The replacement histone H2A.Z is variously reported as being linked to gene expression and preventing the spread of heterochromatin in yeast, or concentrated at mammals. To resolve this apparent dichotomy, affinity-purified antibodies against N-terminal region H2A.Z, both a triacetylated non-acetylated state, are used native chromatin immmuno-precipitation experiments with mononucleosomes from three chicken cell types. hyperacetylated species concentrates 5′ end active genes, tissue specific...

Viruses transmit via the environmental and social interactions of their hosts. Herpesviruses have colonized mammals since earliest origins, suggesting that they exploit ancient, common pathways. Cytomegaloviruses (CMVs) are assumed to enter new hosts orally, but no site has been identified. We show by live imaging murine CMV (MCMV) infects nasally rather than both after experimental virus uptake during natural transmission. Replication-deficient virions revealed primary target as olfactory...

ABSTRACT Cytomegaloviruses (CMVs) establish chronic infections that spread from a primary entry site to secondary vascular sites, such as the spleen, and then tertiary shedding salivary glands. Human CMV (HCMV) is difficult analyze, because its precedes clinical presentation. Murine (MCMV) offers tractable model. It hypothesized peripheral sites via endothelial cells associated monocytes. However, viral luciferase imaging showed footpad-inoculated MCMV first reaching popliteal lymph nodes...

Herpesviruses have coevolved with their hosts over hundreds of millions years and exploit fundamental features biology. Cytomegaloviruses (CMVs) colonize blood-borne myeloid cells, it has been hypothesized that systemic dissemination arises from infected stem cells in bone marrow. However, poor CMV transfer by cell transplantation argues against this being the main reservoir. To identify alternative pathways for spread, we tracked murine (MCMV) colonization after mucosal entry. We show...

Cytomegaloviruses (CMVs) persistently and systemically infect the myeloid cells of immunocompetent hosts. Persistence implies immune evasion, CMVs evade CD8+ T by inhibiting MHC class I-restricted antigen presentation. Myeloid can also interact with CD4+ via II (MHC II). Human CMV (HCMV) attacks presentation pathway in vitro, but what role this evasion might play host colonization is unknown. We show that Murine (MCMV) down-regulates M78, a multi-membrane spanning viral protein captured from...

Dendritic cells (DCs) serve dual roles in cytomegalovirus infection: orchestrating antiviral immunity and acting as vehicles for viral dissemination. DC-dependent systemic spread of mouse (MCMV) is dependent on expression a G protein-coupled receptor (GPCR) homolog, encoded by M33. We performed global transcriptional profiling murine DCs infected with either wild-type MCMV or M33 mutant harboring single point mutation (R131Q; denoted M33NQY) which ablates constitutive protein-dependent...

Cytomegaloviruses (CMVs) establish chronic, systemic infections. Peripheral infection spreads via lymph nodes, which are also a focus of host defence. Thus, this is point at spread might be restricted. Subcapsular sinus macrophages (SSM) captured murine CMV (MCMV) from the afferent and poorly supported its replication. Blocking type I interferon (IFN-I) receptor (IFNAR) increased MCMV SSM fibroblastic reticular cells (FRC) lining subcapsular sinus, accelerated viral to spleen. Little splenic...

Cytomegaloviruses (CMVs) colonize blood-borne myeloid cells. Murine CMV (MCMV) spreads from the lungs via infected CD11c+ cells, consistent with an important role for dendritic cells (DC). We show here that MCMV entering olfactory epithelium, a natural transmission portal, also DC. They reached lymph nodes, entered blood high endothelial venules, and then salivary glands, driven by constitutive signaling of viral M33 G protein-coupled receptor (GPCR). Intraperitoneal infection delivered to...

The ongoing SARS-CoV-2 pandemic continues to be a major health burden globally, especially in resource-limited areas. Continued research into more effective and accessible vaccines is required reduce the of disease. Here, we use an emerging vaccine delivery system, high-density microarray patch (HD-MAP) deliver plasmid DNA (Delta 6P) encoding for spike protein. HD-MAP this resulted robust IgG responses mice against multiple domains cellular response vaccination was also measured, comparative...

Human cytomegalovirus (HCMV) colonizes blood-borne dendritic cells (DCs). They express US28, a viral G protein-coupled receptor (GPCR). In vitro functions have been described for but how it contributes to host colonization has unclear. The murine CMV (MCMV) M33 GPCR promotes DC recirculation. We show that US28 shares this function. Thus, recirculation is also available HCMV via and inhibiting protein-dependent signalling the potential reduce systemic infection. infection through infected...

