The Experts below are selected from a list of 201 Experts worldwide ranked by ideXlab platform
Masao Matsuoka - One of the best experts on this subject based on the ideXlab platform.
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preferential selection of human t cell leukemia virus type 1 provirus lacking the 5 long terminal repeat during oncogenesis
Journal of Virology, 2007Co-Authors: Maki Miyazaki, Jun-ichirou Yasunaga, Yuko Taniguchi, Sadahiro Tamiya, Tatsutoshi Nakahata, Masao MatsuokaAbstract:In adult T-cell leukemia (ATL) cells, a defective human T-cell leukemia virus type 1 (HTLV-1) provirus lacking the 5′ long terminal repeat (LTR), designated type 2 defective provirus, is frequently observed. To investigate the mechanism underlying the generation of the defective provirus, we sequenced HTLV-1 provirus integration sites from cases of ATL. In HTLV-1 Proviruses retaining both LTRs, 6-bp repeat sequences were adjacent to the 5′ and 3′ LTRs. In 8 of 12 cases with type 2 defective provirus, 6-bp repeats were identified at both ends. In five of these cases, a short repeat was bound to CA dinucleotides of the pol and env genes at the 5′ end, suggesting that these type 2 defective Proviruses were formed before integration. In four cases lacking the 6-bp repeat, short (6- to 26-bp) deletions in the host genome were identified, indicating that these defective Proviruses were generated after integration. Quantification indicated frequencies of type 2 defective provirus of less than 3.9% for two carriers, which are much lower than those seen for ATL cases (27.8%). In type 2 defective Proviruses, the second exons of the tax, rex, and p30 genes were frequently deleted, leaving Tax unable to activate NF-κB and CREB pathways. The HTLV-1 bZIP factor gene, located on the minus strand, is expressed in ATL cells with this defective provirus, and its coding sequences are intact, suggesting its significance in oncogenesis.
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Preferential Selection of Human T-Cell Leukemia Virus Type 1 Provirus Lacking the 5′ Long Terminal Repeat during Oncogenesis
Journal of Virology, 2007Co-Authors: Maki Miyazaki, Jun-ichirou Yasunaga, Yuko Taniguchi, Sadahiro Tamiya, Tatsutoshi Nakahata, Masao MatsuokaAbstract:In adult T-cell leukemia (ATL) cells, a defective human T-cell leukemia virus type 1 (HTLV-1) provirus lacking the 5′ long terminal repeat (LTR), designated type 2 defective provirus, is frequently observed. To investigate the mechanism underlying the generation of the defective provirus, we sequenced HTLV-1 provirus integration sites from cases of ATL. In HTLV-1 Proviruses retaining both LTRs, 6-bp repeat sequences were adjacent to the 5′ and 3′ LTRs. In 8 of 12 cases with type 2 defective provirus, 6-bp repeats were identified at both ends. In five of these cases, a short repeat was bound to CA dinucleotides of the pol and env genes at the 5′ end, suggesting that these type 2 defective Proviruses were formed before integration. In four cases lacking the 6-bp repeat, short (6- to 26-bp) deletions in the host genome were identified, indicating that these defective Proviruses were generated after integration. Quantification indicated frequencies of type 2 defective provirus of less than 3.9% for two carriers, which are much lower than those seen for ATL cases (27.8%). In type 2 defective Proviruses, the second exons of the tax, rex, and p30 genes were frequently deleted, leaving Tax unable to activate NF-κB and CREB pathways. The HTLV-1 bZIP factor gene, located on the minus strand, is expressed in ATL cells with this defective provirus, and its coding sequences are intact, suggesting its significance in oncogenesis.
Leonard H. Evans - One of the best experts on this subject based on the ideXlab platform.
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endogenous retroviruses mobilized during friend murine leukemia virus infection
Virology, 2016Co-Authors: Kyle Rosenke, Ethan J Hansen, Duncan Hendrick, Frank Malik, Leonard H. EvansAbstract:Abstract We have demonstrated in a mouse model that infection with a retrovirus can lead not only to the generation of recombinants between exogenous and endogenous gammaretrovirus, but also to the mobilization of endogenous Proviruses by pseudotyping entire polytropic proviral transcripts and facilitating their infectious spread to new cells. However, the frequency of this occurrence, the kinetics, and the identity of mobilized endogenous Proviruses was unclear. Here we find that these mobilized transcripts are detected after only one day of infection. They predominate over recombinant polytropic viruses early in infection, persist throughout the course of disease and are comprised of multiple different polytropic Proviruses. Other endogenous retroviral elements such as intracisternal A particles (IAPs) were not detected. The integration of the endogenous transcripts into new cells could result in loss of transcriptional control and elevated expression which may facilitate pathogenesis, perhaps by contributing to the generation of polytropic recombinant viruses.
