HIV immunity may stem from ancient smallpox

Gannett News Service via The Arizona Republic ^ | Feb. 20, 2004 12:00 AM | Randy Dotinga

[muawiyah]

The immunity is hypothesized to have to do with the method used by the HIV viruses, or by several bacteria, and yet other viruses, to infect the host cell.

Smallpox, black plague, HIV and cholera, among others, use the same or very similar, pathway. I know that I am naturally immune to cholera but I'm not going to do an experiment to see if I am immune to HIV, or smallpox!

[VadeRetro]

My theory - which is only a WAG - is that some strain of SIV or HIV was pandemic among the ancestors of European humans a very, very long time ago, which explains the 15% heterozygous prevalence of the CCR-5 Delta 32 deletion in Europeans better than smallpox or plague.

I don't think that scenario produces the picture we have. Neither apparently do most scientists. Most people still don't have the virus, but if its ancestor had been in Europeans long ago, all people of European descent would have some form of it.

[VadeRetro]

Most people still don't have the virus, but if its ancestor had been in Europeans long ago, all people of European descent would have some form of it.

... Or they'd have the immunity, I should have said. Introduced in humans in pre-tech times, the virus would have created a huge death rate until either 1) a milder form of the virus evolved or, 2) humans with the immunity mutation were the most common kind of people around.

We don't all have the mutation (most of us have neither the mutation nor the virus), the virus has a high virulence, and genetic analysis points to a recent introduction in humans.

[CobaltBlue]

Most people still don't have the virus, but if its ancestor had been in Europeans long ago, all people of European descent would have some form of it.

Like we all have some form of smallpox?

[VadeRetro]

I wonder if an analysis of the simian virus family would point to a recent intro as does the human one. The reverse of your funny coincidence is that dusky mangabys got one strain of human viruses from humans at almost the same time chimps got another strain of human virus. But what if there are equally unrelated strains in, say, gorillas that have no human counterpart? (Don't know if it's true, just wondering.)

Or are you saying that humans did get the thing from primates, only some time in the far past? Why then don't Africans show the immunity?

[CobaltBlue]

Regardless, so far the only disease the CCR5-Delta 32 deletion is known to protect against is HIV-1. So far, they've tested it in association with hepatitis C, rheumatoid arthritis, diabetes, multiple sclerosis, Crohn's disease, myocardial infarction, and has been discounted in all but MI.

But who knows, I could be wrong.

[CobaltBlue]

Why then don't Africans show the immunity?

Maybe they are descended from populations which were not exposed to the virus. Or maybe CCR5-delta 32 deletion confers extra susceptibility to something else in Africa.

Or maybe CCR5-delta 32 deletion immunity is associated with another virus which recombined with SIV before it became HIV.

[CobaltBlue]

Maybe chimps and dusty mangabeys both got a human virus from Europeans which recombined in both to make SIV/HIV-1 and SIV/HIV-2, respectively? Something as innocuous to us as the common cold?

This is a total WAG but I was wondering when SARS did not break out into Europeans whether there was something similar going on.

[VadeRetro]

This story points to evidence that "a boom in bushmeat" is creating opportunities for species-jumping. Also, lots of SIV genetic diversity.

[Doctor Stochastic]

One point about smallpox as compared to plague is that the smallpox agent is a virus and plague is a bactium (New Mexico, Land of the Flea, Home of the Plague.) AIDS is virally caused so one would expect that smallpox defence may be of more use than a plague defence. Still, I don't know how close HIV is to smallpox.

[Doctor Stochastic]

Viruses have mutated in historical times to infect other animals. Feline panleukemia virus mutated in the 1970s to be able to infect dogs (under the name canine parvo virus.) (An example of a favorable mutation.)

[Jorge]

All those with the immunity share a pair of mutated genes that prevent their immune cells from developing a "receptor" that lets the virus break in. Researchers liken the receptor to a lock that viruses pick open; if the lock isn't there, the viruses can't enter.
The protection isn't absolute, however. HIV has managed to infect a tiny number of people who share the mutation, according to Mosier.

Interesting. I know some HIV positive people who have been infected for 10+ years and have not gotten sick, and don't take any meds.

I wonder if this mutation might offer varying degrees of protection against HIV.

[jennyp]

I suppose they could test tissue from people carrying what is believed to be genetic immunity to HIV to see if they are immune to cowpox - if that's been tried I haven't seen it.

Apparently they're going to try something similar...

The next step is to look at disease such as smallpox and perhaps cholera, he says. Researchers plan to see if the mutation protects mice from mousepox, a relative of smallpox in humans.

[Junior]

VadeRetro:  And humans are one of the least genetically diverse species of animals on the planet.

Not that I'm aware of. Could you please provide a pointer to support for this?

Over the past several years, since work began on the Human Genome Project, it's become apparent that there is not much genetic diversity between any two human beings on this planet.  Indeed, most of the sources I've found on the internet peg the diversity at 10 to 15 percent.

Geneticist figure we went through a population bottleneck sometime in the last 100,000 years.  There is strong evidence that ties this bottleneck to the Toba supervolcano eruption about 70,000 years ago.  The human population was reduced to a few thousand individuals (about 10,000 to 40,000, though some estimates put the figure as low as 2,000).

• Late Pleostocene Human Population Bottlenecks/Volcanic Winter, and Differentiation of Modern Humans
• Genetic Evidence/Present-Day DNA
• Paleoanthropology in the 1990s/Essays by James Q. Jacobs
• Ancient 'Volcanic Winter' Tied To Rapid Genetic Divergence In Humans
• Chimpanzee Subspecies Are Genetically Mixed And More Diverse Than Humans

[AdmSmith]

I know that I am naturally immune to cholera

Several studies (reviewed by Glass et al., 1985) indicated that individuals with blood group O are at higher risk of contracting cholera (due to Vibrio cholerae 01) than those with other blood groups and that individuals with blood group AB are relatively resistant to cholera. Clemens et al. (1989) demonstrated that individuals with blood group O are at higher risk for cholera due to only the E1 Tor biotype of V. cholerae 01. During a large field trial in Bangladesh of killed oral cholera vaccine, persons with blood group O were significantly less protected against severe cholera than were persons with AB blood group. Faruque et al. (1994) found that patients in Bangladesh who had diarrhea due to V. cholerae 0139 were nearly twice as likely as controls to be of blood group O (64 vs 34%) and that individuals with blood group AB were at no risk for diarrhea due to V. cholerae 0139. Individuals with blood group O were the most susceptible to diarrhea due to V. cholerae 0139, followed in order by groups B, A, and AB.

[AdmSmith]

Sorry I missed the ref: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?cmd=entry&id=110300

[muawiyah]

Reviewing this thread from 2004 to see if modern science has caught up to the reasons reindeer have red noses ~ and lo and behold you've asked your question twice and the answer is ~ the gene for protection is an autosomal recessive.

That means that protection is passed on to only 3/4 of descendants. 1/4 are left unprotected. As long as no epidemics come around eventually a large percentage of your population does not have the protective gene ~ and so they die.

In a number of cases it is disadvantageous to inherit the autosomal recessive protective gene from both parents. They die shortly after birth (under paleolithic conditions) ~ or in modern times they don't die right away but suffer as with cystic fibrosis, or sickle cell disease. With CF the current belief is that this is the gene that saves some humans from the ravages of the black plague. With sickle cell, that protects against malaria.

Like a time machine eh!