scholarly journals Control of Cytokines in Latent Cytomegalovirus Infection

Pathogens ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 858
Author(s):  
Pearley Chinta ◽  
Erica C. Garcia ◽  
Kiran Hina Tajuddin ◽  
Naomi Akhidenor ◽  
Allyson Davis ◽  
...  
Keyword(s):  
Latent Infection ◽  
Cell Types ◽  
Cytokine Signaling ◽  
Host Immune System ◽  
Myeloid Progenitor ◽  
Wide Range ◽  
Latently Infected ◽  
Myeloid Progenitor Cells ◽  
Infected Cells

Human cytomegalovirus (HCMV) has evolved a number of mechanisms for long-term co-existence within its host. HCMV infects a wide range of cell types, including fibroblasts, epithelial cells, monocytes, macrophages, dendritic cells, and myeloid progenitor cells. Lytic infection, with the production of infectious progeny virions, occurs in differentiated cell types, while undifferentiated myeloid precursor cells are the primary site of latent infection. The outcome of HCMV infection depends partly on the cell type and differentiation state but is also influenced by the composition of the immune environment. In this review, we discuss the role of early interactions between HCMV and the host immune system, particularly cytokine and chemokine networks, that facilitate the establishment of lifelong latent infection. A better understanding of these cytokine signaling pathways could lead to novel therapeutic targets that might prevent latency or eradicate latently infected cells.

scholarly journals Latently KSHV-Infected Cells Promote Further Establishment of Latency upon Superinfection with KSHV

2021 ◽  
Vol 22 (21) ◽  
pp. 11994
Author(s):  
Chen Gam ze Letova ◽  
Inna Kalt ◽  
Meir Shamay ◽  
Ronit Sarid
Keyword(s):  
Latent Infection ◽  
Fluorescent Proteins ◽  
Cell Types ◽  
Lytic Cycle ◽  
Viral Reservoir ◽  
Virus Spread ◽  
Viral Genomes ◽  
Latently Infected ◽  
Infected Cells

Kaposi’s sarcoma-associated herpesvirus (KSHV) is a cancer-related virus which engages in two forms of infection: latent and lytic. Latent infection allows the virus to establish long-term persistent infection, whereas the lytic cycle is needed for the maintenance of the viral reservoir and for virus spread. By using recombinant KSHV viruses encoding mNeonGreen and mCherry fluorescent proteins, we show that various cell types that are latently-infected with KSHV can be superinfected, and that the new incoming viruses establish latent infection. Moreover, we show that latency establishment is enhanced in superinfected cells compared to primary infected ones. Further analysis revealed that cells that ectopically express the major latency protein of KSHV, LANA-1, prior to and during infection exhibit enhanced establishment of latency, but not cells expressing LANA-1 fragments. This observation supports the notion that the expression level of LANA-1 following infection determines the efficiency of latency establishment and avoids loss of viral genomes. These findings imply that a host can be infected with more than a single viral genome and that superinfection may support the maintenance of long-term latency.

scholarly journals Latent Antigen Vaccination in a Model Gammaherpesvirus Infection

2001 ◽  
Vol 75 (17) ◽  
pp. 8283-8288 ◽  
Author(s):  
Edward J. Usherwood ◽  
Kimberley A. Ward ◽  
Marcia A. Blackman ◽  
James P. Stewart ◽  
David L. Woodland
Keyword(s):  
Latent Infection ◽  
Model Systems ◽  
Murine Gammaherpesvirus ◽  
Latently Infected ◽  
Associated Proteins ◽  
Infected Cells ◽  
The Impact ◽  
First Time

ABSTRACT Vaccines that can reduce the load of latent gammaherpesvirus infections are eagerly sought. One attractive strategy is vaccination against latency-associated proteins, which may increase the efficiency with which T cells recognize and eliminate latently infected cells. However, due to the lack of tractable animal model systems, the effect of latent-antigen vaccination on gammaherpesvirus latency is not known. Here we use the murine gammaherpesvirus model to investigate the impact of vaccination with the latency-associated M2 antigen. As expected, vaccination had no effect on the acute lung infection. However, there was a significant reduction in the load of latently infected cells in the initial stages of the latent infection, when M2 is expressed. These data show for the first time that latent-antigen vaccination can reduce the level of latency in vivo and suggest that vaccination strategies involving other latent antigens may ultimately be successfully used to reduce the long-term latent infection.

