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Viruses Sep 2011With constantly changing environmental selection pressures, retroviruses rely upon recombination to reassort polymorphisms in their genomes and increase genetic... (Review)
Review
With constantly changing environmental selection pressures, retroviruses rely upon recombination to reassort polymorphisms in their genomes and increase genetic diversity, which improves the chances for the survival of their population. Recombination occurs during DNA synthesis, whereby reverse transcriptase undergoes template switching events between the two copackaged RNAs, resulting in a viral recombinant with portions of the genetic information from each parental RNA. This review summarizes our current understanding of the factors and mechanisms influencing retroviral recombination, fidelity of the recombination process, and evaluates the subsequent viral diversity and fitness of the progeny recombinant. Specifically, the high mutation rates and high recombination frequencies of HIV-1 will be analyzed for their roles in influencing HIV-1 global diversity, as well as HIV-1 diagnosis, drug treatment, and vaccine development.
Topics: DNA Replication; DNA, Viral; Genetic Variation; Genome, Viral; HIV Infections; HIV-1; Humans; Mutation Rate; RNA, Viral; Recombination, Genetic; Retroviridae; Virus Replication
PubMed: 21994801
DOI: 10.3390/v3091650 -
Retrovirology Oct 2006When endogenous retroviruses (ERV) were discovered in the late 1960s, the Mendelian inheritance of retroviral genomes by their hosts was an entirely new concept. Indeed... (Review)
Review
When endogenous retroviruses (ERV) were discovered in the late 1960s, the Mendelian inheritance of retroviral genomes by their hosts was an entirely new concept. Indeed Howard M Temin's DNA provirus hypothesis enunciated in 1964 was not generally accepted, and reverse transcriptase was yet to be discovered. Nonetheless, the evidence that we accrued in the pre-molecular era has stood the test of time, and our hypothesis on ERV, which one reviewer described as 'impossible', proved to be correct. Here I recount some of the key observations in birds and mammals that led to the discovery of ERV, and comment on their evolution, cross-species dispersion, and what remains to be elucidated.
Topics: Animals; Endogenous Retroviruses; Evolution, Molecular; History, 20th Century; Humans; Mammals; Mice; Phylogeny; Proviruses; Retroviridae; Virology
PubMed: 17018135
DOI: 10.1186/1742-4690-3-67 -
Genome Biology and Evolution Jan 2023Koala populations show marked differences in inbreeding levels and in the presence or absence of the endogenous Koala retrovirus (KoRV). These genetic differences among...
Koala populations show marked differences in inbreeding levels and in the presence or absence of the endogenous Koala retrovirus (KoRV). These genetic differences among populations may lead to severe disease impacts threatening koala population viability. In addition, the recent colonization of the koala genome by KoRV provides a unique opportunity to study the process of retroviral adaptation to vertebrate genomes and the impact this has on speciation, genome structure, and function. The genome build described here is from an animal from the bottlenecked Southern population free of endogenous and exogenous KoRV. It provides a more contiguous genome build than the previous koala reference derived from an animal from a more outbred Northern population and is the first koala genome from a KoRV polymerase-free animal.
Topics: Animals; Phascolarctidae; Australia; Retroviridae Infections; Retroviridae; Gammaretrovirus; Endogenous Retroviruses
PubMed: 36542479
DOI: 10.1093/gbe/evac176 -
Viruses Apr 2024The field of retroviral integration research has a long history that started with the provirus hypothesis and subsequent discoveries of the retroviral reverse... (Review)
Review
The field of retroviral integration research has a long history that started with the provirus hypothesis and subsequent discoveries of the retroviral reverse transcriptase and integrase enzymes. Because both enzymes are essential for retroviral replication, they became valued targets in the effort to discover effective compounds to inhibit HIV-1 replication. In 2007, the first integrase strand transfer inhibitor was licensed for clinical use, and subsequently approved second-generation integrase inhibitors are now commonly co-formulated with reverse transcriptase inhibitors to treat people living with HIV. International meetings specifically focused on integrase and retroviral integration research first convened in 1995, and this paper is part of the Special Issue on the 7th International Conference on Retroviral Integration, which was held in Boulder Colorado in the summer of 2023. Herein, we overview key historical developments in the field, especially as they pertain to the development of the strand transfer inhibitor drug class. Starting from the mid-1990s, research advancements are presented through the lens of the international conferences. Our overview highlights the impact that regularly scheduled, subject-specific international meetings can have on community-building and, as a result, on field-specific collaborations and scientific advancements.
