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Cell Aug 1983
Review
Topics: Alpharetrovirus; Animals; Avian Leukosis Virus; Cell Differentiation; Cell Membrane; Cell Transformation, Neoplastic; Cell Transformation, Viral; Chickens; Cytoplasm; Erythroblasts; Erythrocytes; Erythropoiesis; Genes, Viral; Hematopoietic Stem Cells; Mutation; Oncogenes; Viral Proteins
PubMed: 6309413
DOI: 10.1016/0092-8674(83)90130-7 -
Journal of Virology Jul 2010Accidental insertional activation of proto-oncogenes and potential vector mobilization pose serious challenges for human gene therapy using retroviral vectors....
Accidental insertional activation of proto-oncogenes and potential vector mobilization pose serious challenges for human gene therapy using retroviral vectors. Comparative analyses of integration sites of different retroviral vectors have elucidated distinct target site preferences, highlighting vectors based on the alpharetrovirus Rous sarcoma virus (RSV) as those with the most neutral integration spectrum. To date, alpharetroviral vector systems are based mainly on single constructs containing viral coding sequences and intact long terminal repeats (LTR). Even though they are considered to be replication incompetent in mammalian cells, the transfer of intact viral genomes is unacceptable for clinical applications, due to the risk of vector mobilization and the potentially immunogenic expression of viral proteins, which we minimized by setting up a split-packaging system expressing the necessary viral proteins in trans. Moreover, intact LTRs containing transcriptional elements are capable of activating cellular genes. By removing most of these transcriptional elements, we were able to generate a self-inactivating (SIN) alpharetroviral vector, whose LTR transcriptional activity is strongly reduced and whose transgene expression can be driven by an internal promoter of choice. Codon optimization of the alpharetroviral Gag/Pol expression construct and further optimization steps allowed the production of high-titer self-inactivating vector particles in human cells. We demonstrate proof of principle for the versatility of alpharetroviral SIN vectors for the genetic modification of murine and human hematopoietic cells at a low multiplicity of infection.
Topics: Alpharetrovirus; Animals; Cell Line; Cells, Cultured; Gene Expression; Genetic Therapy; Genetic Vectors; Humans; Mice; Promoter Regions, Genetic; RNA, Viral; Terminal Repeat Sequences; Transgenes; Virus Assembly
PubMed: 20410274
DOI: 10.1128/JVI.00182-10 -
Viruses Jan 2021The assembly of a hexameric lattice of retroviral immature particles requires the involvement of cell factors such as proteins and small molecules. A small, negatively...
The assembly of a hexameric lattice of retroviral immature particles requires the involvement of cell factors such as proteins and small molecules. A small, negatively charged polyanionic molecule, myo-inositol hexaphosphate (IP6), was identified to stimulate the assembly of immature particles of HIV-1 and other lentiviruses. Interestingly, cryo-electron tomography analysis of the immature particles of two lentiviruses, HIV-1 and equine infectious anemia virus (EIAV), revealed that the IP6 binding site is similar. Based on this amino acid conservation of the IP6 interacting site, it is presumed that the assembly of immature particles of all lentiviruses is stimulated by IP6. Although this specific region for IP6 binding may be unique for lentiviruses, it is plausible that other retroviral species also recruit some small polyanion to facilitate the assembly of their immature particles. To study whether the assembly of retroviruses other than lentiviruses can be stimulated by polyanionic molecules, we measured the effect of various polyanions on the assembly of immature virus-like particles of Rous sarcoma virus (RSV), a member of alpharetroviruses, Mason-Pfizer monkey virus (M-PMV) representative of betaretroviruses, and murine leukemia virus (MLV), a member of gammaretroviruses. RSV, M-PMV and MLV immature virus-like particles were assembled in vitro from truncated Gag molecules and the effect of selected polyanions, myo-inostol hexaphosphate, myo-inositol, glucose-1,6-bisphosphate, myo-inositol hexasulphate, and mellitic acid, on the particles assembly was quantified. Our results suggest that the assembly of immature particles of RSV and MLV was indeed stimulated by the presence of myo-inostol hexaphosphate and myo-inositol, respectively. In contrast, no effect on the assembly of M-PMV as a betaretrovirus member was observed.
