Nuclear bodies are membrane-free nuclear substructures that are localized in the mammalian nuclear matrix region. They are multiprotein complexes that recruit other proteins to participate in various cellular activities, such as transcription, RNA splicing, epigenetic regulation, tumorigenesis and antiviral defense. It is of great significance to clarify the functions and regulatory mechanisms of nuclear bodies to probe related diseases and virus-host interactions. This review takes several nuclear bodies associated proteins as examples, summarizes the formation process, structure and functions of nuclear bodies, and focuses on their important roles in antiviral infection. It is expected to provide new insight into host antiviral mechanisms.
Animals ; Cell Nucleus ; Epigenesis, Genetic ; Intranuclear Inclusion Bodies/metabolism* ; Nuclear Proteins/metabolism*

MYH9-related disorders (MYH9RD) are autosomal-dominant disorders characterized by macrothrombocytopenia with or without leukocyte inclusion bodies or extra-hematological features, such as sensorineural deafness and renal impairment. MYH9RD can be misdiagnosed as an acquired form of thrombocytopenia including immune thrombocytopenic purpura (ITP). This leads to delayed diagnosis or administration of ineffective treatment. In the present study, we investigated the clinical and molecular characteristics of five unrelated Korean patients with MYH9RD and their family members, from four institutions. We reviewed clinical and laboratory data including extra-hematological manifestations. MYH9 pathogenic variants were detected by direct sequencing in all probands and the affected family members (N=10): two probands with c.5521G>A (p.Glu1841Lys) and one proband each with c.99G>T (p.Trp33Cys), c.287C>T (p.Ser96Leu), and c.3493C>T (p.Arg1165Cys). All patients had macrothrombocytopenia. Only the proband with Ser96Leu had extra-hematological manifestations. Past history revealed that two patients had been misdiagnosed with ITP and one of them had received a splenectomy. We validated the frequency of misdiagnosis (~20%) and genotype-phenotype correlations through a comprehensive review of previously reported cases of MYH9RD in Korea. It is important to suspect MYH9RD in patients with thrombocytopenia, and timely identification of macrothrombocytopenia and MYH9 pathogenic variants is required for early and accurate diagnosis of MYH9RD.
Deafness ; Delayed Diagnosis ; Diagnosis ; Diagnostic Errors ; Genetic Association Studies ; Humans ; Inclusion Bodies ; Korea ; Leukocytes ; Purpura, Thrombocytopenic, Idiopathic ; Splenectomy ; Thrombocytopenia

Primary age-related tauopathy (PART) is characterized by tau neurofibrillary tangles (NFTs) in the absence of amyloid plaque pathology. In the present study, we analyzed the distribution patterns of phosphorylated 43-kDa TAR DNA-binding protein (pTDP-43) in the brains of patients with PART. Immunohistochemistry and immunofluorescence double-labeling in multiple brain regions was performed on brain tissues from PART, Alzheimer's disease (AD), and aging control cases. We examined the regional distribution patterns of pTDP-43 intraneuronal inclusions in PART with Braak NFT stages > 0 and ≤ IV, and a Thal phase of 0 (no beta-amyloid present). We found four stages which indicated potentially sequential dissemination of pTDP-43 in PART. Stage I was characterized by the presence of pTDP-43 lesions in the amygdala, stage II by such lesions in the hippocampus, stage III by spread of pTDP-43 to the neocortex, and stage IV by pTDP-43 lesions in the putamen, pallidum, and insular cortex. In general, the distribution pattern of pTDP-43 pathology in PART cases was similar to the early TDP-43 stages reported in AD, but tended to be more restricted to the limbic system. However, there were some differences in the distribution patterns of pTDP-43 between PART and AD, especially in the dentate gyrus of the hippocampus. Positive correlations were found in PART between the Braak NFT stage and the pTDP-43 stage and density.
Aged ; Aged, 80 and over ; Aging ; metabolism ; pathology ; Brain ; metabolism ; pathology ; DNA-Binding Proteins ; metabolism ; Disease Progression ; Female ; Humans ; Immunohistochemistry ; Inclusion Bodies ; pathology ; Male ; Middle Aged ; Neurofibrillary Tangles ; metabolism ; pathology ; Neurons ; metabolism ; pathology ; Severity of Illness Index ; Tauopathies ; metabolism ; pathology