Topics: Humans; Virus Integration; Retroviridae; Congresses as Topic; HIV Infections; HIV-1; History, 21st Century; History, 20th Century
PubMed: 38675945
DOI: 10.3390/v16040604 -
Viruses Dec 2022To complete their replication cycle, retroviruses need to integrate a DNA copy of their RNA genome into a host chromosome. Integration site selection is not random and... (Review)
Review
To complete their replication cycle, retroviruses need to integrate a DNA copy of their RNA genome into a host chromosome. Integration site selection is not random and is driven by multiple viral and cellular host factors specific to different classes of retroviruses. Today, overwhelming evidence from cell culture, animal experiments and clinical data suggests that integration sites are important for retroviral replication, oncogenesis and/or latency. In this review, we will summarize the increasing knowledge of the mechanisms underlying the integration site selection of the gammaretrovirus MLV and the lentivirus HIV-1. We will discuss how host factors of the integration site selection of retroviruses may steer the development of safer viral vectors for gene therapy. Next, we will discuss how altering the integration site preference of HIV-1 using small molecules could lead to a cure for HIV-1 infection.
Topics: Animals; HIV-1; Virus Integration; Retroviridae; Lentivirus; HIV Infections; Genetic Vectors
PubMed: 36680071
DOI: 10.3390/v15010032 -
Retrovirology May 2004During the last two decades, the profusion of HIV research due to the urge to identify new therapeutic targets has led to a wealth of information on the retroviral... (Review)
Review
During the last two decades, the profusion of HIV research due to the urge to identify new therapeutic targets has led to a wealth of information on the retroviral replication cycle. However, while the late stages of the retrovirus life cycle, consisting of virus replication and egress, have been partly unraveled, the early steps remain largely enigmatic. These early steps consist of a long and perilous journey from the cell surface to the nucleus where the proviral DNA integrates into the host genome. Retroviral particles must bind specifically to their target cells, cross the plasma membrane, reverse-transcribe their RNA genome, while uncoating the cores, find their way to the nuclear membrane and penetrate into the nucleus to finally dock and integrate into the cellular genome. Along this journey, retroviruses hijack the cellular machinery, while at the same time counteracting cellular defenses. Elucidating these mechanisms and identifying which cellular factors are exploited by the retroviruses and which hinder their life cycle, will certainly lead to the discovery of new ways to inhibit viral replication and to improve retroviral vectors for gene transfer. Finally, as proven by many examples in the past, progresses in retrovirology will undoubtedly also provide some priceless insights into cell biology.
Topics: Animals; DNA, Viral; Genome, Viral; Humans; Life Cycle Stages; RNA, Viral; Retroviridae; Virus Integration; Virus Replication
PubMed: 15169567
DOI: 10.1186/1742-4690-1-9 -
Annual Review of Genetics 2008Retroviruses are highly successful intracellular parasites, and as such they are found in nearly all branches of life. Some are relatively benign, but many are highly... (Review)
Review
Retroviruses are highly successful intracellular parasites, and as such they are found in nearly all branches of life. Some are relatively benign, but many are highly pathogenic and can cause either acute or chronic diseases. Therefore, there is tremendous selective pressure on the host to prevent retroviral replication, and for this reason cells have evolved a variety of restriction factors that act to inhibit or block the viruses. This review is a survey of the best-characterized restriction factors capable of inhibiting retroviral replication and aims to highlight the diversity of strategies used for this task.