scholarly journals COVID-19-related anosmia is associated with viral persistence and inflammation in human olfactory epithelium and brain infection in hamsters

2021 ◽  
pp. eabf8396
Author(s):  
Guilherme Dias de Melo ◽  
Françoise Lazarini ◽  
Sylvain Levallois ◽  
Charlotte Hautefort ◽  
Vincent Michel ◽  
...  
Keyword(s):  
Olfactory Epithelium ◽  
Cell Types ◽  
Brain Infection ◽  
Olfactory Neuroepithelium ◽  
Optimal Medical Management ◽  
Infected Cells ◽  
Multiple Cell ◽  
Lung Pathogenesis ◽  
Taste Dysfunction

Whereas recent investigations have revealed viral, inflammatory and vascular factors involved in SARS-CoV-2 lung pathogenesis, the pathophysiology of neurological disorders in COVID-19 remains poorly understood. Olfactory and taste dysfunction are common in COVID-19, especially in mildly symptomatic patients. Here, we conducted a virologic, molecular, and cellular study of the olfactory neuroepithelium of seven patients with COVID-19 presenting with acute loss of smell. We report evidence that the olfactory neuroepithelium may be a major site of SARS-CoV2 infection with multiple cell types, including olfactory sensory neurons, support cells, and immune cells, becoming infected. SARS-CoV-2 replication in the olfactory neuroepithelium was associated with local inflammation. Furthermore, we showed that SARS-CoV-2 induced acute anosmia and ageusia in golden Syrian hamsters, lasting as long as the virus remained in the olfactory epithelium and the olfactory bulb. Finally, olfactory mucosa sampling from patients showing long-term persistence of COVID-19-associated anosmia revealed the presence of virus transcripts and of SARS-CoV-2-infected cells, together with protracted inflammation. SARS-CoV-2 persistence and associated inflammation in the olfactory neuroepithelium may account for prolonged or relapsing symptoms of COVID-19, such as loss of smell, which should be considered for optimal medical management of this disease.

scholarly journals A Zebrafish Model of Myelodysplastic Syndrome Produced throughtet2Genomic Editing

2014 ◽  
Vol 35 (5) ◽  
pp. 789-804 ◽  
Author(s):  
Evisa Gjini ◽  
Marc R. Mansour ◽  
Jeffry D. Sander ◽  
Nadine Moritz ◽  
Ashley T. Nguyen ◽  
...  
Keyword(s):  
Myelodysplastic Syndrome ◽  
Catalytic Domain ◽  
Specific Activity ◽  
Cpg Islands ◽  
Hematopoietic Cells ◽  
Cell Types ◽  
Loss Of Function ◽  
Zebrafish Model ◽  
Myeloid Progenitor ◽  
Myeloid Progenitor Cells

The ten-eleven translocation 2 gene (TET2) encodes a member of the TET family of DNA methylcytosine oxidases that converts 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) to initiate the demethylation of DNA within genomic CpG islands. Somatic loss-of-function mutations ofTET2are frequently observed in human myelodysplastic syndrome (MDS), which is a clonal malignancy characterized by dysplastic changes of developing blood cell progenitors, leading to ineffective hematopoiesis. We used genome-editing technology to disrupt the zebrafish Tet2 catalytic domain.tet2m/m(homozygous for the mutation) zebrafish exhibited normal embryonic and larval hematopoiesis but developed progressive clonal myelodysplasia as they aged, culminating in myelodysplastic syndromes (MDS) at 24 months of age, with dysplasia of myeloid progenitor cells and anemia with abnormal circulating erythrocytes. The resultanttet2m/mmutant zebrafish lines show decreased levels of 5hmC in hematopoietic cells of the kidney marrow but not in other cell types, most likely reflecting the ability of other Tet family members to provide this enzymatic activity in nonhematopoietic tissues but not in hematopoietic cells.tet2m/mzebrafish are viable and fertile, providing an ideal model to dissect altered pathways in hematopoietic cells and, for small-molecule screens in embryos, to identify compounds with specific activity againsttet2mutant cells.

scholarly journals Bone marrow stem and progenitor cell contribution to neovasculogenesis is dependent on model system with SDF-1 as a permissive trigger

Blood ◽  
2009 ◽  
Vol 114 (19) ◽  
pp. 4310-4319 ◽  
Author(s):  
Gerard J. Madlambayan ◽  
Jason M. Butler ◽  
Koji Hosaka ◽  
Marda Jorgensen ◽  
Dongtao Fu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Neutralizing Antibodies ◽  
Model Systems ◽  
Experimental Methodology ◽  
Specific Expression ◽  
Hematopoietic Stem ◽  
Lung Carcinoma Cells ◽  
Myeloid Progenitor ◽  
Myeloid Progenitor Cells

