11.5 Mutations  (Page 2/14)

A beneficial mutation

Since the first case of infection with human immunodeficiency virus (HIV) was reported in 1981, nearly 40 million people have died from HIV infection, World Health Organization. “ Global Health Observatory (GHO) Data, HIV/AIDS.” http://www.who.int/gho/hiv/en/. Accessed August 5, 2016. the virus that causes acquired immune deficiency syndrome (AIDS). The virus targets helper T cells that play a key role in bridging the innate and adaptive immune response, infecting and killing cells normally involved in the body’s response to infection. There is no cure for HIV infection, but many drugs have been developed to slow or block the progression of the virus. Although individuals around the world may be infected, the highest prevalence among people 15–49 years old is in sub-Saharan Africa, where nearly one person in 20 is infected, accounting for greater than 70% of the infections worldwide World Health Organization. “ Global Health Observatory (GHO) Data, HIV/AIDS.” http://www.who.int/gho/hiv/en/. Accessed August 5, 2016. ( [link] ). Unfortunately, this is also a part of the world where prevention strategies and drugs to treat the infection are the most lacking.

In recent years, scientific interest has been piqued by the discovery of a few individuals from northern Europe who are resistant to HIV infection. In 1998, American geneticist Stephen J. O’Brien at the National Institutes of Health (NIH) and colleagues published the results of their genetic analysis of more than 4,000 individuals. These indicated that many individuals of Eurasian descent (up to 14% in some ethnic groups) have a deletion mutation, called CCR5-delta 32, in the gene encoding CCR5. CCR5 is a coreceptor found on the surface of T cells that is necessary for many strains of the virus to enter the host cell. The mutation leads to the production of a receptor to which HIV cannot effectively bind and thus blocks viral entry. People homozygous for this mutation have greatly reduced susceptibility to HIV infection, and those who are heterozygous have some protection from infection as well.

It is not clear why people of northern European descent, specifically, carry this mutation, but its prevalence seems to be highest in northern Europe and steadily decreases in populations as one moves south. Research indicates that the mutation has been present since before HIV appeared and may have been selected for in European populations as a result of exposure to the plague or smallpox. This mutation may protect individuals from plague (caused by the bacterium Yersinia pestis ) and smallpox (caused by the variola virus) because this receptor may also be involved in these diseases. The age of this mutation is a matter of debate, but estimates suggest it appeared between 1875 years to 225 years ago, and may have been spread from Northern Europe through Viking invasions.

This exciting finding has led to new avenues in HIV research, including looking for drugs to block CCR5 binding to HIV in individuals who lack the mutation. Although DNA testing to determine which individuals carry the CCR5-delta 32 mutation is possible, there are documented cases of individuals homozygous for the mutation contracting HIV. For this reason, DNA testing for the mutation is not widely recommended by public health officials so as not to encourage risky behavior in those who carry the mutation. Nevertheless, inhibiting the binding of HIV to CCR5 continues to be a valid strategy for the development of drug therapies for those infected with HIV.