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Clinical and Vaccine Immunology : CVI Jun 2015The cheetah population in Namibia is the largest free-ranging population in the world and a key population for research regarding the health status of this species. We...
The cheetah population in Namibia is the largest free-ranging population in the world and a key population for research regarding the health status of this species. We used serological methods and quantitative real-time PCR to test free-ranging and captive Namibian cheetahs for the presence of feline leukemia virus (FeLV), a gammaretrovirus that can be highly aggressive in populations with low genetic diversity, such as cheetahs. We also assessed the presence of antibodies to other gammaretroviruses and the responses to a FeLV vaccine developed for domestic cats. Up to 19% of the free-ranging cheetahs, 27% of the captive nonvaccinated cheetahs, and 86% of the captive vaccinated cheetahs tested positive for FeLV antibodies. FeLV-antibody-positive free-ranging cheetahs also tested positive for Rauscher murine leukemia virus antibodies. Nevertheless, FeLV was not detectable by quantitative real-time PCR and no reverse transcriptase activity was detectable by product-enhanced reverse transcriptase assay in the plasma of cheetahs or the supernatants from cultures of peripheral blood mononuclear cells. The presence of antibodies to gammaretroviruses in clinically healthy specimens may be caused either by infection with a low-pathogenic retrovirus or by the expression of endogenous retroviral sequences. The strong humoral immune responses to FeLV vaccination demonstrate that cheetahs can respond to the vaccine and that vaccination against FeLV infection may be beneficial should FeLV infection ever become a threat, as was seen in Iberian lynx and Florida panthers.
Topics: Acinonyx; Animals; Antibodies, Viral; Blood; Leukemia Virus, Feline; Male; Namibia; Real-Time Polymerase Chain Reaction; Retrospective Studies; Retroviridae Infections; Serologic Tests; Tumor Virus Infections; Viral Vaccines
PubMed: 25809630
DOI: 10.1128/CVI.00705-14 -
Molecular Therapy : the Journal of the... May 2017β-Thalassemia and sickle cell disease (SCD) are the world's two most widely disseminated hereditary hemoglobinopathies. β-Thalassemia originated in the Mediterranean,... (Review)
Review
β-Thalassemia and sickle cell disease (SCD) are the world's two most widely disseminated hereditary hemoglobinopathies. β-Thalassemia originated in the Mediterranean, Middle Eastern, and Asian regions, and SCD originated in central Africa. However, subsequent population migration means that these two diseases are now global and thus constitute a growing health problem in many countries. Despite remarkable improvements in medical care for patients with β-hemoglobinopathies, there is still only one definitive treatment option: allogeneic hematopoietic stem cell (HSC) transplantation. The development of gene therapy for β-hemoglobinopathies has been justified by (1) the limited availability of human leukocyte antigen (HLA)-identical donors, (2) the narrow window of application of HSC transplantation to the youngest patients, and (3) recent advances in HSC-based gene therapy. The huge ongoing efforts in translational medicine and the high number of related publications show that gene therapy has the potential to become the treatment of choice for patients who lack either an HLA genoidentical sibling or an alternative, medically acceptable donor. In this dynamic scientific context, we first summarize the main steps toward clinical translation of this therapeutic approach and then discuss novel lentiviral- and genome editing-based treatment strategies for β-hemoglobinopathies.
