APOBEC3G cytidine deaminase inhibits retrotransposition of endogenous retroviruses.
ABSTRACT Endogenous retroviruses are multicopy retroelements accounting for nearly 10% of murine or human genomes. These retroelements spread into our ancestral genome millions of years ago and have acted as a driving force for genome evolution. Endogenous retroviruses may also be deleterious for their host, and have been implicated in cancers and autoimmune diseases. Most retroelements have lost replication competence because of the accumulation of inactivating mutations, but several, including some murine intracisternal A-particle (IAP) and MusD sequences, are still mobile. These elements encode a reverse transcriptase activity and move by retrotransposition, an intracellular copy-and-paste process involving an RNA intermediate. The host has developed mechanisms to silence their expression, mainly cosuppression and gene methylation. Here we identify another level of antiviral control, mediated by APOBEC3G, a member of the cytidine deaminase family that was previously shown to block HIV replication. We show that APOBEC3G markedly inhibits retrotransposition of IAP and MusD elements, and induces G-to-A hypermutations in their DNA copies. APOBEC3G, by editing viral genetic material, provides an ancestral wide cellular defence against endogenous and exogenous invaders.
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ABSTRACT: The Apolipoprotein B mRNA-editing catalytic polypeptide-like 3 (APOBEC3) genes are able to inhibit the replication of a wide range of exogenous retroviruses, as well as endogenous retroviruses and retrotransposons. Three APOBEC3 genes, named APOBEC3Z1, APOBEC3Z2 and APOBEC3Z3, have been described in sheep. In this work the three genes have been screened in order to identify polymorphisms. No polymorphism was detected for the A3Z2 and A3Z3 genes but 16 SNPs and a 3-bp deletion were found in the A3Z1 gene. A thermoestability prediction analysis was applied to the detected amino acidic SNPs by three different programs. This analysis revealed a number of polymorphisms that could affect the protein stability. The SNPs of the 3'UTR were tested to detect alterations on the predicted microRNA target sites. Two new microRNA target sites were discovered for one of the alleles. Two SNPs were selected for association studies in relation with the retroviral disease Visna/Maedi in Latxa and Assaf sheep breeds. Although association analyses resulted unconclusive, probably due to the unsuitability of the SNP allele frequency distribution of the selected polymorphisms in the analyzed breeds, these genes remain good candidates for association studies. Copyright © 2014 Elsevier B.V. All rights reserved.Veterinary Immunology and Immunopathology 11/2014; 163(3-4). · 1.75 Impact Factor
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ABSTRACT: Development of an effective vaccine against HIV-1 is a major challenge for scientists at present. Rapid mutation and replication of the virus in patients contribute to the evolution of the virus, which makes it unconquerable. Hence a deep understanding of critical elements related to HIV-1 is necessary. Errors introduced during DNA synthesis by reverse transcriptase are the primary source of genetic variation within retroviral populations. Numerous current studies have shown that apolipo protein B mRNA-editing enzyme-catalytic polypeptide-like 3G (APOBEC3G) proteins mediated sub-lethal mutagenesis of HIV-1 proviral DNA contributes in viral fitness by accelerating human immunodeficiency virus-1 evolution. This results in the loss of the immunity and development of resistance against anti-viral drugs. This review focuses on the latest biological, biochemical, and structural studies in an attempt to discuss current ideas related to mutations initiated by reverse transcriptase and APOBEC3G. It also describes their effect on immunological diversity and retroviral restriction, and their overall effect on the viral genome respectively. A new procedure for eradication of HIV-1 has also been proposed based on the previous studies and proven facts. Citation: Soni RK, Kanampalliwar A, Tiwari A (2013) Role of Reverse Transcriptase and APOBEC3G in Survival of Human Immune Deficiency Virus -1 Genome. Virol Mycol 3: 125. doi:10.4172/2161-0517.1000125 Copyright: © 2013 Soni RK, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.12/2013;
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ABSTRACT: The activation-induced deaminase (AID)/APOBEC cytidine deaminases participate in a diversity of biological processes from the regulation of protein expression to embryonic development and host defenses. In its classical role, AID mutates germline-encoded sequences of B cell receptors, a key aspect of adaptive immunity, and APOBEC1, mutates apoprotein B pre-mRNA, yielding two isoforms important for cellular function and plasma lipid metabolism. Investigations over the last ten years have uncovered a role of the APOBEC superfamily in intrinsic immunity against viruses and innate immunity against viral infection by deamination and mutation of viral genomes. Further, discovery in the area of human immunodeficiency virus (HIV) infection revealed that the HIV viral infectivity factor protein interacts with APOBEC3G, targeting it for proteosomal degradation, overriding its antiviral function. More recently, our and others' work have uncovered that the AID and APOBEC cytidine deaminase family members have an even more direct link between activity against viral infection and induction and shaping of adaptive immunity than previously thought, including that of antigen processing for cytotoxic T lymphocyte activity and natural killer cell activation. Newly ascribed functions of these cytodine deaminases will be discussed, including their newly identified roles in adaptive immunity, epigenetic regulation, and cell differentiation. Herein this review we discuss AID and APOBEC cytodine deaminases as a link between innate and adaptive immunity uncovered by recent studies.Frontiers in Microbiology 10/2014; 5:534. · 3.94 Impact Factor