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Precise Identification of Endogenous Proviruses of NFS/N Mice Participating in Recombination with Moloney Ecotropic Murine Leukemia Virus (MuLV) To Generate Polytropic MuLVs
Journal of virology, 2005Co-Authors: A. S. M. Alamgir, Frank Malik, Nick Owens, Marc Lavignon, Leonard H. EvansAbstract:Polytropic murine leukemia viruses (MuLVs) are generated by recombination of ecotropic MuLVs with env genes of a family of endogenous Proviruses in mice, resulting in viruses with an expanded host range and greater virulence. Inbred mouse strains contain numerous endogenous Proviruses that are potential donors of the env gene sequences of polytropic MuLVs; however, the precise identification of those Proviruses that participate in recombination has been elusive. Three different structural groups of Proviruses in NFS/N mice have been described and different ecotropic MuLVs preferentially recombine with different groups of Proviruses. In contrast to other ecotropic MuLVs such as Friend MuLV or Akv that recombine predominantly with a single group of Proviruses, Moloney MuLV (M-MuLV) recombines with at least two distinct groups. In this study, we determined that only three endogenous Proviruses, two of one group and one of another group, are major participants in recombination with M-MuLV. Furthermore, the distinction between the polytropic MuLVs generated by M-MuLV and other ecotropic MuLVs is the result of recombination with a single endogenous provirus. This provirus exhibits a frameshift mutation in the 3' region of the surface glycoprotein-encoding sequences that is excluded in recombinants with M-MuLV. The sites of recombination between the env genes of M-MuLV and endogenous Proviruses were confined to a short region exhibiting maximum homology between the ecotropic and polytropic env sequences and maximum stability of predicted RNA secondary structure. These observations suggest a possible mechanism for the specificity of recombination observed for different ecotropic MuLVs.
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precise identification of endogenous Proviruses of nfs n mice participating in recombination with moloney ecotropic murine leukemia virus mulv to generate polytropic mulvs
Journal of Virology, 2005Co-Authors: A. S. M. Alamgir, Frank Malik, Nick Owens, Marc Lavignon, Leonard H. EvansAbstract:Polytropic murine leukemia viruses (MuLVs) are generated by recombination of ecotropic MuLVs with env genes of a family of endogenous Proviruses in mice, resulting in viruses with an expanded host range and greater virulence. Inbred mouse strains contain numerous endogenous Proviruses that are potential donors of the env gene sequences of polytropic MuLVs; however, the precise identification of those Proviruses that participate in recombination has been elusive. Three different structural groups of Proviruses in NFS/N mice have been described and different ecotropic MuLVs preferentially recombine with different groups of Proviruses. In contrast to other ecotropic MuLVs such as Friend MuLV or Akv that recombine predominantly with a single group of Proviruses, Moloney MuLV (M-MuLV) recombines with at least two distinct groups. In this study, we determined that only three endogenous Proviruses, two of one group and one of another group, are major participants in recombination with M-MuLV. Furthermore, the distinction between the polytropic MuLVs generated by M-MuLV and other ecotropic MuLVs is the result of recombination with a single endogenous provirus. This provirus exhibits a frameshift mutation in the 3' region of the surface glycoprotein-encoding sequences that is excluded in recombinants with M-MuLV. The sites of recombination between the env genes of M-MuLV and endogenous Proviruses were confined to a short region exhibiting maximum homology between the ecotropic and polytropic env sequences and maximum stability of predicted RNA secondary structure. These observations suggest a possible mechanism for the specificity of recombination observed for different ecotropic MuLVs.
Robert F Siliciano - One of the best experts on this subject based on the ideXlab platform.