Topics: Anemia, Sickle Cell; Gammaretrovirus; Gene Editing; Gene Expression; Genetic Therapy; Genetic Vectors; HLA Antigens; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells; Humans; Lentivirus; Mutation; Tissue Donors; Transplantation, Homologous; beta-Globins; beta-Thalassemia
PubMed: 28377044
DOI: 10.1016/j.ymthe.2017.03.024 -
Viruses Oct 2021Porcine endogenous retroviruses (PERVs) are integrated in the genome of all pigs, and some of them are able to infect human cells. Therefore, PERVs pose a risk for... (Review)
Review
Porcine endogenous retroviruses (PERVs) are integrated in the genome of all pigs, and some of them are able to infect human cells. Therefore, PERVs pose a risk for xenotransplantation, the transplantation of pig cells, tissues, or organ to humans in order to alleviate the shortage of human donor organs. Up to 2021, a huge body of knowledge about PERVs has been accumulated regarding their biology, including replication, recombination, origin, host range, and immunosuppressive properties. Until now, no PERV transmission has been observed in clinical trials transplanting pig islet cells into diabetic humans, in preclinical trials transplanting pig cells and organs into nonhuman primates with remarkable long survival times of the transplant, and in infection experiments with several animal species. Nevertheless, in order to prevent virus transmission to the recipient, numerous strategies have been developed, including selection of PERV-C-free animals, RNA interference, antiviral drugs, vaccination, and genome editing. Furthermore, at present there are no more experimental approaches to evaluate the full risk until we move to the clinic.
Topics: Animals; Endogenous Retroviruses; Gammaretrovirus; Host Specificity; Immunosuppressive Agents; Retroviridae Infections; Swine; Swine Diseases; Transplantation, Heterologous; Zoonoses
PubMed: 34834962
DOI: 10.3390/v13112156 -
Molecular Therapy : the Journal of the... May 2017Prior to the first successful bone marrow transplant in 1968, patients born with severe combined immunodeficiency (SCID) invariably died. Today, with a widening... (Review)
Review
Prior to the first successful bone marrow transplant in 1968, patients born with severe combined immunodeficiency (SCID) invariably died. Today, with a widening availability of newborn screening, major improvements in the application of allogeneic procedures, and the emergence of successful hematopoietic stem and progenitor cell (HSC/P) gene therapy, the majority of these children can be identified and cured. Here, we trace key steps in the development of clinical gene therapy for SCID and other primary immunodeficiencies (PIDs), and review the prospects for adoption of new targets and technologies.
Topics: Adenosine Deaminase; Clinical Trials as Topic; Gammaretrovirus; Gene Expression; Genetic Therapy; Genetic Vectors; Hematopoietic Stem Cell Transplantation; History, 20th Century; History, 21st Century; Humans; Immunologic Deficiency Syndromes; Lentivirus; Severe Combined Immunodeficiency; Transplantation, Homologous
PubMed: 28366768
DOI: 10.1016/j.ymthe.2017.03.018 -
Viruses Jan 2023After the onset of the AIDS pandemic, HIV-1 (genus ) became the predominant model for studying retrovirus Env glycoproteins and their role in entry. However, HIV Env is... (Review)
Review
After the onset of the AIDS pandemic, HIV-1 (genus ) became the predominant model for studying retrovirus Env glycoproteins and their role in entry. However, HIV Env is an inadequate model for understanding entry of viruses in the , and genera. For example, oncogenic model system viruses such as Rous sarcoma virus (RSV, ), murine leukemia virus (MLV, ) and human T-cell leukemia viruses (HTLV-I and HTLV-II, ) encode Envs that are structurally and functionally distinct from HIV Env. We refer to these as Gamma-type Envs. Gamma-type Envs are probably the most widespread retroviral Envs in nature. They are found in exogenous and endogenous retroviruses representing a broad spectrum of vertebrate hosts including amphibians, birds, reptiles, mammals and fish. In endogenous form, gamma-type Envs have been evolutionarily coopted numerous times, most notably as placental syncytins (e.g., human SYNC1 and SYNC2). Remarkably, gamma-type Envs are also found outside of the . Gp2 proteins of filoviruses (e.g., Ebolavirus) and snake arenaviruses in the genus are gamma-type Env homologs, products of ancient recombination events involving viruses of different Baltimore classes. Distinctive hallmarks of gamma-type Envs include a labile disulfide bond linking the surface and transmembrane subunits, a multi-stage attachment and fusion mechanism, a highly conserved (but poorly understood) "immunosuppressive domain", and activation by the viral protease during virion maturation. Here, we synthesize work from diverse retrovirus model systems to illustrate these distinctive properties and to highlight avenues for further exploration of gamma-type Env structure and function.
