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  • 1
    Online Resource
    Online Resource
    Effects of CD2 locus control region sequences on gene expression by retroviral and lentiviral vectors
    American Society of Hematology ; 2001
    In:  Blood Vol. 98, No. 13 ( 2001-12-15), p. 3607-3617
    Details
    In: Blood, American Society of Hematology, Vol. 98, No. 13 ( 2001-12-15), p. 3607-3617
    Abstract: Locus control region (LCR) sequences are involved in the establishment of open chromosomal domains. To evaluate the possibility of exploiting the human CD2 LCR to regulate gene expression by Moloney murine leukemia virus (Mo-MLV)–based retroviral vectors in T cells, it was included in vectors carrying the enhanced green fluorescence protein (EGFP) reporter gene; then transduction in vitro of lymphoid and nonlymphoid cell lines was performed. Deletion of the viral enhancer in the Mo-MLV long terminal repeat was necessary to detect LCR activity in the context of these retroviral vectors. It was found that a full-length (2.1 kb), but not a truncated (1.0 kb), CD2 LCR retained the ability to modulate reporter gene expression by Mo-MLV–derived retroviral vectors, leading to a homogeneous, unimodal pattern of EGFP expression that remained unmodified in culture over time, specifically in T-cell lines; on the other hand, viral titer was strongly reduced compared with vectors not carrying the LCR. Lentiviral vectors containing the CD2 LCR could be generated at higher titers and were used to analyze its effects on gene expression in primary T cells. Subcutaneous implantation of genetically modified cells in immunodeficient mice showed that retroviral vectors carrying the CD2 LCR conferred an advantage in terms of transgene expression in vivo, compared with the parental vector, by preventing the down-modulation of EGFP expression. These findings suggest a potential application of this LCR to increase gene expression by retroviral and lentiviral vectors in T lymphocytes.
    Type of Medium: Online Resource
    ISSN: 1528-0020 , 0006-4971
    URL: Article
    DOI: 10.1182/blood.V98.13.3607
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2001
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  • 2
    Online Resource
    Online Resource
    Efficient protection of microorganisms for delivery to the intestinal tract by cellulose sulphate encapsulation
    Springer Science and Business Media LLC ; 2020
    In:  Microbial Cell Factories Vol. 19, No. 1 ( 2020-12)
    Details
    In: Microbial Cell Factories, Springer Science and Business Media LLC, Vol. 19, No. 1 ( 2020-12)
    Abstract: Gut microbiota in humans and animals play an important role in health, aiding in digestion, regulation of the immune system and protection against pathogens. Changes or imbalances in the gut microbiota (dysbiosis) have been linked to a variety of local and systemic diseases, and there is growing evidence that restoring the balance of the microbiota by delivery of probiotic microorganisms can improve health. However, orally delivered probiotic microorganisms must survive transit through lethal highly acid conditions of the stomach and bile salts in the small intestine. Current methods to protect probiotic microorganisms are still not effective enough. Results We have developed a cell encapsulation technology based on the natural polymer, cellulose sulphate (CS), that protects members of the microbiota from stomach acid and bile. Here we show that six commonly used probiotic strains (5 bacteria and 1 yeast) can be encapsulated within CS microspheres. These encapsulated strains survive low pH in vitro for at least 4 h without appreciable loss in viability as compared to their respective non-encapsulated counterparts. They also survive subsequent exposure to bile. The CS microspheres can be digested by cellulase at concentrations found in the human intestine, indicating one mechanism of release. Studies in mice that were fed CS encapsulated autofluorescing, commensal E. coli demonstrated release and colonization of the intestinal tract. Conclusion Taken together, the data suggests that CS microencapsulation can protect bacteria and yeasts from viability losses due to stomach acid, allowing the use of lower oral doses of probiotics and microbiota, whilst ensuring good intestinal delivery and release.
