We previously reported that monoclonal antibodies to protein-disulfide isomerase (PDI) and other membrane-impermeant PDI inhibitors prevented HIV-1 infection. is present at the surface of target cells reduces disulfide bonds in a model peptide attached cell membrane. Here we show soluble cleaves recombinant envelope glycoprotein gp120 bound receptor CD4 undergoes reduction by inhibitors. Concentrations prevent this inhibit cleavage surface-bound conjugate infection level entry. The entry...

Dendritic cells (DCs) contribute to human immunodeficiency virus type 1 (HIV-1) transmission and dissemination by capturing transporting infectious from the mucosa draining lymph nodes, transferring these particles CD4+ T with high efficiency. Toll-like receptor (TLR)-induced maturation of DCs enhances their ability mediate trans-infection migrate site infection. Because TLR-induced can be inhibited nuclear (NR) signaling, we hypothesized that ligand-activated NRs could repress DC-mediated...

Introduction The clinical manifestations of acute severe respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection and disease 2019 (COVID-19) suggest a dysregulation the host immune response that leads to inflammation, thrombosis, organ dysfunction. It is less clear whether these dysregulated processes persist during convalescent phase or long COVID. We sought examine effects SARS-CoV-2 on proportions classical, intermediate, nonclassical monocytes, their activation status, functional...

ABSTRACT Sexually transmitted pathogens activate HIV-1 replication and inflammatory gene expression in macrophages through engagement of Toll-like receptors (TLRs). Ligand-activated nuclear receptor (NR) transcription factors, including glucocorticoid (GR), peroxisome proliferator-activated gamma (PPARγ), liver X (LXR), are potent inhibitors TLR-induced expression. We therefore hypothesized that ligand-activated NRs repress both basal pathogen-enhanced by directly repressing ameliorating the...

Macrophages are susceptible to human immunodeficiency virus type 1 (HIV-1) infection despite abundant expression of antiviral proteins. Perhaps the most important protein is restriction factor sterile alpha motif domain and histidine/aspartic acid domain-containing (SAMHD1). We investigated role SAMHD1 its phospho-dependent regulation in context HIV-1 primary monocyte-derived macrophages ability various interferons (IFNs) pharmacologic agents modulate SAMHD1. Here we show that stimulation by...

Abstract Macrophages chronically infected with HIV-1 serve as a reservoir that contributes to persistence during antiretroviral therapy; however, the mechanisms governing establishment and maintenance of this virus have not been fully elucidated. Here, we show enters state reminiscent latency in monocyte-derived macrophages (MDMs), characterized by integrated proviral DNA decreased viral transcription. This quiescent is associated NF-κB p65, RNA polymerase II, p-TEFb recruitment promoter...

Vitamin A deficiency has been correlated with increased severity of human immunodeficiency virus type 1 (HIV-1)-associated disease. Moreover, vitamin supplementation can reduce AIDS-associated morbidity and mortality. Our group others have shown that retinoids, the bioactive metabolites A, repress HIV-1 replication in monocytic cell lines primary macrophages by blocking long-terminal-repeat (LTR)-directed transcription. Based on these studies, we hypothesize retinoids are natural repressors...

All-trans retinoic acid (RA) represses HIV-1 transcription and replication in cultured monocytic cells primary monocyte-derived macrophages. Here we examine the role of histone acetylation chromatin remodeling RA-mediated repression. RA pretreatment latently infected U1 promonocytes inhibits expression response to deacetylase (HDAC) inhibitor, trichostatin A (TSA). TSA is thought activate by inducing hyperacetylation within a regulatory nucleosome, nuc-1, positioned immediately downstream...

Macrophages are infected by HIV-1 in vivo and contribute to both viral spread pathogenesis. Recent human animal studies suggest that HIV-1-infected macrophages serve as a reservoir contributes persistence during anti-retroviral therapy. The ability of persistent reservoirs is likely influenced the local tissue microenvironment, including interactions with pathogenic commensal microbes. Here we show sexually transmitted pathogen Neisseria gonorrhoeae (GC) gut-associated microbe Escherichia...

With the changing landscape of medicine in general, and pathology particular, a greater emphasis is being placed on laboratory management as means controlling spiraling medical costs improving health-care efficiency. To meet this challenge, residency programs have begun to incorporate formal training into their curricula, using institutional curricula and/or online courses offered by professional organizations. At University Utah, its affiliated national reference laboratory, ARUP...

HIV-1 infection of myeloid cells is associated with the induction an IFN response. How manipulates and subverts response key interest for design therapeutics to improve immune function mitigate dysregulation in people living HIV. accessory genes viral fitness by altering host pathways ways that enable transmission occur without interference from We previously described changes transcriptomes infected IFN-stimulated macrophages noted transcription IFN-regulated related cell cycle processes...

All-trans-retinoic acid (RA) has been shown either to activate or repress human immunodeficiency virus type 1 (HIV-1) replication in primary monocyte-derived-macrophages (MDMs). We systematically investigated the contribution that cell donor and differences make this variability. found effect of RA was dependent. In addition, ability HIV-1 varied between different stocks. no case did affect entry integration but instead affected accumulation viral mRNAs infected cells. Despite complex...

ABSTRACT Macrophages are infected by HIV-1 in vivo and contribute to both viral spread pathogenesis. Recent human animal studies suggest that HIV-1-infected macrophages serve as a reservoir contributes persistence during anti-retroviral therapy. The ability of persistent reservoirs is likely influenced the local tissue microenvironment, including interactions with pathogenic commensal microbes. Here we show sexually transmitted pathogen Neisseria gonorrhoeae (GC) gut-associated microbe...

ABSTRACT The clinical manifestations of acute severe respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection and COVID-19 suggest a dysregulation the host immune response that leads to inflammation, thrombosis, organ dysfunction. It is less clear whether these dysregulated processes persist during convalescent phase disease or long COVID. We investigated effects SARS-CoV-2 on proportions classical, intermediate, non-classical monocytes, their activation status, functional properties...