Genetic Protections against HIV

Infection Is Naturally Avoided due to Mutations

Feb 6, 2009 Alicia Mae Prater

AIDS is the final stage of HIV infection, which killed an estimated 2.1 million people in 2007, but some individuals have been found to be resistant to HIV/AIDS.

The human immunodeficiency virus (HIV) is a retrovirus spread by body fluids that come into contact with other body fluids – blood to blood contact, breast feeding, and sexual transmission. HIV attacks the cells of the immune system, particularly T cells, based on the proteins it recognizes on the cell surface. Viral replication destroys the T cells, spreading HIV throughout the system to further infect the T cells in the system. The only current treatment is antiretroviral therapy, which targets the enzymes specific to HIV replication.

Eventually, the T cells are depleted and immunodeficiency allows opportunistic infections to take hold in the infected individual. The occurrence of these opportunistic infections in the presence of anti-HIV antibodies and/or a low white blood cell count, the precursors to T cells, is AIDS – acquired immune deficiency syndrome. This is the final stage of HIV infection and results in death. There is no cure for the disease and it manifests differently in different patients.

HIV/AIDS Facts

The most recent AIDS epidemic update was released by UNAIDS, the UN program on HIV/AIDS, in 2007. At that time, an estimated 33 million people worldwide were living with HIV, 2.1 million of which are children. The agency estimated that 290,000 children died of AIDS in 2007, part of the approximately 2.1 million total patients whose deaths were attributed to the disease. The epidemiological data released in 2008 present a similar picture.

Various ethnic populations have been of interest because of an apparent resistance to HIV infection among some individuals. Receptors on the T cells have been considered potential genetic factors in this resistance.

Resistance to HIV/AIDS

Individuals who are resistant to HIV infection fall into two groups: highly exposed, sero-negative (ESN) and long-term non-progressors (LTNP).

Those in the ESN group are not infected with HIV despite repeated exposure to the virus, sometimes in the form of an HIV-positive partner. The individuals carrying such a designation fall into many categories of exposure that have made it difficult and unsuccessful to determine the genetic basis of their protection.

The LTNP group includes less than 2 percent of HIV-positive individuals. The individuals in this group are actually not resistant to HIV infection, but are resistant to the progression of the disease to AIDS. The patients are infected with HIV, but have almost indiscernible viral load and no immune deficiency.

Some genetic similarities between ESN and LTNP backgrounds are of interest in the search for new therapies. These include:

• The delta32 mutation of CCR5, the R5-HIV co-receptor
• Other CCR5 variants and polymorphisms (though some also result in increased progression)
• CCR2 variants
• CX3CR1 variants
• CXCR1 and CXCR2 locus
• Altered CXCR4 binding

For more information:

Arenzana-Seisdedos and Parmentier. Genetics of resistance to HIV infection: Role of co-receptors and co-receptor ligands. Seminars in Immunology, 18, 2006.

Piacentini et al. Genetic correlates of protection against HIV infection: The ally within. Journal of Internal Medicine, 265, 2008.

The copyright of the article Genetic Protections against HIV in Genetics & Evolution is owned by Alicia Mae Prater. Permission to republish Genetic Protections against HIV in print or online must be granted by the author in writing.

HIV

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