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 COVID-19-associated olfactory dysfunction reveals SARS-CoV-2 neuroinvasion and persistence in the olfactory system

2020 ◽  
Author(s):  
Guilherme Dias De Melo ◽  
Françoise Lazarini ◽  
Sylvain Levallois ◽  
Charlotte Hautefort ◽  
Vincent Michel ◽  
...  
Keyword(s):  
Olfactory Epithelium ◽  
Neurological Disorders ◽  
Olfactory System ◽  
Cell Types ◽  
Infection Site ◽  
Optimal Medical Management ◽  
Infected Cells ◽  
Multiple Cell ◽  
Lung Pathogenesis ◽  
Taste Dysfunction

AbstractWhile 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. Yet, olfactory and taste dysfunction are rather common in COVID-19, especially in pauci-symptomatic patients which constitutes the most frequent clinical manifestation of the infection. We conducted a virologic, molecular, and cellular study of the olfactory system from COVID-19 patients presenting acute loss of smell, and report evidence that the olfactory epithelium represents a highly significant infection site where multiple cell types, including olfactory sensory neurons, support cells and immune cells, are infected. Viral replication in the olfactory epithelium is associated with local inflammation. Furthermore, we show that SARS-CoV-2 induces acute anosmia and ageusia in golden Syrian hamsters, both lasting as long as the virus remains in the olfactory epithelium and the olfactory bulb. Finally, olfactory mucosa sampling in COVID-19 patients presenting with persistent loss of smell reveals the presence of virus transcripts and of SARS-CoV-2-infected cells, together with protracted inflammation. Viral persistence in the olfactory epithelium therefore provides a potential mechanism for prolonged or relapsing symptoms of COVID-19, such as loss of smell, which should be considered for optimal medical management and future therapeutic strategies.

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 Analysis of multispectral imaging with the AstroPath platform informs efficacy of PD-1 blockade

Science ◽  
2021 ◽  
Vol 372 (6547) ◽  
pp. eaba2609
Author(s):  
Sneha Berry ◽  
Nicolas A. Giraldo ◽  
Benjamin F. Green ◽  
Tricia R. Cottrell ◽  
Julie E. Stein ◽  
...  
Keyword(s):  
Multispectral Imaging ◽  
Expression Patterns ◽  
Cell Types ◽  
Term Survival ◽  
Multiple Parameters ◽  
Tissue Sections ◽  
Programmed Cell Death 1 ◽  
Multiple Cell ◽  
Independent Cohort

Next-generation tissue-based biomarkers for immunotherapy will likely include the simultaneous analysis of multiple cell types and their spatial interactions, as well as distinct expression patterns of immunoregulatory molecules. Here, we introduce a comprehensive platform for multispectral imaging and mapping of multiple parameters in tumor tissue sections with high-fidelity single-cell resolution. Image analysis and data handling components were drawn from the field of astronomy. Using this “AstroPath” whole-slide platform and only six markers, we identified key features in pretreatment melanoma specimens that predicted response to anti–programmed cell death-1 (PD-1)–based therapy, including CD163+PD-L1– myeloid cells and CD8+FoxP3+PD-1low/mid T cells. These features were combined to stratify long-term survival after anti–PD-1 blockade. This signature was validated in an independent cohort of patients with melanoma from a different institution.

scholarly journals A New Organotypic Culture of Adipose Tissue Fragments Maintains Viable Mature Adipocytes for a Long Term, Together with Development of Immature Adipocytes and Mesenchymal Stem Cell-Like Cells

Endocrinology ◽  
2008 ◽  
Vol 149 (10) ◽  
pp. 4794-4798 ◽  
Author(s):  
Emiko Sonoda ◽  
Shigehisa Aoki ◽  
Kazuyoshi Uchihashi ◽  
Hidenobu Soejima ◽  
Sachiko Kanaji ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Organotypic Culture ◽  
Three Dimensional ◽  
Collagen Gel ◽  
Cell Types ◽  
Ppar Γ ◽  
Tnf Α ◽  
Multiple Cell ◽  
Related Agent

