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1.
Cell ; 185(8): 1373-1388.e20, 2022 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-35381199

RESUMO

Systemic sclerosis (scleroderma, SSc) is an incurable autoimmune disease with high morbidity and mortality rates. Here, we conducted a population-scale single-cell genomic analysis of skin and blood samples of 56 healthy controls and 97 SSc patients at different stages of the disease. We found immune compartment dysfunction only in a specific subtype of diffuse SSc patients but global dysregulation of the stromal compartment, particularly in a previously undefined subset of LGR5+-scleroderma-associated fibroblasts (ScAFs). ScAFs are perturbed morphologically and molecularly in SSc patients. Single-cell multiome profiling of stromal cells revealed ScAF-specific markers, pathways, regulatory elements, and transcription factors underlining disease development. Systematic analysis of these molecular features with clinical metadata associates specific ScAF targets with disease pathogenesis and SSc clinical traits. Our high-resolution atlas of the sclerodermatous skin spectrum will enable a paradigm shift in the understanding of SSc disease and facilitate the development of biomarkers and therapeutic strategies.


Assuntos
Escleroderma Sistêmico , Células Cultivadas , Fibroblastos/metabolismo , Fibrose , Humanos , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Escleroderma Sistêmico/tratamento farmacológico , Escleroderma Sistêmico/genética , Pele/metabolismo
2.
Cell ; 182(4): 872-885.e19, 2020 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-32783915

RESUMO

Cell function and activity are regulated through integration of signaling, epigenetic, transcriptional, and metabolic pathways. Here, we introduce INs-seq, an integrated technology for massively parallel recording of single-cell RNA sequencing (scRNA-seq) and intracellular protein activity. We demonstrate the broad utility of INs-seq for discovering new immune subsets by profiling different intracellular signatures of immune signaling, transcription factor combinations, and metabolic activity. Comprehensive mapping of Arginase 1-expressing cells within tumor models, a metabolic immune signature of suppressive activity, discovers novel Arg1+ Trem2+ regulatory myeloid (Mreg) cells and identifies markers, metabolic activity, and pathways associated with these cells. Genetic ablation of Trem2 in mice inhibits accumulation of intra-tumoral Mreg cells, leading to a marked decrease in dysfunctional CD8+ T cells and reduced tumor growth. This study establishes INs-seq as a broadly applicable technology for elucidating integrated transcriptional and intra-cellular maps and identifies the molecular signature of myeloid suppressive cells in tumors.


Assuntos
Glicoproteínas de Membrana/metabolismo , Neoplasias/patologia , RNA Citoplasmático Pequeno/química , Receptores Imunológicos/metabolismo , Animais , Arginase/genética , Arginase/metabolismo , Linfócitos T CD8-Positivos/citologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Células Dendríticas/citologia , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/metabolismo , Feminino , Regulação da Expressão Gênica , Humanos , Leucócitos Mononucleares/citologia , Leucócitos Mononucleares/metabolismo , Lipopolissacarídeos/farmacologia , Glicoproteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos C57BL , Neoplasias/imunologia , Neoplasias/metabolismo , RNA Citoplasmático Pequeno/metabolismo , Receptores Imunológicos/genética , Análise de Sequência de RNA , Análise de Célula Única , Fatores de Transcrição/metabolismo , Microambiente Tumoral , Fator de Necrose Tumoral alfa/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno
3.
Nat Med ; 27(3): 491-503, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33619369