Topics: Female; Pregnancy; Animals; Humans; Mice; Placenta; Gammaretrovirus; Alpharetrovirus; Leukemia Virus, Murine; Ebolavirus; Endogenous Retroviruses; HIV Seropositivity; Glycoproteins; Mammals
PubMed: 36851488
DOI: 10.3390/v15020274 -
Journal of Virology Apr 2023High-throughput sequences were generated from DNA and cDNA from four Southern white rhinoceros () located in the Taronga Western Plain Zoo in Australia. Virome analysis...
High-throughput sequences were generated from DNA and cDNA from four Southern white rhinoceros () located in the Taronga Western Plain Zoo in Australia. Virome analysis identified reads that were similar to endogenous gammaretrovirus (McERV). Previous analysis of perissodactyl genomes did not recover gammaretroviruses. Our analysis, including the screening of the updated white rhinoceros () and black rhinoceros () draft genomes identified high-copy orthologous gammaretroviral ERVs. Screening of Asian rhinoceros, extinct rhinoceros, domestic horse, and tapir genomes did not identify related gammaretroviral sequences in these species. The newly identified proviral sequences were designated SimumERV and DicerosERV for the white and black rhinoceros retroviruses, respectively. Two long terminal repeat (LTR) variants (LTR-A and LTR-B) were identified in the black rhinoceros, with different copy numbers associated with each ( = 101 and 373, respectively). Only the LTR-A lineage ( = 467) was found in the white rhinoceros. The African and Asian rhinoceros lineages diverged approximately 16 million years ago. Divergence age estimation of the identified proviruses suggests that the exogenous retroviral ancestor of the African rhinoceros ERVs colonized their genomes within the last 8 million years, a result consistent with the absence of these gammaretroviruses from Asian rhinoceros and other perissodactyls. The black rhinoceros germ line was colonized by two lineages of closely related retroviruses and white rhinoceros by one. Phylogenetic analysis indicates a close evolutionary relationship with ERVs of rodents including sympatric African rats, suggesting a possible African origin of the identified rhinoceros gammaretroviruses. Rhinoceros genomes were thought to be devoid of gammaretroviruses, as has been determined for other perissodactyls (horses, tapirs, and rhinoceros). While this may be true of most rhinoceros, the African white and black rhinoceros genomes have been colonized by evolutionarily young gammaretroviruses (SimumERV and DicerosERV for the white and black rhinoceros, respectively). These high-copy endogenous retroviruses (ERVs) may have expanded in multiple waves. The closest relative of SimumERV and DicerosERV is found in rodents, including African endemic species. Restriction of the ERVs to African rhinoceros suggests an African origin for the rhinoceros gammaretroviruses.
Topics: Animals; Mice; Rats; Biological Evolution; Endogenous Retroviruses; Gammaretrovirus; Horses; Perissodactyla; Phylogeny; Proviruses
PubMed: 37022231
DOI: 10.1128/jvi.01932-22 -
Microbiology and Molecular Biology... Mar 2018Viruses of the subfamily are defined by the ability to reverse transcribe an RNA genome into DNA that integrates into the host cell genome during the intracellular... (Review)
Review
Viruses of the subfamily are defined by the ability to reverse transcribe an RNA genome into DNA that integrates into the host cell genome during the intracellular virus life cycle. Exogenous retroviruses (XRVs) are horizontally transmitted between host individuals, with disease outcome depending on interactions between the retrovirus and the host organism. When retroviruses infect germ line cells of the host, they may become endogenous retroviruses (ERVs), which are permanent elements in the host germ line that are subject to vertical transmission. These ERVs sometimes remain infectious and can themselves give rise to XRVs. This review integrates recent developments in the phylogenetic classification of retroviruses and the identification of retroviral receptors to elucidate the origins and evolution of XRVs and ERVs. We consider whether ERVs may recurrently pressure XRVs to shift receptor usage to sidestep ERV interference. We discuss how related retroviruses undergo alternative fates in different host lineages after endogenization, with koala retrovirus (KoRV) receiving notable interest as a recent invader of its host germ line. KoRV is heritable but also infectious, which provides insights into the early stages of germ line invasions as well as XRV generation from ERVs. The relationship of KoRV to primate and other retroviruses is placed in the context of host biogeography and the potential role of bats and rodents as vectors for interspecies viral transmission. Combining studies of extant XRVs and "fossil" endogenous retroviruses in koalas and other Australasian species has broadened our understanding of the evolution of retroviruses and host-retrovirus interactions.