Abstract Adult bone marrow (BM) contributes to neovascularization in some but not all settings, and reasons for these discordant results have remained unexplored. We conducted novel comparative studies in which multiple neovascularization models were established in single mice to reduce variations in experimental methodology. In different combinations, BM contribution was detected in ischemic retinas and, to a lesser extent, Lewis lung carcinoma cells, whereas B16 melanomas showed little to no BM contribution. Using this spectrum of BM contribution, we demonstrate the necessity for site-specific expression of stromal-derived factor-1α (SDF-1α) and its mobilizing effects on BM. Blocking SDF-1α activity with neutralizing antibodies abrogated BM-derived neovascularization in lung cancer and retinopathy. Furthermore, secondary transplantation of single hematopoietic stem cells (HSCs) showed that HSCs are a long-term source of neovasculogenesis and that CD133+CXCR4+ myeloid progenitor cells directly participate in new blood vessel formation in response to SDF-1α. The varied BM contribution seen in different model systems is suggestive of redundant mechanisms governing postnatal neovasculogenesis and provides an explanation for contradictory results observed in the field.

Noncoding RNAs and RNA Editing in Brain Development, Functional Diversification, and Neurological Disease

2007 ◽  
Vol 87 (3) ◽  
pp. 799-823 ◽  
Author(s):  
Mark F. Mehler ◽  
John S. Mattick
Keyword(s):  
Nervous System ◽  
Rna Editing ◽  
Neurological Diseases ◽  
Cell Types ◽  
State Transitions ◽  
Long Term Memory ◽  
Protein Coding ◽  
Continuous State ◽  
Wide Range

The progressive maturation and functional plasticity of the nervous system in health and disease involve a dynamic interplay between the transcriptome and the environment. There is a growing awareness that the previously unexplored molecular and functional interface mediating these complex gene-environmental interactions, particularly in brain, may encompass a sophisticated RNA regulatory network involving the twin processes of RNA editing and multifaceted actions of numerous subclasses of non-protein-coding RNAs. The mature nervous system encompasses a wide range of cell types and interconnections. Long-term changes in the strength of synaptic connections are thought to underlie memory retrieval, formation, stabilization, and effector functions. The evolving nervous system involves numerous developmental transitions, such as neurulation, neural tube patterning, neural stem cell expansion and maintenance, lineage elaboration, differentiation, axonal path finding, and synaptogenesis. Although the molecular bases for these processes are largely unknown, RNA-based epigenetic mechanisms appear to be essential for orchestrating these precise and versatile biological phenomena and in defining the etiology of a spectrum of neurological diseases. The concerted modulation of RNA editing and the selective expression of non-protein-coding RNAs during seminal as well as continuous state transitions may comprise the plastic molecular code needed to couple the intrinsic malleability of neural network connections to evolving environmental influences to establish diverse forms of short- and long-term memory, context-specific behavioral responses, and sophisticated cognitive capacities.

scholarly journals The Potential Contribution of Caveolin 1 to HIV Latent Infection

Pathogens ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 896
Author(s):  
Bikash Sahay ◽  
Ayalew Mergia
Keyword(s):  
Latent Infection ◽  
Cell Types ◽  
Potential Contribution ◽  
Resting Cells ◽  
Hiv Replication ◽  
Functional Protein ◽  
Caveolin 1 ◽  
Hiv Transcription ◽  
Latently Infected

Combinatorial antiretroviral therapy (cART) suppresses HIV replication to undetectable levels and has been effective in prolonging the lives of HIV infected individuals. However, cART is not capable of eradicating HIV from infected individuals mainly due to HIV’s persistence in small reservoirs of latently infected resting cells. Latent infection occurs when the HIV-1 provirus becomes transcriptionally inactive and several mechanisms that contribute to the silencing of HIV transcription have been described. Despite these advances, latent infection remains a major hurdle to cure HIV infected individuals. Therefore, there is a need for more understanding of novel mechanisms that are associated with latent infection to purge HIV from infected individuals thoroughly. Caveolin 1(Cav-1) is a multifaceted functional protein expressed in many cell types. The expression of Cav-1 in lymphocytes has been controversial. Recent evidence, however, convincingly established the expression of Cav-1 in lymphocytes. In lieu of this finding, the current review examines the potential role of Cav-1 in HIV latent infection and provides a perspective that helps uncover new insights to understand HIV latent infection.

