Murine acquired immunodeficiency syndrome (MAIDS) induced by LP-BM5 murine leukemia virus is used as a model of human immunodeficiency virus (HIV)-related neurologic dysfunction. Mice infected with LP-BM5 have mnemonic abnormalities (i.e., spontaneous alternation behavior in the Y-maze and performance in the Morris water maze) and biochemical alternations (i.e., cytokines, platelet-activating factor, quinolinate, glutamate and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor) that produce neurologic symptoms similar to those observed in HIV-related neurologic dysfunction. To identify proteins associated with dysmnesia in the MAIDS model, we examined the expression of neuronal proteins in LP-BM5-infected mice using two-dimensional polyacrylamide gel electrophoresis (2-DE). Neuronal protein expression in LP-BM5-infected mice was compared with that in non-infected mice using the Image Master 2D. We detected approximately 800 protein spots, of which 35 were distinguishable between non-infected and LP-BM5-infected mice. Most of these spots were downregulated in LP-BM5-infected mice. Three of the spots were identified as 14-3-3 protein zeta/delta, synapsin 2 and protein disulfide isomerase using a capillary nanoliquid chromatography tandem mass spectrometric system. We verified the expression levels of these proteins by Western blot. Analysis of these 35 spots could provide insight into mechanisms of dysmnesia in the MAIDS model of HIV-related neuronal dysfunction.
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http://dx.doi.org/10.1016/j.neulet.2007.05.059 | DOI Listing |
Virology
December 2024
Geisel School of Medicine at Dartmouth, Lebanon, NH, 03756, USA.
We have shown the induction of CD11bLy6C monocytic myeloid-derived suppressor cells (M-MDSCs) during infection of B6 mice by LP-BM5 immunodeficiency-inducing retrovirus. We published that the molecular mechanisms of these M-MDSCs vary, and depend on the cell type targeted by the suppression -defined by use of biochemical inhibitors, mouse M-MDSCs knock-out strains and blocking antibodies. These M-MDSCs suppressed proliferation and function of T cells, via nitric oxide synthase/nitric oxide; and that of B cells, ∼50% via INOS/NO along with the negative checkpoint regulator VISTA, reactive nitrogen and oxygen species, and other soluble mediators.
View Article and Find Full Text PDFBiochim Biophys Acta Mol Basis Dis
December 2020
Department of Biomolecular Sciences, University of Urbino Carlo Bo, Via Saffi 2, 61029 Urbino, Italy.
Excessive production of immunoglobulins (Ig) causes endoplasmic reticulum (ER) stress and triggers the unfolded protein response (UPR). Hypergammaglobulinemia and lymphadenopathy are hallmarks of murine AIDS that develops in mice infected with the LP-BM5 murine leukemia retrovirus complex. In these mice, Th2 polarization and aberrant humoral response have been previously correlated to altered intracellular redox homeostasis.
View Article and Find Full Text PDFImmunohorizons
March 2018
Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756; and
Our laboratory demonstrated that infection with the murine retrovirus LP-BM5 results in increased numbers of monocytic myeloid-derived suppressor cells (M-MDSCs) and that these M-MDSCs suppress not only T but also B cell responses. Because of the paucity of studies regarding the effects of MDSCs in general on B cells, we focused on these understudied B cell targets for M-MDSC effects on B cell phenotypic and functional parameters. M-MDSCs specifically decreased the proliferation of transitional type 2 (T2) B cells in response to polyclonal stimulation but increased germinal center and Ab-secreting B cell proportions and class-switched Ig production.
View Article and Find Full Text PDFJ Neuroimmunol
June 2018
University of New England, College of Osteopathic Medicine, Biddeford, ME 04005, USA. Electronic address:
J Neuroinflammation
March 2018
Department of Medicine, Neurovirology Laboratory, University of Minnesota Medical School, 3-107 Microbiology Research Facility, 689 23rd Ave. S.E, Minneapolis, MN, 55455, USA.
Background: Peripheral neuropathy is currently the most common neurological complication in HIV-infected individuals, occurring in 35-50% of patients undergoing combination anti-retroviral therapy. Data have shown that distal symmetric polyneuropathy develops in mice by 6 weeks following infection with the LP-BM5 retrovirus mixture. Previous work from our laboratory has demonstrated that glial cells modulate antiviral T-cell effector responses through the programmed death (PD)-1: PD-L1 pathway, thereby limiting the deleterious consequences of unrestrained neuroinflammation.
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