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replication competent noninduced Proviruses in the latent reservoir increase barrier to hiv 1 cure
Cell, 2013Co-Authors: Liang Shan, Nina N Hosmane, Jeffrey C Wang, Sarah B Laskey, Daniel I S Rosenbloom, Jun Lai, Joel N Blankson, Janet D Siliciano, Robert F SilicianoAbstract:Antiretroviral therapy fails to cure HIV-1 infection because latent Proviruses persist in resting CD4(+) T cells. T cell activation reverses latency, but <1% of Proviruses are induced to release infectious virus after maximum in vitro activation. The noninduced Proviruses are generally considered defective but have not been characterized. Analysis of 213 noninduced proviral clones from treated patients showed 88.3% with identifiable defects but 11.7% with intact genomes and normal long terminal repeat (LTR) function. Using direct sequencing and genome synthesis, we reconstructed full-length intact noninduced proviral clones and demonstrated growth kinetics comparable to reconstructed induced Proviruses from the same patients. Noninduced Proviruses have unmethylated promoters and are integrated into active transcription units. Thus, it cannot be excluded that they may become activated in vivo. The identification of replication-competent noninduced Proviruses indicates that the size of the latent reservoir-and, hence, the barrier to cure-may be up to 60-fold greater than previously estimated.
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analysis of human immunodeficiency virus type 1 viremia and provirus in resting cd4 t cells reveals a novel source of residual viremia in patients on antiretroviral therapy
Journal of Virology, 2009Co-Authors: Timothy P Brennan, Janet D Siliciano, Robert F Siliciano, John O Woods, Ahmad R Sedaghat, Claus O WilkeAbstract:Highly active antiretroviral therapy (HAART) can reduce human immunodeficiency virus type 1 (HIV-1) viremia to clinically undetectable levels. Despite this dramatic reduction, some virus is present in the blood. In addition, a long-lived latent reservoir for HIV-1 exists in resting memory CD4(+) T cells. This reservoir is believed to be a source of the residual viremia and is the focus of eradication efforts. Here, we use two measures of population structure--analysis of molecular variance and the Slatkin-Maddison test--to demonstrate that the residual viremia is genetically distinct from Proviruses in resting CD4(+) T cells but that Proviruses in resting and activated CD4(+) T cells belong to a single population. Residual viremia is genetically distinct from Proviruses in activated CD4(+) T cells, monocytes, and unfractionated peripheral blood mononuclear cells. The finding that some of the residual viremia in patients on HAART stems from an unidentified cellular source other than CD4(+) T cells has implications for eradication efforts.
Maki Miyazaki - One of the best experts on this subject based on the ideXlab platform.
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preferential selection of human t cell leukemia virus type 1 provirus lacking the 5 long terminal repeat during oncogenesis
Journal of Virology, 2007Co-Authors: Maki Miyazaki, Jun-ichirou Yasunaga, Yuko Taniguchi, Sadahiro Tamiya, Tatsutoshi Nakahata, Masao MatsuokaAbstract:In adult T-cell leukemia (ATL) cells, a defective human T-cell leukemia virus type 1 (HTLV-1) provirus lacking the 5′ long terminal repeat (LTR), designated type 2 defective provirus, is frequently observed. To investigate the mechanism underlying the generation of the defective provirus, we sequenced HTLV-1 provirus integration sites from cases of ATL. In HTLV-1 Proviruses retaining both LTRs, 6-bp repeat sequences were adjacent to the 5′ and 3′ LTRs. In 8 of 12 cases with type 2 defective provirus, 6-bp repeats were identified at both ends. In five of these cases, a short repeat was bound to CA dinucleotides of the pol and env genes at the 5′ end, suggesting that these type 2 defective Proviruses were formed before integration. In four cases lacking the 6-bp repeat, short (6- to 26-bp) deletions in the host genome were identified, indicating that these defective Proviruses were generated after integration. Quantification indicated frequencies of type 2 defective provirus of less than 3.9% for two carriers, which are much lower than those seen for ATL cases (27.8%). In type 2 defective Proviruses, the second exons of the tax, rex, and p30 genes were frequently deleted, leaving Tax unable to activate NF-κB and CREB pathways. The HTLV-1 bZIP factor gene, located on the minus strand, is expressed in ATL cells with this defective provirus, and its coding sequences are intact, suggesting its significance in oncogenesis.