    Type of Medium: Online Resource
    ISSN: 1475-2859
    URL: Article
    DOI: 10.1186/s12934-020-01465-3
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
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  • 3
    Online Resource
    Online Resource
    Multiple Modifications Allow High-Titer Production of Retroviral Vectors Carrying Heterologous Regulatory Elements
    American Society for Microbiology ; 2004
    In:  Journal of Virology Vol. 78, No. 3 ( 2004-02), p. 1384-1392
    Details
    In: Journal of Virology, American Society for Microbiology, Vol. 78, No. 3 ( 2004-02), p. 1384-1392
    Abstract: Tumor-specific expression of therapeutic genes is a prerequisite in many approaches to retrovirus-mediated cancer gene therapy. However, tissue specificity is often associated with a reduction in viral titer. To overcome this problem, we constructed a series of murine leukemia virus (MLV)-based retroviral promoter conversion (ProCon) vectors carrying either the simian virus 40 poly(A) signal trimer (3pA) inserted in the 3′ long terminal repeat (LTR) of these vectors or the human cytomegalovirus enhancer region (CMVe) inserted 5′ and 3′ of the retroviral LTRs. Furthermore, an extended AT stretch/attachment site (AT/att) of wild-type MLV was introduced into the vector. In the vector-producing cells, insertion of the CMVe and/or the 3pA resulted in a three- to fourfold-enhanced marker gene expression compared to the parental vector, whereas insertion of the AT/att gave a slight decrease in expression. The combination of all three modifications had no additional effects. In contrast, however, neomycin selection of infected cells revealed only a slight increase in virus titer with vectors carrying the 3pA modification; the titer was increased by 1 with vectors containing the extended AT/att, although the viral DNA copy numbers in infected cells were similar with both types of vectors. Thus, insufficient integration rather than insufficient reverse transcription and/or production of virus RNA is the major cause for the low titer obtained with the ProCon vectors. The combination of all three modifications resulted in a 2- to 3-log increase in the virus titer. These modifications result in expression targeted ProCon vectors with titers similar to those of nonmodified MLV-based vectors.
    Type of Medium: Online Resource
    ISSN: 0022-538X , 1098-5514
    URL: Article
    DOI: 10.1128/JVI.78.3.1384-1392.2004
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2004
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  • 4
    Online Resource
    Online Resource
    The Role of a Betaretrovirus in Human Breast Cancer: Enveloping a Conundrum
    MDPI AG ; 2022
    In:  Viruses Vol. 14, No. 11 ( 2022-10-25), p. 2342-
    Details
    In: Viruses, MDPI AG, Vol. 14, No. 11 ( 2022-10-25), p. 2342-
    Abstract: Most of the evidence that a human betaretrovirus (HBRV/HMTV) highly related to mouse mammary tumour virus (MMTV) has an etiological role in breast cancer has been summarized in a recent comprehensive Special Issue of “Viruses” entitled “Human Betaretrovirus (HBRV) and Related Diseases”. Shortly after publication of this special issue, a detailed analysis of aligned env sequences was published and concluded that (i) MMTV and HBRV/HMTV cannot be distinguished on the basis of aligned env sequences and (ii) more sequence data covering the full-length env or HBRV/HMTV genomes from multiple isolates is needed. Although productive infection of human cells by MMTV (and presumably HBRV/HMTV) has been shown, it is imperative that the receptor(s) enabling HBRV/HMTV to infect human cells are defined. Moreover, there is currently no compelling data for common integration sites, in contrast to MMTV induced mammary tumorigenesis in mice, suggesting that other mechanisms of tumorigenesis are associated with HBRV/HMTV infection. These issues need to be resolved before a clear link between MMTV/HBRV/HMTV and human breast cancer can be concluded.
    Type of Medium: Online Resource
    ISSN: 1999-4915
    URL: Article
    DOI: 10.3390/v14112342
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
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  • 5
    Online Resource
    Online Resource
    Superantigen Expression Is Driven by Both Mouse Mammary Tumor Virus Long Terminal Repeat-Associated Promoters in Transgenic Mice
    American Society for Microbiology ; 2000
    In:  Journal of Virology Vol. 74, No. 6 ( 2000-03-15), p. 2900-2902
    Details
    In: Journal of Virology, American Society for Microbiology, Vol. 74, No. 6 ( 2000-03-15), p. 2900-2902
    Abstract: In addition to the usual retroviral promoter, the mouse mammary tumor virus (MMTV) long terminal repeat carries a second promoter located in the U3 region. Here we show that both of these promoters are independently able to give rise to superantigen activity in transgenic mice. The ability of multiple MMTV promoters to drive superantigen expression underscores its importance in the virus life cycle.