Adipose tissue that consists of mature and immature adipocytes is suggested to contain mesenchymal stem cells (MSCs), but a culture system for analyzing their cell types within the tissue has not been established. Here we show that three-dimensional collagen gel culture of rat sc adipose tissue fragments maintained viable mature adipocytes for a long term, producing immature adipocytes and MSC-like cells from the fragments, using immunohistochemistry, ELISA, and real time RT-PCR. Bromodeoxyuridine uptake of mature adipocytes was detected. Adiponectin and leptin, and adipocyte-specific genes of adiponectin, leptin, and PPAR-γ were detected in culture assembly, whereas the lipogenesis factor insulin (20 mU/ml) and inflammation-related agent TNF-α (2 nm) increased and decreased, respectively, all of their displays. Both spindle-shaped cell types with oil red O-positive lipid droplets and those with expression of MSC markers (CD105 and CD44) developed around the fragments. The data indicate that adipose tissue-organotypic culture retains unilocular structure, proliferative ability, and some functions of mature adipocytes, generating both immature adipocytes and CD105+/CD44+ MSC-like cells. This suggests that our method will open up a new way for studying both multiple cell types within adipose tissue and the cell-based mechanisms of obesity and metabolic syndrome.

scholarly journals Evaluation of Antimicrosporidian Activity of Plant Extracts on Nosema ceranae

2016 ◽  
Vol 60 (2) ◽  
pp. 167-178 ◽  
Author(s):  
Jeong Hwa Kim ◽  
Jin Kyu Park ◽  
Jae Kwon Lee
Keyword(s):  
Apis Mellifera ◽  
Cell Types ◽  
Mechanisms Of Action ◽  
Nosema Ceranae ◽  
Nosema Apis ◽  
Microsporidian Species ◽  
Infected Cells ◽  
Multiple Cell ◽  
Artemisia Dubia ◽  
Toxic Concentrations

Abstract Nosemosis is one of the most common protozoan diseases of adult bees (Apis mellifera). Nosemosis is caused by two species of microsporidia; Nosema apis and Nosema ceranae. Nosema ceranae is potentially more dangerous because it has the ability to infect multiple cell types, and it is now the predominant microsporidian species in A. mellifera. In this study, we identified two anti-nosemosis plants, Aster scaber and Artemisia dubia, which reduced the spore development of N. ceranae in spore-infected cells. The most important aspect of our results was that our treatment was effective at non-toxic concentrations. Anti-nosemosis activities of both plants were revealed in honey bee experiments. Specifically, a mixed extract of both A. scaber and A. dubia showed stronger activity than treatment with each single extract alone. Although the mechanisms of action of A. scaber and A. dubia against N. ceranae are still unclear, our results suggest new medicaments and therapeutic methods to control N. ceranae infection.

scholarly journals Improved Isolation of Mesenchymal Stem Cells Based on Interactions between N-Acetylglucosamine-Bearing Polymers and Cell-Surface Vimentin

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Hirohiko Ise ◽  
Kumiko Matsunaga ◽  
Marie Shinohara ◽  
Yasuyuki Sakai
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Tissue Culture ◽  
Mesenchymal Stem Cells ◽  
Bone Marrow Cells ◽  
Cell Types ◽  
Binding Activity ◽  
Isolation System ◽  
Multiple Cell

