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Viruses: The only known case of HIV cure

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HIV is a cytopathic retrovirus – it carries its genetic information in RNA enclosed in a protein envelope surrounded by a heavy layer of glycosylation. The main target cells of the virus are CD4 T cells, also known as T helper cells. HIV glycoproteins gp120 and gp41 must bind the T cell’s CD4 receptor and a coreceptor to enable viral entry. Most often, this coreceptor is chemokine receptor 5 (CCR-5) coded for by the CCR-5 gene.
Figure 1 Basic structure of HIV virus; adapted from wikimedia image courtesy of the US National Institute of Health
Individuals homozygous or heterozygous for a mutation known as CCR-5Δ32 have shown resistance to certain strains of the virus. However, this mutation is only found in a small portion of the population. The mutated sequence is shown in Figure 2.
Figure 2 Nucleotide sequence of CCR-5 wildtype (WT) and CCR-5Δ32
The only case of HIV being cured is that of the so-called Berlin Patient. In 2006, about 10 years after discovering he had HIV, Timothy Ray Brown was diagnosed with acute leukemia while living in Berlin. As part of his cancer therapy, Mr. Brown received two stem cell transplants from a donor who was homozygous for the CCR-5Δ32 mutation. At this time, he also stopped taking his antiretroviral therapy (ART) treatment, yet within a year of the transplants, HIV was undetectable and the patient’s white blood cell counts drastically increased. His CCR-5 expression before and after stem cell transplantation is shown in Figure 3.
Figure 3 Gel electrophoresis of control and patient samples
Data adapted from: Hutter, G. (2009). Long-Term Control Of HIV ByDelta32/Delta32 Stem-Cell Transplantation. New England Journal of Medicine, 692-698. Liu R, Paxton WA et al. (1996). Homozygous defect in HIV-1 coreceptor accounts for resistance of some multiply-exposed individuals to HIV-1 infection. Cell, 86: 367-77.
What sort of mutation is CKR-5 Δ32?
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