CCR5 rs333: Understanding the Delta 32 HIV-Resistance Variant
The rs333 variant, commonly known as the CCR5-Delta32 mutation, is a 32-base pair deletion in the CCR5 gene. This genetic change is widely studied for its role in providing strong resistance to HIV-1 infection in individuals who carry two copies of the deletion.
What each genotype means
Typical HIV susceptibility
This is the common form of the CCR5 gene, which produces a functional chemokine receptor protein. Individuals with this genotype do not have the protective 32-base pair deletion and remain susceptible to R5-tropic HIV-1 strains that use this receptor to enter cells.
This is the most common genotype globally, found in the vast majority of the human population.
Partial HIV resistance
Carrying one copy of the 32-base pair deletion (often called CCR5-delta32) may provide partial resistance to HIV-1 infection. Research suggests that this heterozygous state may also be associated with a delayed progression to AIDS if an individual becomes infected with HIV.
Carried by approximately 10% to 16% of people of Northern European ancestry, but is rare or absent in many other global populations.
What is the rs333 Variant?
The rs333 variant is a specific genetic deletion located within the CCR5 gene on chromosome 3. In this variant, a segment of 32 base pairs is missing from the DNA sequence. This deletion causes a frameshift in the genetic code, which prevents the cell from producing a functional CCR5 protein on the surface of immune cells. Because the CCR5 protein acts as a primary entry point for the HIV-1 virus to infect human cells, the absence of this receptor effectively blocks the virus from entering and infecting those cells. This variant is one of the most well-documented examples of a single genetic change having a profound impact on susceptibility to a specific infectious disease.
The Role of the CCR5 Gene
The CCR5 gene encodes a protein called C-C motif chemokine receptor 5. Under normal conditions, this protein functions as a receptor on the surface of white blood cells, particularly T-cells. It plays a critical role in the immune system by helping cells respond to chemokines, which are signaling molecules that guide immune cells to sites of infection or inflammation. While the CCR5 protein is essential for normal immune function, it is also exploited by HIV-1 as a co-receptor to gain entry into host cells. When the rs333 deletion is present, the resulting protein is truncated and fails to reach the cell surface. This structural change renders the cell resistant to R5-tropic strains of HIV-1, which rely on the CCR5 receptor for infection.
Research and Evidence
Scientific research has consistently shown that individuals who are homozygous for the rs333 deletion (carrying two copies) exhibit near-complete resistance to HIV-1 infection. Heterozygous individuals, who carry one copy of the deletion and one functional copy of the gene, may show some level of reduced susceptibility or slower disease progression, though the evidence for this is more nuanced. Beyond HIV, researchers have investigated whether this variant provides protection against other historical pathogens, such as the bubonic plague or smallpox, which may have driven its selection in European populations. However, the variant is not without potential trade-offs; some studies suggest that individuals with the deletion may have an increased risk of severe outcomes when infected with certain other viruses, such as the West Nile virus, highlighting the complexity of immune-related genetic variations.
Population Frequency
The frequency of the rs333 deletion varies significantly across different global populations. It is most commonly found in populations of Northern European descent, where the allele frequency can reach approximately 10% to 16%. In contrast, the variant is largely absent in native African, East Asian, and American Indian populations. This geographic distribution suggests that the mutation likely arose in the last few thousand years and was subject to strong selective pressures in ancestral European groups. Because of this uneven distribution, the protective effect associated with the variant is primarily relevant to specific ancestral backgrounds, and it is not a universal feature of human genetic diversity.
Interpreting Your Genetic Information
Understanding your status regarding the rs333 variant is a matter of scientific interest, but it should not be used to guide personal health decisions or replace standard medical advice. While the variant is associated with HIV resistance, it does not provide immunity to all strains of HIV, nor does it protect against other sexually transmitted infections or health conditions. If you are concerned about HIV risk or have questions about your health, it is essential to consult with a qualified healthcare provider or a clinical genetic counselor. They can provide context based on your full medical history and current clinical guidelines. Never use genetic test results to alter your behavior or ignore standard preventative health measures, as genetic information is only one piece of a much larger health puzzle.
How common is this variant?
The rs333 deletion is found in approximately 10% of Northern European populations, with frequencies declining toward Southeastern Eurasia and being virtually absent in African, East Asian, and American Indian populations.
Frequently asked questions
Does the CCR5-Delta32 mutation make me immune to HIV?
Individuals who are homozygous for the deletion (carrying two copies) are highly resistant to R5-tropic HIV-1 infection. However, it does not provide absolute immunity to all forms of the virus, and it does not protect against other infections.
Can I get tested for the rs333 variant?
Yes, this variant is included in many commercial genetic testing panels. However, you should discuss the implications of such testing with a healthcare professional to understand what the results mean for your specific health context.
Why is this variant more common in Europeans?
Evolutionary biologists believe the variant was subject to strong selective pressure in ancestral European populations, possibly due to historical epidemics like the bubonic plague or smallpox, which favored those who carried the mutation.
Are there any health risks to having the Delta32 mutation?
While the mutation provides resistance to HIV, some research suggests it may be associated with an increased risk of severe outcomes from other viral infections, such as the West Nile virus. It is a trade-off in immune system function.
Sources & further reading
Educational information only, last refreshed 10/9/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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