RESUMO

Multiple myeloma (MM) is a neoplastic plasma-cell disorder characterized by clonal proliferation of malignant plasma cells. Despite extensive research, disease heterogeneity within and between treatment-resistant patients is poorly characterized. In the present study, we conduct a prospective, multicenter, single-arm clinical trial (NCT04065789), combined with longitudinal single-cell RNA-sequencing (scRNA-seq) to study the molecular dynamics of MM resistance mechanisms. Newly diagnosed MM patients (41), who either failed to respond or experienced early relapse after a bortezomib-containing induction regimen, were enrolled to evaluate the safety and efficacy of a daratumumab, carfilzomib, lenalidomide and dexamethasone combination. The primary clinical endpoint was safety and tolerability. Secondary endpoints included overall response rate, progression-free survival and overall survival. Treatment was safe and well tolerated; deep and durable responses were achieved. In prespecified exploratory analyses, comparison of 41 primary refractory and early relapsed patients, with 11 healthy subjects and 15 newly diagnosed MM patients, revealed new MM molecular pathways of resistance, including hypoxia tolerance, protein folding and mitochondria respiration, which generalized to larger clinical cohorts (CoMMpass). We found peptidylprolyl isomerase A (PPIA), a central enzyme in the protein-folding response pathway, as a potential new target for resistant MM. CRISPR-Cas9 deletion of PPIA or inhibition of PPIA with a small molecule inhibitor (ciclosporin) significantly sensitizes MM tumor cells to proteasome inhibitors. Together, our study defines a roadmap for integrating scRNA-seq in clinical trials, identifies a signature of highly resistant MM patients and discovers PPIA as a potent therapeutic target for these tumors.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/patologia , Análise de Célula Única/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/administração & dosagem , Estudos de Casos e Controles , Dexametasona/administração & dosagem , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Lenalidomida/administração & dosagem , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Oligopeptídeos/administração & dosagem , Resultado do Tratamento
4.
Cells ; 9(7)2020 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-32668704

RESUMO

Granulocyte-monocyte colony stimulating factor (GM-CSF) is used as an adjuvant in various clinical and preclinical studies with contradictory results. These were attributed to opposing effects of GM-CSF on the immune or myeloid systems of the treated patients or to lack of optimal dosing regimens. The results of the present study point to inter-tumor heterogeneity as a possible mechanism accounting for the contrasting responses to GM-CSF incorporating therapies. Employing xenograft models of human melanomas in nude mice developed in our lab, we detected differential functional responses of melanomas from different patients to GM-CSF both in vitro as well as in vivo. Whereas cells of one melanoma acquired pro metastatic features following exposure to GM-CSF, cells from another melanoma either did not respond or became less malignant. We propose that inter-melanoma heterogeneity as manifested by differential responses of melanoma cells (and perhaps also of other tumor) to GM-CSF may be developed into a predictive marker providing a tool to segregate melanoma patients who will benefit from GM-CSF therapy from those who will not.


Assuntos
Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacologia , Melanoma/patologia , Neoplasias Cutâneas/patologia , Animais , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Encéfalo/patologia , Linhagem Celular Tumoral , Microambiente Celular/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Humanos , Interleucina-1alfa/metabolismo , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Solubilidade , Migração Transendotelial e Transepitelial/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo
5.
Clin Exp Metastasis ; 35(5-6): 369-378, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29722001

RESUMO

The development of melanoma brain metastasis is largely dependent on mutual interactions between the melanoma cells and cells in the brain microenvironment. Here, we report that the extracellular cysteine protease inhibitor cystatin C (CysC) is involved in these interactions. Microglia-derived factors upregulated CysC secretion by melanoma. Similarly, melanoma-derived factors upregulated CysC secretion by microglia. Whereas CysC enhanced melanoma cell migration through a layer of brain endothelial cells, it inhibited the migration of microglia cells toward melanoma cells. CysC was also found to promote the formation of melanoma three-dimensional structures in matrigel. IHC analysis revealed increased expression levels of CysC in the brain of immune-deficient mice bearing xenografted human melanoma brain metastasis compared to the brain of control mice. Based on these in vitro and in vivo experiments we hypothesize that CysC promotes melanoma brain metastasis. Increased expression levels of CysC were detected in the regenerating brain of mice after stroke. Post-stroke brain with melanoma brain metastasis showed an even stronger expression of CysC. The in vitro induction of stroke-like conditions in brain microenvironmental cells increased the levels of CysC in the secretome of microglia cells, but not in the secretome of brain endothelial cells. The similarities between melanoma brain metastasis and stroke with respect to CysC expression by and secretion from microglia cells suggest that CysC may be involved in shared pathways between brain metastasis and post-stroke regeneration. This manifests the tendency of tumor cells to highjack physiological molecular pathways in their progression.