Topics: Animals; Disease Reservoirs; Endogenous Retroviruses; Evolution, Molecular; Gammaretrovirus; Host-Pathogen Interactions; Humans; Mice; Phascolarctidae; Phylogeny; Phylogeography; Rats; Retroviridae Infections; Tumor Virus Infections; Zoonoses
PubMed: 29237726
DOI: 10.1128/MMBR.00044-17 -
Viruses Dec 2014The mouse gammaretroviruses associated with leukemogenesis are found in the classical inbred mouse strains and in house mouse subspecies as infectious exogenous viruses... (Review)
Review
The mouse gammaretroviruses associated with leukemogenesis are found in the classical inbred mouse strains and in house mouse subspecies as infectious exogenous viruses (XRVs) and as endogenous retroviruses (ERVs) inserted into their host genomes. There are three major mouse leukemia virus (MuLV) subgroups in laboratory mice: ecotropic, xenotropic, and polytropic. These MuLV subgroups differ in host range, pathogenicity, receptor usage and subspecies of origin. The MuLV ERVs are recent acquisitions in the mouse genome as demonstrated by the presence of many full-length nondefective MuLV ERVs that produce XRVs, the segregation of these MuLV subgroups into different house mouse subspecies, and by the positional polymorphism of these loci among inbred strains and individual wild mice. While some ecotropic and xenotropic ERVs can produce XRVs directly, others, especially the pathogenic polytropic ERVs, do so only after recombinations that can involve all three ERV subgroups. Here, I describe individual MuLV ERVs found in the laboratory mice, their origins and geographic distribution in wild mouse subspecies, their varying ability to produce infectious virus and the biological consequences of this expression.
Topics: Animals; Endogenous Retroviruses; Evolution, Molecular; Leukemia Virus, Murine; Mice; Topography, Medical
PubMed: 25549291
DOI: 10.3390/v7010001 -
Viruses Jun 2011Retroviruses are evolutionary optimized gene carriers that have naturally adapted to their hosts to efficiently deliver their nucleic acids into the target cell... (Review)
Review
Retroviruses are evolutionary optimized gene carriers that have naturally adapted to their hosts to efficiently deliver their nucleic acids into the target cell chromatin, thereby overcoming natural cellular barriers. Here we will review-starting with a deeper look into retroviral biology-how Murine Leukemia Virus (MLV), a simple gammaretrovirus, can be converted into an efficient vehicle of genetic therapeutics. Furthermore, we will describe how more rational vector backbones can be designed and how these so-called self-inactivating vectors can be pseudotyped and produced. Finally, we will provide an overview on existing clinical trials and how biosafety can be improved.
Topics: Animals; Genetic Therapy; Genetic Vectors; Humans; Leukemia Virus, Murine
PubMed: 21994751
DOI: 10.3390/v3060677 -
Clinical and Translational Science Jul 2017
Review
Topics: Adenoviridae; CRISPR-Cas Systems; Drug Approval; Gammaretrovirus; Gene Editing; Genetic Therapy; Genetic Vectors; Humans; Lentivirus; Oncolytic Viruses; RNA Interference
PubMed: 28383804
DOI: 10.1111/cts.12466