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Preferential Selection of Human T-Cell Leukemia Virus Type 1 Provirus Lacking the 5′ Long Terminal Repeat during Oncogenesis
Journal of Virology, 2007Co-Authors: Maki Miyazaki, Jun-ichirou Yasunaga, Yuko Taniguchi, Sadahiro Tamiya, Tatsutoshi Nakahata, Masao MatsuokaAbstract:In adult T-cell leukemia (ATL) cells, a defective human T-cell leukemia virus type 1 (HTLV-1) provirus lacking the 5′ long terminal repeat (LTR), designated type 2 defective provirus, is frequently observed. To investigate the mechanism underlying the generation of the defective provirus, we sequenced HTLV-1 provirus integration sites from cases of ATL. In HTLV-1 Proviruses retaining both LTRs, 6-bp repeat sequences were adjacent to the 5′ and 3′ LTRs. In 8 of 12 cases with type 2 defective provirus, 6-bp repeats were identified at both ends. In five of these cases, a short repeat was bound to CA dinucleotides of the pol and env genes at the 5′ end, suggesting that these type 2 defective Proviruses were formed before integration. In four cases lacking the 6-bp repeat, short (6- to 26-bp) deletions in the host genome were identified, indicating that these defective Proviruses were generated after integration. Quantification indicated frequencies of type 2 defective provirus of less than 3.9% for two carriers, which are much lower than those seen for ATL cases (27.8%). In type 2 defective Proviruses, the second exons of the tax, rex, and p30 genes were frequently deleted, leaving Tax unable to activate NF-κB and CREB pathways. The HTLV-1 bZIP factor gene, located on the minus strand, is expressed in ATL cells with this defective provirus, and its coding sequences are intact, suggesting its significance in oncogenesis.
Tatsutoshi Nakahata - One of the best experts on this subject based on the ideXlab platform.
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preferential selection of human t cell leukemia virus type 1 provirus lacking the 5 long terminal repeat during oncogenesis
Journal of Virology, 2007Co-Authors: Maki Miyazaki, Jun-ichirou Yasunaga, Yuko Taniguchi, Sadahiro Tamiya, Tatsutoshi Nakahata, Masao MatsuokaAbstract:In adult T-cell leukemia (ATL) cells, a defective human T-cell leukemia virus type 1 (HTLV-1) provirus lacking the 5′ long terminal repeat (LTR), designated type 2 defective provirus, is frequently observed. To investigate the mechanism underlying the generation of the defective provirus, we sequenced HTLV-1 provirus integration sites from cases of ATL. In HTLV-1 Proviruses retaining both LTRs, 6-bp repeat sequences were adjacent to the 5′ and 3′ LTRs. In 8 of 12 cases with type 2 defective provirus, 6-bp repeats were identified at both ends. In five of these cases, a short repeat was bound to CA dinucleotides of the pol and env genes at the 5′ end, suggesting that these type 2 defective Proviruses were formed before integration. In four cases lacking the 6-bp repeat, short (6- to 26-bp) deletions in the host genome were identified, indicating that these defective Proviruses were generated after integration. Quantification indicated frequencies of type 2 defective provirus of less than 3.9% for two carriers, which are much lower than those seen for ATL cases (27.8%). In type 2 defective Proviruses, the second exons of the tax, rex, and p30 genes were frequently deleted, leaving Tax unable to activate NF-κB and CREB pathways. The HTLV-1 bZIP factor gene, located on the minus strand, is expressed in ATL cells with this defective provirus, and its coding sequences are intact, suggesting its significance in oncogenesis.
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Preferential Selection of Human T-Cell Leukemia Virus Type 1 Provirus Lacking the 5′ Long Terminal Repeat during Oncogenesis
Journal of Virology, 2007Co-Authors: Maki Miyazaki, Jun-ichirou Yasunaga, Yuko Taniguchi, Sadahiro Tamiya, Tatsutoshi Nakahata, Masao MatsuokaAbstract:In adult T-cell leukemia (ATL) cells, a defective human T-cell leukemia virus type 1 (HTLV-1) provirus lacking the 5′ long terminal repeat (LTR), designated type 2 defective provirus, is frequently observed. To investigate the mechanism underlying the generation of the defective provirus, we sequenced HTLV-1 provirus integration sites from cases of ATL. In HTLV-1 Proviruses retaining both LTRs, 6-bp repeat sequences were adjacent to the 5′ and 3′ LTRs. In 8 of 12 cases with type 2 defective provirus, 6-bp repeats were identified at both ends. In five of these cases, a short repeat was bound to CA dinucleotides of the pol and env genes at the 5′ end, suggesting that these type 2 defective Proviruses were formed before integration. In four cases lacking the 6-bp repeat, short (6- to 26-bp) deletions in the host genome were identified, indicating that these defective Proviruses were generated after integration. Quantification indicated frequencies of type 2 defective provirus of less than 3.9% for two carriers, which are much lower than those seen for ATL cases (27.8%). In type 2 defective Proviruses, the second exons of the tax, rex, and p30 genes were frequently deleted, leaving Tax unable to activate NF-κB and CREB pathways. The HTLV-1 bZIP factor gene, located on the minus strand, is expressed in ATL cells with this defective provirus, and its coding sequences are intact, suggesting its significance in oncogenesis.
