A5058734327- HIV Research and Treatment
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- HIV/AIDS drug development and treatment
- Immunotherapy and Immune Responses
- HIV/AIDS Research and Interventions
- Macrophage Migration Inhibitory Factor
- RNA Research and Splicing
- Cytomegalovirus and herpesvirus research
- Genomics and Chromatin Dynamics
- Cell Adhesion Molecules Research
- interferon and immune responses
- Redox biology and oxidative stress
- Immune Response and Inflammation
- NF-κB Signaling Pathways
- Hematopoietic Stem Cell Transplantation
- Reproductive System and Pregnancy
- Galectins and Cancer Biology
- Phagocytosis and Immune Regulation
- Selenium in Biological Systems
- Bioinformatics and Genomic Networks
- Immune cells in cancer
- Natural Compounds in Disease Treatment
- Endoplasmic Reticulum Stress and Disease
- RNA modifications and cancer
Boston University
2015-2024
University of Massachusetts Boston
2021
Boston Medical Center
2007-2021
Kansas State University
2021
University of Michigan
2020
University Medical Center
2007-2019
Office of Infectious Diseases
2013
Czech Academy of Sciences, Institute of Microbiology
2013
Pennsylvania State University
1998-2008
Center for Molecular Medicine and Immunology
2008
Three binding sites for C/EBP proteins are found in the human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) (V. M. Tesmer, A. Rajadhyaksha, J. Babin, and Bina, Proc. Natl. Acad. Sci. USA 90:7298-7302, 1993). We have determined functional role of regulating transcription from HIV-1 LTR monocytes/macrophages. Inhibition endogenous proteins, using either an excess or a trans-dominant negative inhibitor, demonstrated that required basal activated levels promonocytic cell line...
Abstract HIV-1 is an enveloped retrovirus that acquires its outer membrane as the virion exits cell. Because of association apoptosis with progression AIDS, HIV-1-infected T cells or macrophages might be expected to express elevated levels surface phosphatidylserine (PS), a hallmark programmed cell death. Virions produced by these would also predicted have PS on their envelopes. In this study, data are presented support hypothesis and suggest required for macrophage infection. The...
The importance of CCAAT/enhancer binding proteins (C/EBPs) and sites for HIV-1 replication in primary macrophages, T cell lines CD4 + cells was examined. When overexpressing the C/EBP dominant-negative protein LIP were infected with HIV-1, occurred Jurkat but not U937 promonocytes, demonstrating a requirement activators by only promonocytes. Primary macrophages did support harboring mutant long terminal repeat Jurkat, H9 supported wild-type equally well. Thus is also confined to...
Analysis of cDNA and genomic clones shows that the murine Ig/EBP (C/EBPy) gene encodes a small protein with predicted molecular weight 16.4 kDa which contains C/EBP family basic leucine zipper do- mains but lacks transcriptional activation domains present in (C/EBPa)and NF-IL6 (C/EBPP).In transfection assays is neither an activator nor repressor transcription; however, inhibits ability (C/EBPP) (C/EBPoc), acting as transdominant negative regulator.Thus resembles LIP, another nega- tive...
Mumps virus (MuV), a rubulavirus of the paramyxovirus family, causes acute infections in humans. MuV has seven genes including small hydrophobic (SH) gene, which encodes type I membrane protein 57 amino acid residues. The function SH is not clear, although its expression necessary for growth tissue culture cells. It speculated that plays role viral pathogenesis. Simian 5 (SV5), closely related rubulavirus, 44-amino-acid-residue protein. Recombinant SV5 lacking gene (rSV5DeltaSH) viable and...
Human immunodeficiency virus (HIV) transcription requires virally encoded Tat and the P-TEFb protein complex, which together associate with Tat-activating region, a structured region in nascent transcript. phosphorylates Proteins elongation including RNA polymerase II (pol II), to stimulate overcome premature termination. However, status of complex on HIV long terminal repeat (LTR) repressed state is not known. Chromatin immunoprecipitation demonstrated that NELF, negative factor, was...
HIV-1 is transmitted between T cells through the release of cell-free particles and cell-cell contact. Cell-to-cell transmission more efficient than virus transmission, mediates resistance to immune responses, facilitates spread among cells. However, whether HIV cell-to-cell influences establishment latency has not been carefully explored. We developed an model based on directly resting CD4+ by This recapitulates in T-cell-dense anatomical compartments. demonstrate that productively infected...
