Human cytomegalovirus (HCMV) is a betaherpesvirus that can cause severe birth defects including vision and hearing loss, microcephaly, seizures. Currently, no approved treatment options exist for in utero infections. Here, we aimed to determine the impact of HCMV infection on transcriptome developing neurons an organoid model system. Cell populations isolated from organoids based marker transcriptomes were defined. We uncovered downregulation key cortical, neurodevelopmental, functional gene...

Human cytomegalovirus (HCMV) is a highly prevalent viral pathogen that can cause serious neurological deficits in infants experiencing an

ABSTRACT Human cytomegalovirus (HCMV) infection reprograms metabolism, including lipid synthesis. While several metabolite-related pathways have been demonstrated to altered activity in infected cells, the alteration of lipid-related by HCMV has not examined beyond fatty acid synthesis and elongation. In this study, we addressed lack understanding focusing on phosphatidylcholine (PC), a class lipids previously showed is increased human foreskin fibroblasts. Here, found that increases...

Some viruses, including human cytomegalovirus (HCMV), induce the synthesis of fatty acids and lipids to ensure that lipid environment infected cells supports virus replication. HCMV infection broadly reprograms metabolism central carbon provides metabolites required for anabolic nucleotides, proteins, while also meeting energy demands placed on cells. While increases levels most very long chain (VLCFA), we found erucic acid (EA), a C22:1 monounsaturated VLCFA, are reduced. Treating with EA...

JMJD1C, a member of the lysine demethylase 3 family, is aberrantly expressed in mixed lineage leukemia (MLL) gene-rearranged (MLLr) leukemias. We have shown previously that JMJD1C required for self-renewal acute myeloid (AML) stem cells (LSCs) but not normal hematopoietic cells. However, domains within promote LSC are unknown. Here, we used clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein-9 nuclease (Cas9) negative-selection screening and...

Nitric oxide is a versatile and critical effector molecule that can modulate many cellular functions. Although recognized as regulator of infections, the inhibitory mechanism nitric against human cytomegalovirus (HCMV) replication remains elusive. We demonstrate attenuates viral by interfering with HCMV-mediated modulation several processes. exposure reduced HCMV genome synthesis infectious progeny cell-type-dependent differences observed. Mitochondrial respiration was severely in both...

Human cytomegalovirus (HCMV) is the leading cause of virus-mediated congenital birth defects. Congenitally infected infants can have a variety symptoms manifesting within central nervous system.

Human cytomegalovirus (HCMV) is a major cause of illness in immunocompromised individuals. The HCMV lytic cycle contributes to the clinical manifestations infection. occurs over ∼96 h diverse cell types and consists viral DNA (vDNA) genome replication temporally distinct expression hundreds proteins. Given its complexity, understanding this elaborate system can be facilitated by introduction mechanistic computational modeling temporal relationships. Therefore, we developed multiplicity...

ABSTRACT Human cytomegalovirus (HCMV) is a beta herpesvirus that causes severe congenital birth defects including microcephaly, vision loss, and hearing loss. Entry of HCMV into human cells determined by the composition glycoproteins in viral particles influenced source virus. We have previously shown infection stem cell-derived cerebral organoids significant downregulation critical neurodevelopmental genes, but mechanism entry neural tissues not well known. Here, we evaluated efficiency...

Human cytomegalovirus (HCMV) is a highly prevalent viral pathogen that typically presents asymptomatically in healthy individuals despite lifelong latency. However, 10-15% of congenital cases, this beta-herpesvirus demonstrates direct effects on the central nervous system, including microcephaly, cognitive/learning delays, and hearing deficits. HCMV has been widely shown to infect neural progenitor cells, but permissiveness fully differentiated neurons controversial chronically understudied,...

The broad tissue distribution and cell tropism of human cytomegalovirus indicates that the virus successfully replicates in tissues with various nutrient environments. HCMV requires reprograms central carbon metabolism for viral replication. However, many studies focus on reprogramming high conditions do not recapitulate physiological environments body. In this study, we investigate how when nutrients are suboptimal. We limited glucose following infection to determine supports replication...

ABSTRACT Human cytomegalovirus (HCMV) is a prevalent betaherpesvirus, and infection can lead to range of symptomatology from mononucleosis sepsis in immunocompromised individuals. HCMV also the leading viral cause congenital birth defects. Lytic replication supported by many cell types with different kinetics efficiencies plethora pathologies. The goal these studies was elucidate for viruses produced on upon epithelial cells combining experimental approaches data-driven computational...

Viruses with broad tissue distribution and cell tropism successfully replicate in various nutrient environments the body. Several viruses reprogram metabolism for viral replication. However, many studies focus on metabolic reprogramming nutrient-rich conditions that do not recapitulate physiological Here, we investigated how may when a metabolite thought to be essential replication is limited. We use human cytomegalovirus infection glucose-free as model determine glucose supports virus...

Abstract Human cytomegalovirus (HCMV) is a beta herpesvirus that, upon congenital infection, can cause severe birth defects including vision and hearing loss, microcephaly, seizures. Currently, no approved treatment options exist for in utero infections. We previously demonstrated that HCMV infection decreases calcium signaling responses alters neuronal differentiation induced pluripotent stem cell (iPSC) derived neural progenitor cells (NPCs). Here we aimed to determine the impact of on...

Clinical manifestations of human cytomegalovirus (HCMV) infection, a major cause morbidity and mortality in the immunocompromised, are associated with lytic replication cycle. Lytic occurs over 96 hrs is marked by viral DNA (vDNA) synthesis expression proteins, latter which can be generalized into distinct temporal classifications. Given complexity cycle, mathematical modeling used to probe this elaborate system. Recently, has been study early cycle transition between latent cycles. To date,...

ABSTRACT Human cytomegalovirus (HCMV) is a beta herpesvirus that causes severe congenital birth defects including microcephaly, vision loss, and hearing loss. Infection of cerebral organoids with HCMV significant downregulation genes involved in critical neurodevelopmental pathways. The precise features the infection causing this dysregulation remain unknown. Entry into human cells determined by composition glycoproteins viral particles, which influenced source virus. This includes trimer...

Abstract Human cytomegalovirus (HCMV) is a prevalent betaherpesvirus that asymptomatic in healthy individuals but can cause serious disease immunocompromised patients. HCMV also the leading of viral-mediated birth defects. Many these defects manifest within central nervous system and include microcephaly, sensorineural hearing loss, cognitive developmental delays. Nitric oxide critical effector molecule produced as component innate immune response during infection. Using 3-dimensional...

Human cytomegalovirus (HCMV) is a beta herpesvirus that, upon congenital infection, can cause severe birth defects including vision and hearing loss, microcephaly, seizures. Currently, no approved treatment options exist for in utero infections. We previously demonstrated that HCMV infection decreases calcium signaling responses alters neuronal differentiation induced pluripotent stem cell (iPSC) derived neural progenitor cells (NPCs). Here we aimed to determine the impact of on...