Author:
Nilavar Namrata M.,Paranjape Amita M.,Raghavan Sathees C.
Abstract
AbstractHIV is a retrovirus that infects CD4+ T lymphocytes in human beings and causes immunodeficiency. In the recent years, various therapies have been developed against HIV, including targeting the HIV specific protein, integrase, responsible for integration of HIV cDNA into host DNA. Although, integrase is specific to HIV, it has functional and structural similarity with RAG1, one of the partner proteins associated with V(D)J recombination, a process by which immune diversity is generated in humans. Currently, there are three HIV integrase inhibitors: Elvitegravir, Dolutegravir, and Raltegravir, in the market which have been approved by the FDA (USA). All three drugs are used in anti-retroviral therapy (ART). Previously, we showed that amongst the HIV inhibitors, Elvitegravir could significantly decrease B cell maturation in vivo and inhibit the physiological activities of RAGs in vitro, unlike Raltegravir. In the present study, we address the effect of second-generation integrase inhibitor, Dolutegravir on RAG activities. Binding and nicking studies showed that, Dolutegravir could decrease the binding efficiency of RAG1 domains and cleavage on DNA substrates, but not as considerably as Elvitegravir. Thus, we show that although the integrase inhibitors such as Elvitegravir show an affinity towards RAG1, the newer molecules may have lesser side-effects.
Funder
Council of Scientific and Industrial Research
Department of Atomic Energy, Government of India
Department of Biotechnology, Ministry of Science and Technology
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Cell Biology,Cellular and Molecular Neuroscience,Immunology
Cited by
10 articles.
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