HIV Resistant Mutation

HIV virus is one of the most pressing health concerns facing the modern world. Since the first reported case of HIV/AIDS in 1981, over 25 million people have died. Out of the millions of people infected each year with the HIV virus, a few have shown HIV/AIDS resistance. A genetic mutation found mostly in people of European descent delays the progression of AIDS and in some cases even brings about immunity.

HIV is the virus that causes the syndrome AIDS, which stands for acquired immune deficiency syndrome. Once infected with HIV a person can live many years without developing AIDS. After a person is infected with HIV, the virus seeks out the body's immune cells and attaches itself to them in the hopes of producing more virus particles. HIV's "main target" are CD4 immune cells. In the acute stages of infection the virus destroys a lot of CD4 cells and produces many virus particles. In turn the immune system goes into overdrive to try and ward off infection. After the acute stage the virus enters into a period of clinical latency that can last many years. During this time the virus is active but reproduces minimally. In the last stage of infection, AIDS, the number of CD4 cells drops well below the normal level. The body's immune system is left critically damaged, leaving the person susceptible to illness.

A genetic mutation known as CCR5-delta 32 is responsible for the two types of HIV resistance that exist. CCR5-delta 32 hampers HIV's ability to infiltrate immune cells. The mutation causes the CCR5 co-receptor on the outside of cells to develop smaller than usual and no longer sit outside of the cell. CCR5 co-receptor is like door that allows HIV entrance into the cell. The CCR5-delta 32 mutation in a sense locks "the door" which prevents HIV from entering into the cell. 1% of people descended from Northern Europeans, particularly Swedes, are immune to HIV infection. These lucky people are homozygous carriers of the mutated gene - meaning that they inherited a copy from both of their parents. Another 10 -15% (the number has even suggested to be 18%) of people with European heritage inherited one copy of the gene. Just one copy of the mutation does not prevent against infection. It does however reduce carrier's chances of infection and delays the progress of AIDS. Since the CCR5-delta 32 is tied primarily to the Eurasia region, the mutation has not been found in Africans, East Asians, or Amerindians.

Why does the CCR5-delta 32 mutation appear in people of European descent only? There is no solid answer to this question yet but many theories have been suggested. What researchers do know is that the mutation has been in the population longer than HIV has been infecting people. How long the mutation has been in humans varies depending on which scientist you ask. Estimates range from 700 to 2900 years. One hypothesis suggests that the mutation originated in the Vikings. Researchers noticed that the mutation exhibits a north-to-south cline. The gene appears more frequently in Northern Europeans than it does in Southern Europeans. Some scientists attribute this pattern to the Viking invasions. It is estimated that the allele was present in Scandinavia 1,000 to 1,2000 years

agoThrough their many invasions, the Vikings spread the allele from Scandanavia to Iceland, Russia, and central and southern Europe. For a mutation to become prevalent in a population there has to be a beneficial reason for having it. Otherwise the mutation would not be passed down generation after generation. Along this line of reasoning scientists have suggested that past epidemics were the driving force behind the prevalence of the mutation in Europeans. Scientists hypothesize that the mutation gave some sort of advantage to people against the epidemic. This gave these individuals an increased chance of survival and ability to reproduce and pass on the affected allele. Evidence dating the mutation back 700 years ago coincides perfectly with the Black Death. According to this idea, the Black Death drove natural selection in the human population. Those with the mutation were more likely to survive the plague and pass on their genes than those without which caused an increase in the percentage of people with the mutation. Smallpox is another epidemic that has been suggested. Those in favor of smallpox have continuity on their side. Unlike the Black Death, smallpox "has been continuous [for the last 700 years]" says Alison Galvani, a Yale University professor of epidemiology. Galvani notes that smallpox's longevity provided a reason for the mutation to continue throughout the generations. HIV and smallpox also share an important similarity. Both utilize the CCR5 receptor to infiltrate other cells. Coincidence? I don't know. But it is interesting to think that the mutation could have appeared several hundred years ago as a protective means against smallpox, survived through the generations, and then by chance have the ability to also provide HIV resistance.

CCR5-32 Delta is exciting. It presents possibilities for new ways to protect against HIV. Many wonder if genetic testing is available yet to see if one has the mutation. There are some tests available (just google CCR5-32 Delta testing and you'll see) but it is not yet widespread or widely recommended. The mutation is not completely fool proof. Cases of homozygous carriers that have become infected with HIV have been reported. These few exceptions have dissuaded health officials from fully supporting genetic tests over ethical concerns. It would not be wise for those with the mutation to assume that they can lead a dangerous lifestyle and remain healthy. Understanding how and why certain people are resistant to HIV/AIDS with the help of CCR5-32 Delta will hopefully lead to new and highly successful treatments in our lifetime.

References:

Dotinga , R. "Genetic HIV Resistance Deciphered." Wired. January 7, 2005.

Evolution. Double Immunity (2001).

The Tech Museum of Innovation. The Evolving Genetics of HIV (2013).

Novembre, J., Galavani, A., and Slatkin, M. The Geographic Spread of the CCR5 Δ32 HIV-Resistance Allele. PLOS Biology (2004)

Science Daily. "Biologists Discover Why 10 Percent Of Europeans Are Safe From HIV Infection."Science Daily. April 3, 2005.

Cohn, S.K. and Weaver, L.T. The Black Death and AIDS: CCR5-Δ32 in genetics and history. QJM 8, 497 - 503 (2006).

Aids.Gov. Stages of HIV (2013).

Images:

HIV Virions. CDC.

Pleiotrope (via Wikimedia Commons).