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- KSHV (2)
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Articles 1 - 8 of 8
Full-Text Articles in Cell and Developmental Biology
Host-Level Susceptibility And Irf1 Expression Influence The Ability Of Ifn-Γ To Inhibit Kshv Infection In B Lymphocytes, Nedaa Alomari, Jennifer Totonchy
Host-Level Susceptibility And Irf1 Expression Influence The Ability Of Ifn-Γ To Inhibit Kshv Infection In B Lymphocytes, Nedaa Alomari, Jennifer Totonchy
Pharmacy Faculty Articles and Research
Kaposi’s sarcoma-associated herpesvirus (KSHV) is associated with vascular endothelial cell tumor, Kaposi’s sarcoma (KS) and lymphoproliferative disorder, multicentric Castleman’s disease (MCD), primary effusion lymphoma (PEL) and KSHV inflammatory cytokine syndrome (KICS). Dysregulation of proinflammatory cytokines is found in most KSHV associated diseases. However, little is known about the role of host microenvironment in the regulation of KSHV establishment in B cells. In the present study, we demonstrated that IFN-γ has a strong inhibitory effect on KSHV infection but only in a subset of tonsil-derived lymphocyte samples that are intrinsically more susceptible to infection, contain higher proportions of naïve B cells, …
Conformational Flexibility And Local Frustration In The Functional States Of The Sars-Cov-2 Spike B.1.1.7 And B.1.351 Variants: Mutation-Induced Allosteric Modulation Mechanism Of Functional Dynamics And Protein Stability, Gennady M. Verkhivker
Mathematics, Physics, and Computer Science Faculty Articles and Research
Structural and functional studies of the SARS-CoV-2 spike proteins have recently determined distinct functional states of the B.1.1.7 and B.1.351 spike variants, providing a molecular framework for understanding the mechanisms that link the effect of mutations with the enhanced virus infectivity and transmissibility. A detailed dynamic and energetic analysis of these variants was undertaken in the present work to quantify the effects of different mutations on functional conformational changes and stability of the SARS-CoV-2 spike protein. We employed the efficient and accurate coarse-grained (CG) simulations of multiple functional states of the D614G mutant, B.1.1.7 and B.1.351 spike variants to characterize …
Suppression Of Dc-Sign And Gh Reveals Complex, Subset-Specific Mechanisms For Kshv Entry In Primary B Lymphocytes, Nancy Palmerin, Farizeh Aalam, Romina Nabiee, Murali Muniraju, Javier Gordon Ogembo, Jennifer Totonchy
Suppression Of Dc-Sign And Gh Reveals Complex, Subset-Specific Mechanisms For Kshv Entry In Primary B Lymphocytes, Nancy Palmerin, Farizeh Aalam, Romina Nabiee, Murali Muniraju, Javier Gordon Ogembo, Jennifer Totonchy
Pharmacy Faculty Articles and Research
Kaposi sarcoma-associated herpesvirus (KSHV) is the causative agent of multiple cancers in immunocompromised patients including two lymphoproliferative disorders associated with KSHV infection of B lymphocytes. Despite many years of research into the pathogenesis of KSHV associated diseases, basic questions related to KSHV molecular virology remain unresolved. One such unresolved question is the cellular receptors and viral glycoproteins needed for KSHV entry into primary B lymphocytes. In this study, we assess the contributions of KSHV glycoprotein H (gH) and the cellular receptor DC-SIGN to KSHV infection in tonsil-derived B lymphocytes. Our results show that (1) neither KSHV-gH nor DC-SIGN are essential …
A Multivalent Kaposi Sarcoma-Associated Herpesvirus-Like Particle Vaccine Capable Of Eliciting High Titers Of Neutralizing Antibodies In Immunized Rabbits, David H. Mulama, Lorraine Z. Mustvunguma, Jennifer Totonchy, Peng Ye, Joslyn Foley, Gabriela M. Escalante, Esther Rodriguez, Ramina Nabiee, Murali Muniraju, Felix Wussow, Anne K. Barasa, Javier Gordon Ogembo
A Multivalent Kaposi Sarcoma-Associated Herpesvirus-Like Particle Vaccine Capable Of Eliciting High Titers Of Neutralizing Antibodies In Immunized Rabbits, David H. Mulama, Lorraine Z. Mustvunguma, Jennifer Totonchy, Peng Ye, Joslyn Foley, Gabriela M. Escalante, Esther Rodriguez, Ramina Nabiee, Murali Muniraju, Felix Wussow, Anne K. Barasa, Javier Gordon Ogembo
Pharmacy Faculty Articles and Research
Kaposi sarcoma-associated herpesvirus (KSHV) is an emerging pathogen and the causative agent of multiple cancers in immunocompromised patients. To date, there is no licensed prophylactic KSHV vaccine. In this study, we generated a novel subunit vaccine that incorporates four key KSHV envelope glycoproteins required for viral entry in diverse cell types (gpK8.1, gB, and gH/gL) into a single multivalent KSHV-like particle (KSHV-LP). Purified KSHV-LPs were similar in size, shape, and morphology to KSHV virions. Vaccination of rabbits with adjuvanted KSHV-LPs generated strong glycoprotein-specific antibody responses, and purified immunoglobulins from KSHV-LP-immunized rabbits neutralized KSHV infection in epithelial, endothelial, fibroblast, and B …
