Stem cell transplantation of CCR5 DELTA 32 Gene

 One of the latest discoveries by using such techniques has revealed the Long-Term Control of human immunodeficiency virus (HIV) by CCR5 Delta32/Delta32 Stem-Cell Transplantation. HIV is a retrovirus (RNA virus) and its infection is one in the most pressing health issues facing the contemporary world.

Stem cell transplantation of CCR5 DELTA 32 Gene

AUTHORS: SARA ZAHID AND MARRIUM MUDASSAR

Since first reported case of HIV/AIDS in 1981, over 25 million people have died. Out of the millions of individuals infected every year with the HIV virus, a few have shown HIV/AIDS resistance.

 HIV virus attacks the immune system of human body making the body vulnerable to external infections and cancer. HIV interferes with bodily functions by combing to CD4 receptor of T lymphocyte and progresses by combining with CCR5 or CXCR4 co-receptor.

The CCR5 (C-C Chemokine Receptor type 5) gene is located at chromosome region 3p21.314 and comprises three exons, two introns and two promoters. It has been found that if a homozygous 32bp deletion in CCR5 allele is achieved, it can cause inactivity of CCR5 gene product resulting in high resistance against HIV-1 virus.

The Delta32 mutation at the CCR5 locus could be a well-studied example of survival of the fittest acting in humans. The mutation is found predominantly in Europe and western Asia, with higher frequencies typically within the north which occurred in the genomes of residents while facing the plague.

Professor Christopher Duncan and Dr. Susan Scott from the University’s School of Biological Sciences, whose analysis is printed within the March edition of Journal of Medical biological science, commented: “The fact that the CCR5-delta thirty two mutation is restricted to Europe suggests that the plagues of the center Ages contend a giant half in raising the frequency of the mutation. These plagues were conjointly confined to Europe, persisted for more than 300 years and had a 100% case mortality.”

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According to research published in new England journal of medicine by Gero Hütter, M.D.,Daniel Nowak, M.D., Maximilian Mossner, B.S., Susanne Ganepola, M.D. demonstrates that if stem cells from a donor who was homozygous for CCR5 delta32 mutation is transplanted in a patient with acute myeloid leukemia and HIV-1 infection. The patient remained without the reoccurrence of viral infection 20 months after transplantation and withdrawal of antiretroviral therapy showing that homozygous carriers of the Delta32 mutation are resistant to HIV-1 infection because this mutation hinders the practical expression of the CCR5 chemokine receptor.

With reference to an experiment carried out by Arne Müßig, M.D., Kristina Allers, Ph.D., Thomas Schneider, M.D., Ph.D., Jörg Hofmann, Ph.D., Claudia Kücherer, M.D., Olga Blau, M.D. it has been shown that the transplantation of CCR5 delta 32 stem cells led to complete chimerism(a single organism composed of cells with distinct genotypes), and the patient’s peripheral-blood monocytes changed from a heterozygous to a homozygous genotype regarding the CCR5 delta32 allele.

Although the patient had non–CCR5-tropic X4 variants and HAART (highly active antiretroviral therapy- combination drug therapies used to treat HIV) was discontinued for more than 20 months, HIV-1 virus could not be detected in peripheral blood, bone marrow, or rectal mucosa, as assessed with RNA and proviral DNA PCR assays (in vitro procedure used to detect, quantify and/or analyze the binding or movement of a biological molecule). For as long as the viral load continues to be undetectable, this patient will not require antiretroviral therapy.

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The research carried out by Gero Hutter of Department of Hematology and Christoph Lodennnkemper of research center of immune science reported the case of an HIV-infected patient in whom viral replication remained absent despite the termination of antiretroviral medical aid once transplanted with CCR5Δ32/Δ32 stem cells. However, it had been expected that the lasting microorganism reservoir would cause HIV rebound and infection progression throughout the method of immune reconstitution.

In a study carried out in 2010, effective re-formation of CD4+ T cells at the systemic level as well as in the gut mucosal immune system after CCR5Δ32/Δ32 stem cell transplantation, while the patient remains without any sign of HIV infection has been observed.

Though, recovered CD4+ T cells hold a high proportion of activated memory CD4+ T cells, i.e., the favored targets of HIV, and are liable to productive infection with CXCR4-tropic HIV. Furthermore, during the process of restoration of immune system, evidence for the replacement of long-lived host tissue cells with donor-derived cells was found, indicating that the size of the viral reservoir has been reduced over time. Results of this research strongly suggested that cure of HIV has been achieved in this patient.

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This discovery can revolutionized the world of today’s genetic therapy saving thousands of lives, giving hopeless the hope of survival and making patients to live their lives normally.  Mutation in CCR5 gene can not only save a person from the infection of HIV but also prevent a person from bone diseases hence it can be proven to be a great discovery in the field of biotechnology.

It presents possibilities for new ways to protect against HIV. Many wonder if genetic testing is out there, however to ascertain if one has the mutation. There are some tests available however it’s not widespread or widely encouraged. The mutation is not completely fool proof.

 Cases of homozygous carriers that have become infected with HIV have been reported. These few exceptions led to the discouragement of the health officials from fully supporting genetic tests over ethical concerns. It would not be wise for those with the mutation to assume that they can lead a dangerous lifestyle and remain healthy.

Further clear understanding of the causes of certain people being resistant to HIV/AIDS with the help of CCR5-32 Delta will hopefully lead to new and highly successful treatments in our lifetime and will open a new world for dealing with genetic diseases.

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