Topics: Alpharetrovirus; Animals; Betaretrovirus; Cell Membrane; Cells, Cultured; Gammaretrovirus; Gene Products, gag; Host-Pathogen Interactions; Polyelectrolytes; Retroviridae; Virion; Virus Assembly
PubMed: 33477490
DOI: 10.3390/v13010129 -
Cancer Detection and Prevention 1994Viruses of the avian leukosis/sarcoma group (ALSV) and reticuloendotheliosis viruses (REV) are highly prevalent in chickens and turkeys and naturally cause tumors in... (Review)
Review
Viruses of the avian leukosis/sarcoma group (ALSV) and reticuloendotheliosis viruses (REV) are highly prevalent in chickens and turkeys and naturally cause tumors in them. Commercial chickens are positive for antibodies, and a proportion actually carry infectious virus. Virus may be present in chicken products and in eggs, thus human exposure is virtually universal. The viruses show little potential for producing infectious viral particles in mammalian cells; nevertheless, they have the capacity to infect and transform mammalian cells (including human cells) in vitro, and to induce tumors in a variety of mammals, including primates. Most, but not all, of the serological studies in humans have been negative. Given the known behavior of these viruses in mammals, this was not unexpected. Moreover, there were methodological problems with most of the studies. There is some epidemiological evidence associating putative poultry exposure with cancer in humans. However, this has not been rigorously investigated. This paper is a comprehensive review of the extent of the carcinogenic potential these viruses show for humans. It is concluded, virological evidence indicates, that these viruses could conceivably have a carcinogenic potential for humans, but if so, at a level much less than in chickens. Whether this is insignificant, or translates to a real risk, is not known at the moment. Therefore, there is a need for definitive studies to completely rule out this possibility.
Topics: Alpharetrovirus; Animals; Antibodies, Viral; Cell Transformation, Viral; Humans; Neoplasms; Oncogenes; Reticuloendotheliosis virus
PubMed: 8162609
DOI: No ID Found -
Journal of Virology Jul 2000Current models of retroviral entry hypothesize that interactions between the host cell receptor(s) and viral envelope protein induce structural changes in the envelope...
Current models of retroviral entry hypothesize that interactions between the host cell receptor(s) and viral envelope protein induce structural changes in the envelope protein that convert it to an active conformation, allowing it to mediate fusion with the membrane. Recent evidence supporting this hypothesis is the demonstration that Tva, the receptor for subgroup A avian sarcoma and leukosis virus (ASLV-A), induces conformational changes in the viral envelope protein. These changes include conversion of the envelope protein to an active, membrane-binding state likely representing a fusogenic conformation. To determine whether binding of the soluble Tva (sTva) receptor was sufficient to activate fully the fusogenic potential of the ASLV-A envelope protein, we have evaluated the ability of ASLV-A to infect receptor-deficient cell lines in the presence of sTva. Soluble receptor efficiently mediated infection of cells devoid of endogenous Tva in a dose-dependent manner, and this infection was dependent absolutely on the addition of sTva. The infectivity of the virus was enhanced dramatically in the presence of the polycationic polymer Polybrene or when centrifugal forces were applied during inoculation, resulting in viral titers comparable to those achieved on cells expressing endogenous receptor. sTva functioned to mediate infection at low concentrations, approaching the estimated binding constant of the receptor and viral envelope protein. These results demonstrate that receptor binding can activate the ASLV-A envelope protein and convert it to a fusogenic conformation competent to mediate the fusion of the viral and cellular membranes.
Topics: Alpharetrovirus; Avian Proteins; Cell Line; Gene Products, env; Hexadimethrine Bromide; Humans; Protein Binding; Receptors, Virus; Solubility
PubMed: 10864659
DOI: 10.1128/jvi.74.14.6469-6475.2000 -
Scientific Reports Jan 2015The viral cell receptors and infection can be blocked by the expression of the viral receptor-binding protein. Thus, the viral cell receptor is an attractive target for...
