help but have this feeling we are going to see some great strides made within the next 10 years - maybe i'm being overly optimistic but i think science and our understanding of immunology is finally getting advanced enough to really do something exceptional.

3rd worlds still present a major problem, unfortunately money=medicine but hopefully significant progress can be made on the home front and abroad.  One of my med school colleagues is has actually taken part in running a clinic overseas and i'm thinking about taking a couple months to go join the effort -  at least i can help with the lab work

[Jeffrey200]

Hi ScienceGuy,

I've got a couple of points in relation to your comments.  Firstly, agree with your first point that one copy provides little or no resistance to infection.  Although it will delay progression from HIV infection to AIDS.

On your second point that the delta32 mutation is "exceedingly rare".  I think this is a bit of hyperbole. "Exceedingly rare" is language that geneticists would use to describe mutations that are perhaps 1 in 20,000 in a human population.  Rather, the incidence of having 2 copies of the delta32 mutation is 1-2% of the  caucausion population.  And in fact, in sero-negative populations which are at high risk of HIV infection this rises as high as 30% of the population.  Examples of this are found in the San Fancisco gay population.  So, whilst the delta32 mutation may be of lesser (although not insignificant) interest to the general population it is represented more highly in some sub-groups for which it is relevant to their lifestyle.

Now your third point.  I quote you:  "On that note here's a paper that found similar incidences of the mutation in populations who were HIV- and HIV+  (ie having the mutation did not offer protection)".   If I read the article correctly 0.7% of say ~150 individuals studies is n=1.  Feel free to correct me here, but I don't think this generates much in the way of statistics.  Well its a "population" of 1 anyway.  So anyway,  the take-home message is that SI strains of HIV have the potential to infect people with 2 copies of the mutation.  My next question would be then what is the incidence of SI strains versus non-SI strains of HIV?

Interesting topic anyway
Jeff

[Jeffrey200]

Oh and one more thing - 1% of the population of the United States is 3 million people - fairly common I would say

[James67]

That sounds like an awful lot of people with the gene.  Does anyone know if the gene gives resistance to any other viruses?

James

[kevin]

In my virology class at UCLA, a professor of mine did mention that there are some people in Africa that are immune to HIV. And since all the science classes there promote evolution, he then said if the human population did come close to extinct, that the HIV-immune people might start the new human race [bottle-neck effect].

What are your thoughts?

[Ann]

James67,

Can I ask why you are using different usernames while posting to our forums? Thus far, you have also used Jeffrey200 - in fact, you started this thread.

Please realize that this kind of activity is disrespectful of other forum members, as well as our moderators. People spend a considerable amount of time helping others in these forums. Using multiple accounts is at the very least annoying, if not deceiving and disrespectful of others. It is also against our Terms of Membership which you agreed to when you became a member. This information is also contained within the Welcome Thread, which you should have read by now. So really, you have no excuse.

You must realize that the answers won't change, no matter how many names you post under.

I would appreciate a reply to this message, and I hope you will commit to using just one account - preferably your original one. If not, you will be banned from further access to the forums.

Ann