CD4+ T cells are key to controlling cytomegalovirus infections. Salivary gland infection by murine (MCMV) provides a way identify mechanisms. CD11c+ dendritic (DC) disseminate MCMV the salivary glands, where they transfer acinar cells. Antiviral often considered be directly cytotoxic for expressing major histocompatibility complex class II (MHCII). However, persistently infected MHCII- and presumably inaccessible direct CD4 cell recognition. Here, we show that depletion amplified of but not...

Cytomegaloviruses (CMVs) establish persistent, systemic infections and cause disease by maternal-foetal transfer, suggesting that their dissemination is a key target for antiviral intervention. Late clinical presentation has meant human CMV (HCMV) not well understood. Murine (MCMV) provides tractable model. Whole mouse imaging of virus-expressed luciferase proved useful way to track infections. MCMV, in which the abundant lytic gene M78 was luciferase-tagged via self-cleaving peptide...

Cytomegaloviruses (CMVs) establish myeloid cell-associated viremias and persistent shedding from the salivary glands. In vitro studies with human CMV (HCMV) have implicated HCMV UL128 in epithelial tropism, but its role vivo is unknown. Here, we analyzed how a murine (MCMV) protein similar physical properties, designated MCK-2, contributes to host colonization.

Host control of mouse cytomegalovirus (MCMV) infection MHCII - salivary gland acinar cells is mediated by CD4 + T cells, but how they protect unclear. Here, we show MCMV indirectly in the gland, via IFNγ engagement with uninfected, antigen APC and recruitment NK to infected cell foci. This immune mechanism renders direct contact unnecessary may represent a host strategy overcome viral evasion.

CD4

Native chromatin IP assays were used to define changes in core histone acetylation at the lysozyme locus during developmental maturation of chicken macrophages and stimulation high-level expression by lipo-polysaccharide. In pluripotent precursors gene (Lys) is inactive there no histones gene, its promoter or upstream cis-control elements. myeloblasts, where a very low level Lys expression, H4 appears elements but not promoter: neither H3 nor H2B become significantly acetylated myeloblasts....

Human cytomegalovirus is a leading cause of congenital disease. This reflects its capacity for systemic spread. A vaccine needed, but the best viral targets are unclear. Attention has focused on virion membrane fusion complex. It 2 forms, so we need to know what each contributes host colonization. One includes glycoprotein O. We used murine cytomegalovirus, which equivalent complexes, determine importance O after mucosal infection. show that it drives local virus replication in epithelial...

G protein-coupled receptors (GPCRs) act as cell surface molecular “switches” that regulate the cellular response to environmental stimuli. All cytomegalovirus (CMV) genomes analyzed date possess GPCR homologs with phylogenetic evidence for independent gene capture events, signifying important in vivo roles.

Cytomegaloviruses (CMVs) use myeloid cells to move within their hosts. Murine CMV (MCMV) colonizes the salivary glands for long-term shedding, and reaches them via CD11c+ infected cells. A need recruit patrolling monocytes systemic spread has been proposed, based on poor gland infection in fractalkine receptor (CX3CR1)-deficient mice. We found no significant CX3CR1 dependence of infection. CCL2 viral m131/m129 chemokine homologue were also redundant acute MCMV spread, arguing against a...

Vaccination against the betaherpesvirus, human cytomegalovirus (HCMV) is a public health goal. However, HCMV has proved difficult to vaccinate against. single determinants not worked, suggesting that immunity wider antigenic profile may be required. Live attenuated vaccines provide best prospects for protection, but question remains as how balance vaccine virulence with safety. Animal models of infection insights into identifying targets virus attenuation and understanding host blocks...

Cytomegaloviruses (CMVs) transmit via chronic shedding from the salivary glands. How this relates to broad cell tropism they exhibit in vitro is unclear. Human CMV (HCMV) infection presents only after gland established. Murine (MCMV) therefore useful analyse early events. It reaches glands infected myeloid cells. Three adjacent spliced genes designated as m131/129 (MCK-2), sgg1 and sgg1.1, positional homologues of HCMV UL128/130/131 determinants, are implicated. We show that a null mutant...

Abstract Partial lipodystrophy syndromes (PL) involve selective deficiency of adipose tissue, with regional fat in the lower extremities and preservation or even excess face neck. Clinical features typical PL include severe insulin resistance, diabetes mellitus, hypertriglyceridemia non-alcoholic fatty liver disease. Apolipoprotein CIII (Apo-CIII) is elevated PL, thought to contribute high TG by inhibiting lipoprotein lipase (LPL). However, prior studies this drug patients LPL mutations...

All organisms depend on genetic diversity to cope with environmental change. Small viruses rely frequent point mutations.