Scientists modify induced pluripotent stem cells with CCR5delta32 mutation to slow disease progression in T cells during HIV infection
The human immunodeficiency virus (HIV) needs to convert its RNA into DNA prior to hijacking the host cell’s machinery in order to multiply and release virus particles. Curiously, the virus is armed with an enzyme that is prone to error when converting viral RNA into DNA. The result of this is a swarm of virus particles in the host that are genetically related but unalike.
There is consequently a changing landscape in HIV genetics during the course of an infection. One associated feature is that of a modification in the door that the virus uses to enter host cells. CCR5-tropic virus particles are present at the onset of an infection. They use the CCR5 receptor present on T cells, monocytes, and macrophages, to enter the host cell. Later, the CXCR4-tropic viruses emerge at the advanced disease stage and infect T cells but not macrophages.
There is a naturally present mutation in the CCR5 gene in a small percentage of the population. What is intriguing is that this mutation does not render any disease. Rather, the presence of this mutation on both copies of the gene in homozygous individuals makes them immune to HIV infection. And when only one copy of the gene is present in heterozygous individuals, the progression of the disease is slow thereby promoting a longer lifespan in HIV-positive persons.
Obviously, the presence of the CCR5delta32 mutation on CCR5 receptors has potential. It could make T cells and macrophages immune to HIV infection or slow down disease progression. Scientists have devised a plan to exploit this mutation for therapeutic benefit to HIV patients as follows:
- Take blood sample from the patient Introduce genes to convert blood cells into stem cells (induced pluripotent stem cells, iPSC)
- Use molecular biology technology to introduce the CCR5delta32 mutation into iPSC
- Use molecular biology assay to perform “quality assurance” testing of mutated iPSC
- Culture the iPSC to generate cells to transplant into the patient
- Ameliorate HIV infection in the patient by transplanting his/her mutated stem cells
While this technology is not clinically available yet, scientists have tested the proof of concept. They have gone as far as culturing the mutated stem cells and differentiating them into monocytes and macrophages and shown these PBMCs to be resistant to HIV infection.
We applaud the progress made towards the fight against HIV. HemaCare provides disease state T cells as well as disease state cells from HIV patients to further the work towards finding the cure for HIV.
1. Ye L, Wang J, Beyer AI, et al. Seamless modification of wild-type induced pluripotent stem cells to the natural CCR5Δ32 mutation confers resistance to HIV infection. Proc Natl Acad Sci U S A. 2014 Jun 9. [Epub ahead of print] PubMed PMID: 24927590.