Open Access. Powered by Scholars. Published by Universities.®
Articles 1 - 16 of 16
Full-Text Articles in Medicine and Health Sciences
The Role Of Indoleamine 2,3-Dioxygenase In Lp-Bpm5 Murine Retroviral Disease Progression, Megan A. O'Connor, William R. Green
The Role Of Indoleamine 2,3-Dioxygenase In Lp-Bpm5 Murine Retroviral Disease Progression, Megan A. O'Connor, William R. Green
Dartmouth Scholarship
Indoleamine 2,3-dioxygenase (IDO) is an immunomodulatory intracellular enzyme involved in tryptophan degradation. IDO is induced during cancer and microbial infections by cytokines, ligation of co-stimulatory molecules and/or activation of pattern recognition receptors, ultimately leading to modulation of the immune response. LP-BM5 murine retroviral infection induces murine AIDS (MAIDS), which is characterized by profound and broad immunosuppression of T- and B-cell responses. Our lab has previously described multiple mechanisms regulating the development of immunodeficiency of LP-BM5-induced disease, including Programmed Death 1 (PD-1), IL-10, and T-regulatory (Treg) cells. Immunosuppressive roles of IDO have been demonstrated in other retroviral models, suggesting a possible …
Molecular Epidemiology Of Hiv-Associated Tuberculosis In Dar Es Salaam, Tanzania: Strain Predominance, Clustering, And Polyclonal Disease, Lisa V. Adams, Barry N. Kreiswirth, Robert D. Arbeit, Hanna Soini, Lillian Mtei, Mecky Matee, Muhammad Bakari, Timothy Lahey, Wendy Wieland-Alter
Molecular Epidemiology Of Hiv-Associated Tuberculosis In Dar Es Salaam, Tanzania: Strain Predominance, Clustering, And Polyclonal Disease, Lisa V. Adams, Barry N. Kreiswirth, Robert D. Arbeit, Hanna Soini, Lillian Mtei, Mecky Matee, Muhammad Bakari, Timothy Lahey, Wendy Wieland-Alter
Dartmouth Scholarship
Molecular typing of Mycobacterium tuberculosis can be used to elucidate the epidemiology of tuberculosis, including the rates of clustering, the frequency of polyclonal disease, and the distribution of genotypic families. We performed IS6110 typing and spoligotyping on M. tuberculosis strains isolated from HIV-infected subjects at baseline or during follow-up in the DarDar Trial in Tanzania and on selected community isolates. Clustering occurred in 203 (74%) of 275 subjects: 124 (80%) of 155 HIV-infected subjects with baseline isolates, 56 (69%) of 81 HIV-infected subjects with endpoint isolates, and 23 (59%) of 39 community controls. Overall, 113 (41%) subjects had an …
Impaired Memory Cd8 T-Cell Responses Against An Immunodominant Retroviral Cryptic Epitope, Melanie R. Rutkowski, Cynthia A. Stevens, William R. Green
Impaired Memory Cd8 T-Cell Responses Against An Immunodominant Retroviral Cryptic Epitope, Melanie R. Rutkowski, Cynthia A. Stevens, William R. Green
Dartmouth Scholarship
The immunodominant cryptic epitope SYNTGRFPPL, encoded within open reading frame 2 of the LP-BM5 retroviral gag gene, is critical for protection against retroviral-induced pathogenesis. The goal of this study was to dissect the memory response against this unique immunodominant cryptic epitope. Unlike the protective acute effector population of SYNTGRFPPL-specific CD8 T cells, long-lived SYNTGRFPPL-specific CD8 T cells lacked the ability to protect susceptible mice infected with LP-BM5 retrovirus. Compared to memory CD8 T cells against a conventional epitope with similar MHC-I specificity, primed and restimulated using similar conditions, long-lived SYNTGRFPPL-specific CD8 T cells were impaired in their ability to recall …