Does Persistent Hiv Replication Explain Continued Lymphoma Incidence In The Era Of Effective Antiretroviral Therapy?, Jennifer Totonchy, Ethel Cesarman
Does Persistent Hiv Replication Explain Continued Lymphoma Incidence In The Era Of Effective Antiretroviral Therapy?, Jennifer Totonchy, Ethel Cesarman
Pharmacy Faculty Articles and Research
Non-Hodgkin lymphomas are highly increased in incidence in individuals infected with HIV, and this continues to be the case in spite of highly effective combined antiretroviral therapy (cART). New evidence has demonstrated that while successful virtual recovery of CD4 counts and elimination of HIV from peripheral blood can be achieved with cART, viral replication can still occur in lymphoid tissues. In addition, recent studies have suggested that adipose tissue provides an additional reservoir for HIV-infected macrophages and T lymphocytes even in the context of successful cART therapy. In this review article, we discuss possible mechanisms leading to the development of …
Cationic Cell-Penetrating Peptides Are Potent Furin Inhibitors, Bruno Ramos-Molina, Adam N. Lick, Amir Nasrolahi Shirazi, Donghoon Oh, Rakesh Tiwari, Naglaa Salem El-Sayed, Keykavous Parang, Iris Lindberg
Cationic Cell-Penetrating Peptides Are Potent Furin Inhibitors, Bruno Ramos-Molina, Adam N. Lick, Amir Nasrolahi Shirazi, Donghoon Oh, Rakesh Tiwari, Naglaa Salem El-Sayed, Keykavous Parang, Iris Lindberg
Pharmacy Faculty Articles and Research
Cationic cell-penetrating peptides have been widely used to enhance the intracellular delivery of various types of cargoes, such as drugs and proteins. These reagents are chemically similar to the multi-basic peptides that are known to be potent proprotein convertase inhibitors. Here, we report that both HIV-1 TAT47-57 peptide and the Chariot reagent are micromolar inhibitors of furin activity in vitro. In agreement, HIV-1 TAT47-57 reduced HT1080 cell migration, thought to be mediated by proprotein convertases, by 25%. In addition, cyclic polyarginine peptides containing hydrophobic moieties which have been previously used as transfection reagents also exhibited potent furin inhibition in vitro …
Kaposi Sarcoma Herpesvirus Induces Ho-1 During De Novo Infection Of Endothelial Cells Via Viral Mirna-Dependent And -Independent Mechanisms, Sara Botto, Jennifer Totonchy, Jean K. Gustin, Ashlee V. Moses
Kaposi Sarcoma Herpesvirus Induces Ho-1 During De Novo Infection Of Endothelial Cells Via Viral Mirna-Dependent And -Independent Mechanisms, Sara Botto, Jennifer Totonchy, Jean K. Gustin, Ashlee V. Moses
Pharmacy Faculty Articles and Research
Kaposi sarcoma (KS) herpesvirus (KSHV) infection of endothelial cells (EC) is associated with strong induction of heme oxygenase-1 (HO-1), a stress-inducible host gene that encodes the rate-limiting enzyme responsible for heme catabolism. KS is an angioproliferative tumor characterized by the proliferation of KSHV-infected spindle cells, and HO-1 is highly expressed in such cells. HO-1 converts the pro-oxidant, proinflammatory heme molecule into metabolites with antioxidant, antiinflammatory, and proliferative activities. Previously published work has shown that KSHV-infected EC in vitro proliferate in response to free heme in a HO-1-dependent manner, thus implicating virus-enhanced HO-1 activity in KS tumorigenesis. The present study investigated …
Kshv Infection Of Endothelial Cells Manipulates Cxcr7-Mediated Signaling: Implications For Kaposi’S Sarcoma Progression And Intervention, Jennifer Totonchy, Lisa Clepper, Janet Douglas, Liron Pantanowitz, Klaus Fruh, Ashlee V. Moses
Kshv Infection Of Endothelial Cells Manipulates Cxcr7-Mediated Signaling: Implications For Kaposi’S Sarcoma Progression And Intervention, Jennifer Totonchy, Lisa Clepper, Janet Douglas, Liron Pantanowitz, Klaus Fruh, Ashlee V. Moses
Pharmacy Faculty Articles and Research
"CXCR7 was recently characterized as an alternative receptor for the chemokine CXCL12/SDF-1, previously thought to bind and signal exclusively through CXCR4.We recently identified CXCR7 as a key cellular factor in the endothelial cell (EC) dysfunction associated with KSHV infection. CXCL12 signaling is critically associated with tumor growth, angiogenesis and metastasis in several diverse tumors and is one of the most studied chemokine/chemokine receptor interactions in cancer systems. The tumorigenic activity of the CXCL12 signaling axis offers an attractive target for therapeutic intervention in multiple cancers including Kaposi’s Sarcoma (KS). However, most of the research to date was based on the …