Mesenchymal stem cells (MSCs) in bone marrow and adipose tissues are expected to be effective tools for regenerative medicine to treat various diseases. To obtain MSCs that possess both high differentiation and tissue regenerative potential, it is necessary to establish an isolation system that does not require long-term culture. It has previously been reported that the cytoskeletal protein vimentin, expressed on the surfaces of multiple cell types, possesses N-acetylglucosamine- (GlcNAc-) binding activity. Therefore, we tried to exploit this interaction to efficiently isolate MSCs from rat bone marrow cells using GlcNAc-bearing polymer-coated dishes. Cells isolated by this method were identified as MSCs because they were CD34-, CD45-, and CD11b/c-negative and CD90-, CD29-, CD44-, CD54-, CD73-, and CD105-positive. Osteoblast, adipocyte, and chondrocyte differentiation was observed in these cells. In total, yields of rat MSCs were threefold to fourfold higher using GlcNAc-bearing polymer-coated dishes than yields using conventional tissue-culture dishes. Interestingly, MSCs isolated with GlcNAc-bearing polymer-coated dishes strongly expressed CD106, whereas those isolated with conventional tissue-culture dishes had low CD106 expression. Moreover, senescence-associated β-galactosidase activity in MSCs from GlcNAc-bearing polymer-coated dishes was lower than that in MSCs from tissue-culture dishes. These results establish an improved isolation method for high-quality MSCs.

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 Anosmia in COVID-19: Underlying Mechanisms and Assessment of an Olfactory Route to Brain Infection

2020 ◽  
pp. 107385842095690 ◽  
Author(s):  
Rafal Butowt ◽  
Christopher S. von Bartheld
Keyword(s):  
Olfactory Epithelium ◽  
Molecular Mechanisms ◽  
Large Fraction ◽  
Current Evidence ◽  
The Novel ◽  
Brain Infection ◽  
Sustentacular Cells ◽  
Underlying Mechanisms ◽  
Novel Coronavirus ◽  
Taste Dysfunction

In recent months it has emerged that the novel coronavirus—responsible for the COVID-19 pandemic—causes reduction of smell and taste in a large fraction of patients. The chemosensory deficits are often the earliest, and sometimes the only signs in otherwise asymptomatic carriers of the SARS-CoV-2 virus. The reasons for the surprisingly early and specific chemosensory dysfunction in COVID-19 are now beginning to be elucidated. In this hypothesis review, we discuss implications of the recent finding that the prevalence of smell and taste dysfunction in COVID-19 patients differs between populations, possibly because of differences in the spike protein of different virus strains or because of differences in the host proteins that enable virus entry, thus modifying infectivity. We review recent progress in defining underlying cellular and molecular mechanisms of the virus-induced anosmia, with a focus on the emerging crucial role of sustentacular cells in the olfactory epithelium. We critically examine the current evidence whether and how the SARS-CoV-2 virus can follow a route from the olfactory epithelium in the nose to the brain to achieve brain infection, and we discuss the prospects for using the smell and taste dysfunctions seen in COVID-19 as an early and rapid diagnostic screening tool.

scholarly journals Real-time high-speed mobility management

2021 ◽  
Vol 24 (3) ◽  
pp. 1534
Author(s):  
Ahmed Abdelsalam Abuelgasim ◽  
Mohamed Khalafalla Hassan ◽  
Mutaz Hamed Khairi ◽  
Muhammad Nadzir Marsono ◽  
Kamaludin Mohamad Yusof
Keyword(s):  
High Speed ◽  
Real Life ◽  
Cell Types ◽  
Network Coverage ◽  
Measurement Monitoring ◽  
Term Evolution ◽  
Mobility System ◽  
Multiple Cell ◽  
Better Than

High-speed mobility system has now become a serious concern for mobile operators due to the large frameworks of a heterogeneous network made up of multiple cell types and different frequency bands. Handover (HO) is conducted in a real-life scenario when the user equipment (UE) moves from one network coverage to another by performing proper measurement with high speed. HO breakdown and call loss are observed due to a high speed; thus, high-speed mobility system needs improvement by using the UE speed as one of the key measurement monitoring criteria for the long-term evolution (LTE) network. Vendor consultation has been considered in this paper in addition to real drive test measurement in highways. Results have shown that velocity has a direct impact on the handover quality and overall timing. Results also demonstrate that 120 km/h measurement is better than 140 km/h as UE speed.

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