Primary Human Mammary Epithelial Cells Endocytose Hiv-1 And Facilitate Viral Infection Of Cd4+ T Lymphocytes, Stephanie M. Dorosko, Ruth I. Connor
Primary Human Mammary Epithelial Cells Endocytose Hiv-1 And Facilitate Viral Infection Of Cd4+ T Lymphocytes, Stephanie M. Dorosko, Ruth I. Connor
Dartmouth Scholarship
The contribution of mammary epithelial cells (MEC) to human immunodeficiency virus type 1 (HIV-1) in breast milk remains largely unknown. While breast milk contains CD4(+) cells throughout the breast-feeding period, it is not known whether MEC directly support HIV-1 infection or facilitate infection of CD4(+) cells in the breast compartment. This study evaluated primary human MEC for direct infection with HIV-1 and for indirect transfer of infection to CD4(+) target cells. Primary human MEC were isolated and assessed for expression of HIV-1 receptors. MEC were exposed to CCR5-, CXCR4- and dual-tropic strains of HIV-1 and evaluated for viral reverse transcription …
Human Uterine Natural Killer Cells But Not Blood Natural Killer Cells Inhibit Human Immunodeficiency Virus Type 1 Infection By Secretion Of Cxcl12, Teddy F. Mselle, Aexandra L. Howell, Mimi Ghosh, Charles R. Wira, Charles L. Sentman
Human Uterine Natural Killer Cells But Not Blood Natural Killer Cells Inhibit Human Immunodeficiency Virus Type 1 Infection By Secretion Of Cxcl12, Teddy F. Mselle, Aexandra L. Howell, Mimi Ghosh, Charles R. Wira, Charles L. Sentman
Dartmouth Scholarship
Natural killer (NK) cells derived from the human female reproductive tract (FRT) are phenotypically and functionally distinct from those obtained from peripheral blood. Because the FRT is a primary site of human immunodeficiency virus type 1 (HIV-1) infection in women, we determined whether soluble factors secreted by uterine-derived NK (uNK) cells inhibit HIV-1 infection. Clonal populations of uNK cells were activated with interleukin-12 (IL-12) and IL-15, and conditioned media (CM) from these cultures evaluated for their ability to inhibit infection of cells by HIV-1IIIB, HIV-1NL4.3, and HIV-1HC4 (X4-tropic) or HIV-1BaL (R5-tropic) viruses. We found …
Human Immunodeficiency Virus Type 1-Induced Macrophage Gene Expression Includes The P21 Gene, A Target For Viral Regulation, Nancy Vazquez, Teresa Greenwell-Wild, Nancy J. Marinos, William D. Swaim, Salvador Nares, David E. Ott, Ulrich Schubert, Peter Henklein, Jan M. Orenstein, Michael B. Sporn, Sharon M. Wahl
Human Immunodeficiency Virus Type 1-Induced Macrophage Gene Expression Includes The P21 Gene, A Target For Viral Regulation, Nancy Vazquez, Teresa Greenwell-Wild, Nancy J. Marinos, William D. Swaim, Salvador Nares, David E. Ott, Ulrich Schubert, Peter Henklein, Jan M. Orenstein, Michael B. Sporn, Sharon M. Wahl
Dartmouth Scholarship
In contrast to CD4+ T cells, human immunodeficiency virus type 1 (HIV-1)-infected macrophages typically resist cell death, support viral replication, and consequently, may facilitate HIV-1 transmission. To elucidate how the virus commandeers the macrophage's intracellular machinery for its benefit, we analyzed HIV-1-infected human macrophages for virus-induced gene transcription by using multiple parameters, including cDNA expression arrays. HIV-1 infection induced the transcriptional regulation of genes associated with host defense, signal transduction, apoptosis, and the cell cycle, among which the cyclin-dependent kinase inhibitor 1A (CDKN1A/p21) gene was the most prominent. p21 mRNA and protein expression followed a bimodal pattern which was …