Abstract　　The promyelocytic leukemia (PML) gene encoded PML protein as a tumor suppressor protein, plays important roles in the occurrence and development of various cancers including acute promyelocytic leukemia. Recent studies have indicated that there are a variety of post-translational modifications of the PML protein, such as SUMOylation, ubiquitination, phosphorylation, and acetylation in cells. These modifications of the PML protein can directly affect the formation of PML nuclear bodies (PML-NBs), repair DNA damage, and modulate cell apoptosis. Furthermore, the abnormal modifications of PML not only result in the occurrence of hematopoietic tumors, but also are closely related to the drug-resistance of cancer. Therefore, investigating the post-translational modifications of PML is significant to uncover the mechanism of formation and functions of PML-NBs, thus contributing to the prevention and treatment of related hematopoietic tumors. In this review, the characteristics of the post-translational modifications of PML protein and the relationship between these modifications and functions of PML-NBs are summarized so as to provide the potential targets for the treatment of related cancers.
Humans ; Intranuclear Inclusion Bodies ; Leukemia, Promyelocytic, Acute ; Nuclear Proteins ; Promyelocytic Leukemia Protein ; Protein Processing, Post-Translational

No abstract available.
Cytoplasm* ; Inclusion Bodies*

Huntington disease (HD) is an inherited neurodegenerative disorder characterized by motor and cognitive dysfunction caused by expansion of polyglutamine (polyQ) repeat in exon 1 of huntingtin (HTT). In patients, the number of glutamine residues in polyQ tracts are over 35, and it is correlated with age of onset, severity, and disease progression. Expansion of polyQ increases the propensity for HTT protein aggregation, process known to be implicated in neurodegeneration. These pathological aggregates can be transmitted from neuron to another neuron, and this process may explain the pathological spreading of polyQ aggregates. Here, we developed an in vivo model for studying transmission of polyQ aggregates in a highly quantitative manner in real time. HTT exon 1 with expanded polyQ was fused with either N-terminal or C-terminal fragments of Venus fluorescence protein and expressed in pharyngeal muscles and associated neurons, respectively, of C. elegans. Transmission of polyQ proteins was detected using bimolecular fluorescence complementation (BiFC). Mutant polyQ (Q97) was transmitted much more efficiently than wild type polyQ (Q25) and forms numerous inclusion bodies as well. The transmission of Q97 was gradually increased with aging of animal. The animals with polyQ transmission exhibited degenerative phenotypes, such as nerve degeneration, impaired pharyngeal pumping behavior, and reduced life span. The C. elegans model presented here would be a useful in vivo model system for the study of polyQ aggregate propagation and might be applied to the screening of genetic and chemical modifiers of the propagation.
Age of Onset ; Aging ; Animals ; Complement System Proteins ; Disease Progression ; Exons ; Fluorescence ; Glutamine ; Humans ; Huntington Disease ; Inclusion Bodies ; Mass Screening ; Nerve Degeneration ; Neurodegenerative Diseases ; Neurons ; Pharyngeal Muscles ; Phenotype ; Venus

BMP-2 is a well-known TGF-beta related growth factor, having a significant role in bone and cartilage formation. It has been employed to promote bone formation in some clinical trials, and to differentiate mesenchymal stem cells into osteoblasts. However, it is difficult to obtain this protein in its soluble and active form. hBMP-2 is expressed as an inclusion body in the bacterial system. To continuously supply hBMP-2 for research, we optimized the refolding of recombinant hBMP-2 expressed in E. coli, and established an efficient method by using detergent and alkali. Using a heparin column, the recombinant hBMP-2 was purified with the correct refolding. Although combinatorial refolding remarkably enhanced the solubility of the inclusion body, a higher yield of active dimer form of hBMP-2 was obtained from one-step refolding with detergent. The refolded recombinant hBMP-2 induced alkaline phosphatase activity in mouse myoblasts, at ED₅₀ of 300-480ng/ml. Furthermore, the expressions of osteogenic markers were upregulated in hPDLSCs and hDPSCs. Therefore, using the process described in this study, the refolded hBMP-2 might be cost-effectively useful for various differentiation experiments in a laboratory.
Alkalies ; Alkaline Phosphatase ; Animals ; Cartilage ; Detergents ; Heparin ; Humans* ; Inclusion Bodies ; Mesenchymal Stromal Cells ; Methods ; Mice ; Myoblasts ; Osteoblasts ; Osteogenesis ; Solubility ; Stem Cells* ; Transforming Growth Factor beta