The viral cell receptors and infection can be blocked by the expression of the viral receptor-binding protein. Thus, the viral cell receptor is an attractive target for anti-viral strategies, and the identification of viral cell receptor is critical for better understanding and controlling viral disease. As a model system for viral entry and anti-retroviral approaches, avian sarcoma/leukosis virus (ASLV, including the A-J ten subgroups) has been studied intensively and many milestone discoveries have been achieved based on work with ASLV. Here, we used a DF1 cell line expressed viral receptor-binding protein to efficiently identify chicken Annexin A2 (chANXA2) as a novel receptor for retrovirus ALV-J (avian leukosis virus subgroup J). Our data demonstrate that antibodies or siRNA to chANXA2 significantly inhibited ALV-J infection and replication, and over-expression of chANXA2 permitted the entry of ALV-J into its non-permissible cells. Our findings have not only identified chANXA2 as a novel biomarker for anti-ALV-J, but also demonstrated that cell lines with the expression of viral receptor-binding protein could be as efficient tools for isolating functional receptors to identify novel anti-viral targets.
Topics: Alpharetrovirus; Animals; Annexin A2; Avian Proteins; Chickens; HEK293 Cells; Humans; Receptors, Virus
PubMed: 25604889
DOI: 10.1038/srep07935 -
Virology Sep 1969
Topics: Alpharetrovirus; Animals; Antigens; Avian Leukosis Virus; Avian Sarcoma Viruses; Birds; Cell Line; Chick Embryo; Chickens; Cricetinae; Ducks; Fibroblasts; Immune Sera; Neutralization Tests; Satellite Viruses; Viral Interference
PubMed: 4309068
DOI: 10.1016/0042-6822(69)90344-4 -
Experimental Cell Research Jul 1977
Topics: Alpharetrovirus; Animals; Avian Leukosis Virus; Cell Division; Cell Survival; Cell Transformation, Neoplastic; Chick Embryo; Clone Cells; Culture Media; Fibroblasts; Mutation; Temperature
PubMed: 194785
DOI: 10.1016/0014-4827(77)90363-9 -
Virology Dec 1969
Topics: Alpharetrovirus; Animals; Cell Line; Chick Embryo; Fibroblasts; Mutation; Temperature
PubMed: 4311641
DOI: 10.1016/0042-6822(69)90030-0 -
Folia Biologica 1995Although there are substantial differences between retroviruses originating from avian and primate species, a comparison of these two different biological systems... (Review)
Review
Although there are substantial differences between retroviruses originating from avian and primate species, a comparison of these two different biological systems reveals that interaction of these retroviruses with heterologous hosts involves similar biological principles. Retroviral isolates with high replicative capacity in natural targets (e.g. CD4+ lymphocytes and macrophages for human immunodeficiency viruses (HIVs) can infect other cell types [e.g. CD- astrocytes, follicular dendritic cells (FDC) in vivo and/or CD4+ neoplastic T cells in vitro] as well. These viral isolates may have a potential of infecting heterologous cells in vitro and can enlarge their host-range by establishing infection in other species, distantly related. Strains of avian sarcoma/leukemia viruses (ASLV) originating from their natural hosts, chickens, and infectious for other avian species, ducks, can frequently infect mammals (rodents). Similarly, HIV-1 strains infectious for chimpanzees possess capacity of establishing chronic infection in pig-tailed macaques. The broad host-range of retroviral isolates in both viral systems is accompanied by presence of additional structures in viral envelope. These novel or additional envelope structures may recognize alternate viral receptor(s). Moreover, the enlarged host range of primary HIV-1 isolates is evaluated by infection of neoplastic CD4+ permanent cell line, MT2, and serves as a predictive marker of progression of the viral infection toward AIDS.
Topics: Alpharetrovirus; Animals; CD4-Positive T-Lymphocytes; Chickens; HIV; Humans; Mice
PubMed: 7621964
DOI: No ID Found