Exploring HIV latency using transcription profiling

2017 ◽  
Vol 38 (3) ◽  
pp. 137
Author(s):  
Sushama Telwatte ◽  
Steven A Yukl
Keyword(s):  
Transcriptional Profiling ◽  
Cell Types ◽  
Hiv Latency ◽  
Dna Viruses ◽  
Major Barrier ◽  
Hiv Transcription ◽  
Latently Infected ◽  
Infected Cells ◽  
Mechanisms Of Persistence

The major barrier to a cure for HIV is the existence of reservoirs consisting predominantly of latently infected CD4+ T cells, which do not produce virus constitutively but can be induced to produce infectious virus on activation. HIV latency research has largely focused on peripheral blood, yet most HIV-infected cells reside in tissues, especially the gut, where differences in drug penetration, cell types, and immune responses may impact mechanisms of persistence. Exploring the differences between the gut and the blood in transcriptional blocks may reveal fundamental insights into mechanisms that contribute to HIV latency. Our novel transcriptional profiling assays enable us to determine where blocks to HIV transcription occur in various tissues and the magnitude of their contribution. These assays could also be adapted to investigate latency established by other retroviridae or even DNA viruses such as herpesviridae with a view to pinpointing mechanisms underlying latency in vivo and ultimately contribute to designing a cure.

scholarly journals A population shift between two heritable cell types of the pathogenCandida albicansis based both on switching and selective proliferation

2019 ◽  
Vol 116 (52) ◽  
pp. 26918-26924 ◽  
Author(s):  
Chiraj K. Dalal ◽  
Ignacio A. Zuleta ◽  
Matthew B. Lohse ◽  
Rebecca E. Zordan ◽  
Hana El-Samad ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Fungal Pathogen ◽  
Cell Types ◽  
White Cell ◽  
Switching Frequency ◽  
Flow Cytometry Assay ◽  
Daughter Cells ◽  
Distinct Cell ◽  
Wide Range

Differentiated cell types often retain their characteristics through many rounds of cell division. A simple example is found inCandida albicans, a member of the human microbiota and also the most prevalent fungal pathogen of humans; here, two distinct cell types (white and opaque) exist, and each one retains its specialized properties across many cell divisions. Switching between the two cell types is rare in standard laboratory medium (2% glucose) but can be increased by signals in the environment, for example, certain sugars. When these signals are removed, switching ceases and cells remain in their present state, which is faithfully passed on through many generations of daughter cells. Here, using an automated flow cytometry assay to monitor white–opaque switching over 96 different sugar concentrations, we observed a wide range of opaque-to-white switching that varied continuously across different sugar compositions of the medium. By also measuring white cell proliferation rates under each condition, we found that both opaque-to-white switching and selective white cell proliferation are required for entire populations to shift from opaque to white. Moreover, the switching frequency correlates with the preference of the resulting cell type for the growth medium; that is, the switching is adjusted to increase in environments that favor white cell proliferation. The widely adjustable, all-or-none nature of the switch, combined with the long-term heritability of each state, is distinct from conventional forms of gene regulation, and we propose that it represents a strategy used byC. albicansto efficiently colonize different niches of its human host.

scholarly journals Factor XIII Subunit A in the Skin: Applications in Diagnosis and Treatment

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Lilla Paragh ◽  
Daniel Törőcsik
Keyword(s):  
Factor Xiii ◽  
Potential Role ◽  
Cell Types ◽  
Subunit A ◽  
Therapeutic Implications ◽  
Inflammatory Conditions ◽  
Dermal Cell ◽  
Wide Range

The role of factor XIII subunit A (FXIII-A) is not restricted to hemostasis. FXIII-A is also present intracellularly in several human cells and serves as a diagnostic marker in a wide range of dermatological diseases from inflammatory conditions to malignancies. In this review, we provide a guide on the still controversial interpretation of dermal cell types expressing FXIII-A and assess the previously described mechanisms behind their accumulation under physiological and pathological conditions of the human skin. We summarize the intracellular functions of FXIII-A as well as its possible sources in the extracellular space of the dermis with a focus on its relevance to skin homeostasis and disease pathogenesis. Finally, the potential role of FXIII-A in wound healing, as a field with long-term therapeutic implications, is also discussed.

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