HIV-1 acquisition occurs most commonly after sexual contact. To establish infection, must infect cells that support high-level replication, namely CD4+ T cells, which are absent from the outermost genital epithelium. Dendritic (DCs), present in mucosal epithelia, potentially facilitate acquisition. We show vaginal epithelial DCs, termed CD1a+ VEDCs, unlike other blood- and tissue-derived DCs because they express langerin but not DC-SIGN, skin-based langerin+ DC subset Langerhans (LCs), do...
Epidemiological studies suggest a correlation between severity of acquired immunodeficiency syndrome (AIDS) and selenium deficiency, indicating protective role for this anti-oxidant during HIV infection. Here we demonstrate that thioredoxin reductase-1 (TR1), selenium-containing pyridine nucleotide-disulfide oxidoreductase reduces protein disulfides to free thiols, negatively regulates the activity HIV-1 encoded transcriptional activator, Tat, in human macrophages. We used small interfering...
Abstract Chronic opioid usage not only causes addiction behavior through the central nervous system, but also modulates peripheral immune system. However, how impacts system is still barely characterized systematically. In order to understand modulatory effect of opioids in an unbiased way, here we perform single-cell RNA sequencing (scRNA-seq) blood mononuclear cells from opioid-dependent individuals and controls show that chronic evokes widespread suppression antiviral gene program naive...
Treatment for HIV has relied on the use of antiretroviral agents that can be subject to development resistant viruses. The study inhibitors directed against cellular proteins required replication is therefore growing interest. Inducible T cell kinase (ITK) a Tec family tyrosine regulates receptor (TCR)-induced activation PLCγ-1, Ca 2+ mobilization and transcription factor activation, actin rearrangement downstream both TCR chemokine receptors. Because productive infection cells with requires...
Long-lived latent HIV-infected cells lead to the rebound of virus replication following antiretroviral treatment interruption and present a major barrier eliminating HIV infection. These reservoirs, which include quiescent memory T tissue-resident macrophages, represent subset with decreased or inactive proviral transcription. transcription is regulated at multiple levels including initiation, polymerase recruitment, elongation, chromatin organization. How these biochemical processes are...
Significance Understanding mechanisms that control HIV expression will provide insight into replication, latency, and pathogenesis. In particular, which is a major barrier to cure, maintained by combinatorial regulate transcription. A functional screen was employed explore transcriptional networks HIV. These studies identified novel transcription factors influence provided an appreciation intrinsic activation repression of different strains.
Expression of phosphatidylserine (PS) on the surface both macrophages and their apoptotic targets is required for efficient phagocytosis. Monocytes, precursors macrophages, do not express PS efficiently phagocytose cells. We report here that appears human monocytic U937 cells primary monocytes as they differentiate in culture acquire ability to thymocytes. Phagocytosis was blocked by pretreating either target or phagocyte with annexin V mask CD14-dependent. PS, like other events...
Viral protein R (Vpr) is an HIV-1 accessory whose function remains poorly understood. In this report, we sought to determine the requirement of Vpr for facilitating infection monocyte-derived dendritic cells (MDDCs), one first cell types encounter virus in peripheral mucosal tissues. characterize a significant restriction Vpr-deficient replication and spread MDDCs alone cell-to-cell MDDC-CD4+ T cocultures. This was observed single round rescued by expression trans incoming virion....
Bone marrow stromal cells have well documented effects on the production of B lymphocytes, but whether or not cell signals are involved in pre-B to transition is unclear. The potential two lines, S10 and S17, this process was examined. Initial experiments, using a short term liquid culture, indicated that S17 stroma efficiently supported generation clonable (B lymphocyte CFU) from their immediate precursors fresh bone marrow. contribution macrophages other accessory those experiments...
Proper cytokine gene expression is essential in development, homeostasis and immune responses. Studies on the transcriptional control of genes have mostly focused highly researched transcription factors (TFs) cytokines, resulting an incomplete portrait regulation. Here, we used enhanced yeast one-hybrid (eY1H) assays to derive a comprehensive network comprising 1380 interactions between 265 TFs 108 promoters. Our eY1H-derived greatly expands known repertoire TF-cytokine set regulate genes....