A dead dove was found on the road and submitted for diagnosis. The bird was severely emaciated, with deformation in its facial area. Grossly, white coalescing nodules were seen on the cut surface of the nasal cavity. Histopathologically, epithelial cells of the upper respiratory tract were markedly proliferated, with ballooning degeneration, down growth of the rete ridge, and large eosinophilic intracytoplasmic inclusion bodies. Parakeratotic hyperkeratosis and focal necrotic focus was present in the proliferative area. The facial bones showed partial bone resorption. Transmission electron microscopy revealed numerous viral particles in epithelial cells with dumbbell-shaped bodies, consistent with poxvirus.
Birds ; Bone Resorption ; Columbidae* ; Diagnosis ; Eosinophils ; Epithelial Cells ; Facial Bones ; Inclusion Bodies ; Microscopy, Electron ; Microscopy, Electron, Transmission ; Nasal Cavity ; Respiratory System ; Turtles* ; Virion

BACKGROUND: The cytopathic effects of cytomegalovirus (CMV) infection have been well described since the virus was first reported; however, the morphology of CMV infection has not been clearly studied. We examined the difference in detailed cytologic findings in bronchial washing cytology between liquid-based and conventionally prepared smears. METHODS: Bronchial washing cytology was processed using either the conventional preparation (CP) or liquid-based preparation (LBP). Sixty-nine cells with typical cytopathic effects of CMV infection were detected on CP slides and 18 cells on LBP slides. Using the image analyzer, area, circumference, major axis, and minor axis of the cytoplasm, nucleus, and intranuclear inclusion were measured in singly scattered CMV-infected cells, and histiocytes were used as a control. RESULTS: The mean cytoplasmic area of CMV-infected cells was 1.47 times larger than that of histiocytes in CP and 2.92 times larger in LBP (p<.05). The mean nuclear area of CMV-infected cells was 2.61 times larger than that of histiocytes in CP and 4.25 times larger in LBP (p<.05). The nucleus to cytoplasm ratio and intranuclear inclusion to cytoplasm ratio of the mean area, circumference, major axis, and minor axis in CP were larger than those in LBP (p<.05). CONCLUSIONS: The sizes of cytoplasm, nucleus, and intranuclear inclusion were larger in LBP than in CP, indicating that CMV-infected cells are easily detectable in LBP. However, the nucleus-to-cytoplasm ratio was larger in CP, suggesting that differentiation from malignancy or regenerative atypia requires caution in CP.
Axis, Cervical Vertebra ; Cytomegalovirus* ; Cytoplasm ; Histiocytes ; Intranuclear Inclusion Bodies ; Lung

The severe fever with thrombocytopenia syndrome virus (SFTSV) is a new member in the genus Phlebovirus of the family Bunyaviridae identified in China. The SFTSV is also the causative pathogen of an emerging infectious disease: severe fever with thrombocytopenia syndrome. Using immunofluorescent staining and confocal microscopy, the intracellular distribution of nucleocapsid protein (NP) in SFTSV-infected THP-1 cells was investigated with serial doses of SFTSV at different times after infection. Transmission electron microscopy was used to observe the ultrafine intracellular structure of SFTSV-infected THP-1 cells at different times after infection. SFTSV NP could form intracellular inclusion bodies in infected THP-1 cells. The association between NP-formed inclusion bodies and virus production was analyzed: the size of the inclusion body formed 3 days after infection was correlated with the viral load in supernatants collected 7 days after infection. These findings suggest that the inclusion bodies formed in SFTSV-infected THP-1 cells could be where the SFTSV uses host-cell proteins and intracellular organelles to produce new viral particles.
Cell Line ; China ; Humans ; Inclusion Bodies, Viral ; ultrastructure ; virology ; Macrophages ; ultrastructure ; virology ; Phlebotomus Fever ; virology ; Phlebovirus ; genetics ; physiology ; ultrastructure ; Thrombocytopenia ; virology