Role Of A Cytotoxic-T-Lymphocyte Epitope-Defined, Alternative Gag Open Reading Frame In The Pathogenesis Of A Murine Retrovirus-Induced Immunodeficiency Syndrome, Arti Gaur, William R. Green
Role Of A Cytotoxic-T-Lymphocyte Epitope-Defined, Alternative Gag Open Reading Frame In The Pathogenesis Of A Murine Retrovirus-Induced Immunodeficiency Syndrome, Arti Gaur, William R. Green
Dartmouth Scholarship
LP-BM5 murine leukemia virus-infected C57BL/6 mice develop profound immunodeficiency and B-cell lymphomas. The LP-BM5 complex contains a mixture of defective (BM5def) and replication-competent helper viruses among which BM5def is the primary causative agent of disease. The BM5def primary open reading frame (ORF1) encodes the single gag precursor protein (Pr60gag). Our lab has recently demonstrated that a novel immunodominant cytotoxic-T-lymphocyte (CTL) epitope (SYNTGRFPPL) is expressed from a +1-nucleotide translational open reading frame of BM5def during the course of normal retrovirus expression. The SYNTGRFPPL CTL epitope may be generated from either of two initiation methionines present, ORF2a or ORF2b, located …
Cd40-Associated Traf 6 Signaling Is Required For Disease Induction In A Retrovirus-Induced Murine Immunodeficiency, Kathy A. Green, Cory L. Ahonen, W. James Cook, William R. Green
Cd40-Associated Traf 6 Signaling Is Required For Disease Induction In A Retrovirus-Induced Murine Immunodeficiency, Kathy A. Green, Cory L. Ahonen, W. James Cook, William R. Green
Dartmouth Scholarship
LP-BM5 retrovirus-infected C57BL/6 mice develop splenomegaly, lymphadenopathy, hypergammaglobulinemia, and immunodeficiency; thus, this disease has been named mouse AIDS. In this syndrome, CD154/CD40 interactions are required for but do not mediate disease by upregulation of CD80 or CD86. We report here that there is nonetheless a necessity for CD40 signaling competence, specifically an intact tumor necrosis factor receptor-associated factor 6 (TRAF 6) binding site.
Clinical And Epidemiological Correlates Of Genotypes Within The Mycobacterium Avium Complex Defined By Restriction And Sequence Analysis Of Hsp65, Sandra C. Smole, Fionnuala Mcaleese, Jutamas Ngampasutadol, C. Fordham Von Reyn, Robert D. Arbeit
Clinical And Epidemiological Correlates Of Genotypes Within The Mycobacterium Avium Complex Defined By Restriction And Sequence Analysis Of Hsp65, Sandra C. Smole, Fionnuala Mcaleese, Jutamas Ngampasutadol, C. Fordham Von Reyn, Robert D. Arbeit
Dartmouth Scholarship
Species identification of isolates of the Mycobacterium avium complex (MAC) remains a difficult task. Although M. avium and Mycobacterium intracellulare can be identified with expensive, commercially available probes, many MAC isolates remain unresolved, including those representing Mycobacterium lentiflavum as well as other potentially undefined species. PCR restriction analysis (PRA) of the hsp65 gene has been proposed as a rapid and inexpensive approach. We applied PRA to 278 MAC isolates, including 126 from blood of human immunodeficiency virus (HIV)-infected patients, 59 from sputum of HIV-negative patients with chronic obstructive pulmonary disease, 88 from environmental sources, and 5 pulmonary isolates from …
Characterization Of The Cd154-Positive And Cd40-Positive Cellular Subsets Required For Pathogenesis In Retrovirus-Induced Murine Immunodeficiency, Kathy A. Green, Randolph J. Noelle, Brigit G. Durell, William R. Green