    Type of Medium: Online Resource
    ISSN: 0022-538X , 1098-5514
    URL: Article
    DOI: 10.1128/JVI.74.6.2900-2902.2000
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2000
    detail.hit.zdb_id: 1495529-5
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  • 6
    Online Resource
    Online Resource
    Mouse Mammary Tumor Virus Infects Human Cells
    American Association for Cancer Research (AACR) ; 2005
    In:  Cancer Research Vol. 65, No. 15 ( 2005-08-01), p. 6651-6659
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 65, No. 15 ( 2005-08-01), p. 6651-6659
    Abstract: Mouse mammary tumor virus (MMTV) has long been speculated to be involved in human breast cancer and more recently in human primary biliary cirrhosis. Despite complete proviral sequences markedly homologous to MMTV being identified in human breast cancer tissue, no convincing evidence has been presented to date that MMTV can infect human cells. Using both wild-type and a genetically marked virus (MMTV-EGFP), we show here the successful infection of a number of different human cells by MMTV. Furthermore, infection of human cells is shown to be almost as efficient as the infection of murine mammary epithelial cells. Sequencing of PCR products from integrated proviruses reveals that reverse transcription and integration of the viral genome has occurred as expected. Furthermore, sequencing of two independent MMTV proviral integration sites reveal them to be present only in the human and not in the mouse genome. Infection requires an intact MMTV envelope protein and is blocked either by heat inactivation of the virus or by specific neutralizing anti-MMTV serum, ruling out a nonspecific mechanism of viral transfer. Thus, MMTV can infect human cells and this finding provides a possible explanation for the detection by others of MMTV sequences in human breast cancer patients.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/0008-5472.CAN-04-2609
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2005
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 7
    Online Resource
    Online Resource
    Commentary regarding Gannon et al. “Viral infections and breast cancer – A current perspective”
    Elsevier BV ; 2018
    In:  Cancer Letters Vol. 424 ( 2018-06), p. 117-118
    Details
    In: Cancer Letters, Elsevier BV, Vol. 424 ( 2018-06), p. 117-118
    Type of Medium: Online Resource
    ISSN: 0304-3835
    URL: Article
    DOI: 10.1016/j.canlet.2018.03.028
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2018
    detail.hit.zdb_id: 195674-7
    detail.hit.zdb_id: 2004212-7
    SSG: 12
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  • 8
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    Online Resource
    Revisiting a role for a mammary tumor retrovirus in human breast cancer
    Wiley ; 2013
    In:  International Journal of Cancer Vol. 133, No. 7 ( 2013-10), p. 1530-1535
    Details
    In: International Journal of Cancer, Wiley, Vol. 133, No. 7 ( 2013-10), p. 1530-1535
    Abstract: There remains great controversy as to whether mouse mammary tumor virus (MMTV), the etiological agent of mammary cancer in mice, or a closely related human retrovirus, plays a role in the development of breast cancer in humans. On one hand, retroviruses such as human T‐cell lymphotropic virus and human immunodeficiency virus (HIV) are known causative agents of cancer (in the case of HIV, albeit, indirectly), but attempts to associate other retroviruses with human cancers have been difficult. A recent, high profile, example has been the postulated involvement of another mouse virus, xenotropic murine leukemia virus‐related virus, in human prostate cancer, which is now thought to be due to contamination. Here, we review some of the more recent evidence for and against the involvement of MMTV in human breast cancer and suggest future studies that may allow a definitive answer to this conundrum.
    Type of Medium: Online Resource
    ISSN: 0020-7136 , 1097-0215
    URL: Issue
    URL: Article
    DOI: 10.1002/ijc.v133.7
    DOI: 10.1002/ijc.28210
    RVK:
    XA 10000
    Language: English
    Publisher: Wiley
    Publication Date: 2013
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    detail.hit.zdb_id: 1474822-8
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  • 9
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    Online Resource
    MMTV accessory factor Naf affects cellular gene expression
    Elsevier BV ; 2006
    In:  Virology Vol. 346, No. 1 ( 2006-03), p. 139-150
    Details
    In: Virology, Elsevier BV, Vol. 346, No. 1 ( 2006-03), p. 139-150
    Type of Medium: Online Resource
    ISSN: 0042-6822
    URL: Article
    DOI: 10.1016/j.virol.2005.10.029
    RVK:
    WA 15000
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2006
    detail.hit.zdb_id: 1471925-3
    SSG: 12
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  • 10
    Online Resource
    Online Resource
    Transgene Expression Facilitated by the v- src Splice Acceptor Can Impair Replication Kinetics and Lead to Genomic Instability of Rous Sarcoma Virus-Based Vectors
    American Society for Microbiology ; 2008
    In:  Journal of Virology Vol. 82, No. 3 ( 2008-02), p. 1610-1614
    Details
    In: Journal of Virology, American Society for Microbiology, Vol. 82, No. 3 ( 2008-02), p. 1610-1614
    Abstract: Rous sarcoma virus (RSV) can be used for the simple generation of high-titer replication-competent retroviral (RCR) vectors. Retroviruses undergo frequent genomic recombination, however, and vectors with reduced replication kinetics are rapidly overgrown by mutant forms. Vector design is hence critical to vector efficacy. In this study, two different designs of RSV-based RCR vectors were evaluated. Vectors in which transgene expression was facilitated by the v- src splice acceptor were revealed to have greatly reduced replication kinetics and genomic stability in comparison to vectors in which transgene expression was mediated by an internal ribosome entry site in the 3′ untranslated region.
    Type of Medium: Online Resource
    ISSN: 0022-538X , 1098-5514
    URL: Article
    DOI: 10.1128/JVI.01734-07
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2008
    detail.hit.zdb_id: 1495529-5
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