Topics: Animals; Antigens, CD; Cytidine Deaminase; GPI-Linked Proteins; Host-Pathogen Interactions; Humans; Membrane Glycoproteins; RNA, Viral; RNA-Binding Proteins; Retroviridae; Virus Replication; Zinc Fingers
PubMed: 18624631
DOI: 10.1146/annurev.genet.42.110807.091704 -
Current Issues in Molecular Biology Jan 2004Members of the Tc1/mariner superfamily of transposable elements isolated from vertebrate species are inactive due to the accumulation of mutations. A representative of a... (Review)
Review
Members of the Tc1/mariner superfamily of transposable elements isolated from vertebrate species are inactive due to the accumulation of mutations. A representative of a subfamily of fish elements estimated to be last active > 10 million years ago has been reconstructed, and named Sleeping Beauty(SB). This element opened up new avenues for studies on DNA transposition in vertebrates, and for the development of transposon tools for genetic manipulation in important model species and in humans. Multiple transposase binding sites within the terminal inverted repeats, a transpositional enhancer sequence, unequal affinity of the transposase to the binding sites and the activity of the cellular HMGB1 protein all contribute to a highly regulated assembly of SB synaptic complexes, which is likely a requirement for the subsequent catalytic steps. Host proteins involved in double-strand DNA break repair are limiting factors of SB transposition in mammalian cells, underscoring evolutionary, structural and functional links between DNA transposition, retroviral integration and V(D)J recombination. SB catalyzes efficient cut-and-paste transposition in a wide range of vertebrate cells in tissue culture, and in somatic tissues as well as the germline of the mouse and zebrafish in vivo, indicating its usefulness as a vector for transgenesis and insertional mutagenesis.
Topics: Animals; DNA Transposable Elements; Evolution, Molecular; Gene Transfer Techniques; HMGB1 Protein; Humans; Mutagenesis, Insertional; Nucleic Acid Conformation; Recombination, Genetic; Retroviridae
PubMed: 14632258
DOI: No ID Found -
Blood Feb 2012The genetic engineering of hematopoietic stem cells is the basis for potentially treating a large array of hereditary and acquired diseases, and stands as the paradigm... (Review)
Review
The genetic engineering of hematopoietic stem cells is the basis for potentially treating a large array of hereditary and acquired diseases, and stands as the paradigm for stem cell engineering in general. Recent clinical reports support the formidable promise of this approach but also highlight the limitations of the technologies used to date, which have on occasion resulted in clonal expansion, myelodysplasia, or leukemogenesis. New research directions, predicated on improved vector designs, targeted gene delivery or the therapeutic use of pluripotent stem cells, herald the advent of safer and more effective hematopoietic stem cell therapies that may transform medical practice. In this review, we place these recent advances in perspective, emphasizing the solutions emerging from a wave of new technologies and highlighting the challenges that lie ahead.
Topics: Cell Engineering; Gene Targeting; Gene Transfer Techniques; Genetic Engineering; Genetic Therapy; Genetic Vectors; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells; Humans; Models, Biological; Retroviridae
PubMed: 22096239
DOI: 10.1182/blood-2011-09-349993 -
BioMed Research International 2013Gene delivery vectors based on retroviral or lentiviral particles are considered powerful tools for biomedicine and biotechnology applications. Such vectors require... (Review)
Review
Gene delivery vectors based on retroviral or lentiviral particles are considered powerful tools for biomedicine and biotechnology applications. Such vectors require modification at the genomic level in the form of rearrangements to allow introduction of desired genes and regulatory elements (genotypic modification) as well as engineering of the physical virus particle (phenotypic modification) in order to mediate efficient and safe delivery of the genetic information to the target cell nucleus. Phenotypic modifications are typically introduced at the genomic level through genetic manipulation of the virus producing cells. However, this paper focuses on methods which allow modification of viral particle surfaces after they have exited the cell, that is, directly on the viral particles in suspension. These methods fall into three categories: (i) direct covalent chemical modification, (ii) membrane-topic reagents, and (iii) adaptor systems. Current applications of such techniques will be introduced and their advantages and disadvantages will be discussed.
Topics: Genetic Engineering; Genetic Vectors; Lentivirus; Retroviridae; Surface Properties; Virion
PubMed: 23691494
DOI: 10.1155/2013/253521