Characterization Of The Cd154-Positive And Cd40-Positive Cellular Subsets Required For Pathogenesis In Retrovirus-Induced Murine Immunodeficiency, Kathy A. Green, Randolph J. Noelle, Brigit G. Durell, William R. Green
Dartmouth Scholarship
Genetically susceptible C57BL/6 (B6) mice that are infected with the LP-BM5 isolate of murine retroviruses develop profound splenomegaly, lymphadenopathy, hypergammaglobulinemia, terminal B-cell lymphomas, and an immunodeficiency state bearing many similarities to the pathologies seen in AIDS. Because of these similarities, this syndrome has been called murine AIDS (MAIDS). We have previously shown that CD154 (CD40 ligand)-CD40 molecular interactions are required both for the initiation and progression of MAIDS. Thus, in vivo anti-CD154 monoclonal antibody (MAb) treatment inhibited MAIDS symptoms in LP-BM5-infected wild-type mice when either a short course of anti-CD154 MAb treatment was started on the day of infection or …
Adoptive Transfer Of Polyclonal And Cloned Cytolytic T Lymphocytes (Ctl) Specific For Mouse Aids-Associated Tumors Is Effective In Preserving Ctl Responses: A Measure Of Protection Against Lp-Bm5 Retrovirus-Induced Immunodeficiency., William R. Green, Kathy A. Green, Karen M. Crassi
Adoptive Transfer Of Polyclonal And Cloned Cytolytic T Lymphocytes (Ctl) Specific For Mouse Aids-Associated Tumors Is Effective In Preserving Ctl Responses: A Measure Of Protection Against Lp-Bm5 Retrovirus-Induced Immunodeficiency., William R. Green, Kathy A. Green, Karen M. Crassi
Dartmouth Scholarship
Cytolytic T lymphocytes (CTL) can be raised against C57BL/6 B-cell lymphomas from mice with LP-BM5 murine leukemia virus-induced AIDS (MAIDS). Adoptive transfer of polyclonal anti-MAIDS tumor CTL or two CTL clones specific for the B6-1710 MAIDS lymphoma caused preservation of major histocompatibility complex-restricted and allogeneic CTL responses, which may be interpreted as indices of protection from LP-BM5 murine leukemia virus-induced immunodeficiency.
Molecular Cloning Of Infectious Ecotropic Murine Leukemia Virus Ak7 From An Emv-14-Positive Akxl-5 Mouse And The Resistance Of Ak7 To Recognition By Cytotoxic T Lymphocytes., Hillary D. White, William R. Green, Nuria R. Giné
Molecular Cloning Of Infectious Ecotropic Murine Leukemia Virus Ak7 From An Emv-14-Positive Akxl-5 Mouse And The Resistance Of Ak7 To Recognition By Cytotoxic T Lymphocytes., Hillary D. White, William R. Green, Nuria R. Giné
Dartmouth Scholarship
The AKXL-5 recombinant inbred mouse strain is positive for the endogenous ecotropic murine leukemia virus emv-14, the only emv present in its germ line. emv-14 is of particular interest because spleen cells expressing emv-14 virus escape recognition by anti-AKR/Gross virus-specific cytotoxic T lymphocytes. We report here the isolation and characterization of a replication-competent emv clone, pAK7, derived from an AKXL-5 mouse. This clone is novel in that it encodes a variant ecotropic murine leukemia virus that, when expressed in SC.Kb target cells, fails to be recognized efficiently by anti-AKR/Gross virus cytotoxic T lymphocytes. The pAK7 clone can therefore be used …
Cloning And Characterization Of Subunits Of The T-Cell Receptor And Murine Leukemia Virus Enhancer Core-Binding Factor., Shuwen Wang, Qing Wang, Barbara E. Crute, Irena N. Melnikova, Susanna R. Keller, Nancy A. Speck
Cloning And Characterization Of Subunits Of The T-Cell Receptor And Murine Leukemia Virus Enhancer Core-Binding Factor., Shuwen Wang, Qing Wang, Barbara E. Crute, Irena N. Melnikova, Susanna R. Keller, Nancy A. Speck
Dartmouth Scholarship
Moloney murine leukemia virus causes thymic leukemias when injected into newborn mice. A major determinant of the thymic disease specificity of Moloney virus genetically maps to the conserved viral core motif in the Moloney virus enhancer. Point mutations introduced into the core site significantly shifted the disease specificity of the Moloney virus from thymic leukemia to erythroid leukemia (N.A. Speck, B. Renjifo, E. Golemis, T.N. Fredrickson, J.W. Hartley, and N. Hopkins, Genes Dev. 4:233-242, 1990). We previously reported the purification of core-binding factors (CBF) from calf thymus nuclei (S. Wang and N.A. Speck, Mol. Cell. Biol. 12:89-102, 1992). CBF binds …
Sequence Specificity Of The Core-Binding Factor, Irena N. Melnikova, Barbara E. Crute, Shuwen Wang, Nancy A. Speck
Sequence Specificity Of The Core-Binding Factor, Irena N. Melnikova, Barbara E. Crute, Shuwen Wang, Nancy A. Speck
Dartmouth Scholarship
The core-binding factor (CBF) binds the conserved core motif in mammalian type C retrovirus enhancers. We analyzed the phosphate contacts made by CBF on the Moloney murine leukemia virus enhancer by ethylation interference assay. The phosphate contacts span 9 bp centered around the consensus core site. To examine the sequence preferences for CBF binding, we employed the technique of selected and amplified binding sequence footprinting (T. K. Blackwell and H. Weintraub, Science 250:1104-1110, 1990). The consensus binding site for CBF defined by selected and amplified binding sequence footprinting is PyGPyG GTPy.
Two Factors That Bind To Highly Conserved Sequences In Mammalian Type C Retroviral Enhancers., Nancy R. Manley, Mary M. O'Connell, Wanwen Sun, Nancy A. Speck, Nancy Hopkins
Two Factors That Bind To Highly Conserved Sequences In Mammalian Type C Retroviral Enhancers., Nancy R. Manley, Mary M. O'Connell, Wanwen Sun, Nancy A. Speck, Nancy Hopkins
Dartmouth Scholarship
The transcriptional enhancers of the Moloney and Friend murine leukemia viruses (MLV) are important determinants of viral pathogenicity. We used electrophoretic mobility shift and methylation interference assays to study nuclear factors which bind to a region of these enhancers whose sequence is identical between Moloney and Friend viruses and particularly highly conserved among 35 mammalian type C retroviruses whose enhancer sequences have been aligned (E. Golemis, N. A. Speck, and N. Hopkins, J. Virol. 64:534-542, 1990). Previous studies identified sites for the leukemia virus factor b (LVb) and core proteins in this region (N. A. Speck and D. Baltimore, Mol. …
Characterization Of A Protein That Binds Multiple Sequences In Mammalian Type C Retrovirus Enhancers., Wanwen Sun, Mary M. O'Connell, Nancy A. Speck
Characterization Of A Protein That Binds Multiple Sequences In Mammalian Type C Retrovirus Enhancers., Wanwen Sun, Mary M. O'Connell, Nancy A. Speck
Dartmouth Scholarship
Mammalian type C retrovirus enhancer factor 1 (MCREF-1) is a nuclear protein that binds several directly repeated sequences (CNGGN6CNGG) in the Moloney and Friend murine leukemia virus (MLV) enhancers (N. R. Manley, M. O'Connell, W. Sun, N. A. Speck, and N. Hopkins, J. Virol. 67:1967-1975, 1993). In this paper, we describe the partial purification of MCREF-1 from calf thymus nuclei and further characterize the binding properties of MCREF-1. MCREF-1 binds four sites in the Moloney MLV enhancer and three sites in the Friend MLV enhancer. Ethylation interference analysis suggests that the MCREF-1 binding site spans two adjacent minor grooves of …