Assuntos
Neoplasias Encefálicas/genética , Cistatina C/genética , Melanoma/genética , Microglia/metabolismo , Animais , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/secundário , Linhagem Celular Tumoral , Movimento Celular/genética , Colágeno/farmacologia , Inibidores de Cisteína Proteinase/metabolismo , Combinação de Medicamentos , Regulação Neoplásica da Expressão Gênica , Humanos , Laminina/farmacologia , Melanoma/patologia , Camundongos , Microglia/patologia , Metástase Neoplásica , Proteoglicanas/farmacologia , Transdução de Sinais , Microambiente Tumoral/genética , Ensaios Antitumorais Modelo de Xenoenxerto
6.
Cell Stress Chaperones ; 22(3): 345-355, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28324352

RESUMO

Tomato yellow leaf curl virus (TYLCV) is a begomovirus infecting tomato plants worldwide. TYLCV needs a healthy host environment to ensure a successful infection cycle for long periods. Hence, TYLCV restrains its destructive effect and induces neither a hypersensitive response nor cell death in infected tomatoes. On the contrary, TYLCV counteracts cell death induced by other factors, such as inactivation of HSP90 functionality. Suppression of plant death is associated with the inhibition of the ubiquitin 26S proteasome degradation and with a deactivation of the heat shock transcription factor HSFA2 pathways (including decreased HSP17 levels). The goal of the current study was to find if the individual TYLCV genes were capable of suppressing HSP90-dependent death and HSFA2 deactivation. The expression of C2 (C3 and CP to a lesser extent) caused a decrease in the severity of death phenotypes, while the expression of V2 (C1 and C4 to a lesser extent) strengthened cell death. However, C2 or V2 markedly affected stress response under conditions of viral infection. The downregulation of HSFA2 signaling, initiated by the expression of C1 and V2, was detected in the absence of virus infection, but was enhanced in infected plants, while CP and C4 mitigated HSFA2 levels only in the infected tomatoes. The dependence of analyzed plant stress response suppression on the interaction of the expressed genes with the environment created by the whole virus infection was more pronounced than on the expression of individual TYLCV genes.


Assuntos
Begomovirus/genética , Proteínas de Plantas/metabolismo , Solanum lycopersicum/metabolismo , Proteínas Virais/metabolismo , 3,3'-Diaminobenzidina/química , Begomovirus/metabolismo , Inativação Gênica , Proteínas de Choque Térmico HSP90/genética , Proteínas de Choque Térmico HSP90/metabolismo , Fatores de Transcrição de Choque Térmico/genética , Fatores de Transcrição de Choque Térmico/metabolismo , Peróxido de Hidrogênio/análise , Peróxido de Hidrogênio/química , Solanum lycopersicum/virologia , Fotografação , Doenças das Plantas/virologia , Folhas de Planta/metabolismo , Folhas de Planta/virologia , Proteínas de Plantas/genética , Plasmídeos/genética , Plasmídeos/metabolismo , Estresse Fisiológico , Temperatura , Proteínas Virais/genética
7.
Mol Plant Pathol ; 17(2): 247-60, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25962748

RESUMO

To ensure a successful long-term infection cycle, begomoviruses must restrain their destructive effect on host cells and prevent drastic plant responses, at least in the early stages of infection. The monopartite begomovirus Tomato yellow leaf curl virus (TYLCV) does not induce a hypersensitive response and cell death on whitefly-mediated infection of virus-susceptible tomato plants until diseased tomatoes become senescent. The way in which begomoviruses evade plant defences and interfere with cell death pathways is still poorly understood. We show that the chaperone HSP90 (heat shock protein 90) and its co-chaperone SGT1 (suppressor of the G2 allele of Skp1) are involved in the establishment of TYLCV infection. Inactivation of HSP90, as well as silencing of the Hsp90 and Sgt1 genes, leads to the accumulation of damaged ubiquitinated proteins and to a cell death phenotype. These effects are relieved under TYLCV infection. HSP90-dependent inactivation of 26S proteasome degradation and the transcriptional activation of the heat shock transcription factors HsfA2 and HsfB1 and of the downstream genes Hsp17 and Apx1/2 are suppressed in TYLCV-infected tomatoes. Following suppression of the plant stress response, TYLCV can replicate and accumulate in a permissive environment.


Assuntos
Begomovirus/patogenicidade , Proteínas de Choque Térmico HSP90/antagonistas & inibidores , Células Vegetais/virologia , Doenças das Plantas/virologia , Proteínas de Plantas/metabolismo , Solanum lycopersicum/citologia , Solanum lycopersicum/virologia , Proteínas do Capsídeo/metabolismo , Morte Celular , Inativação Gênica , Genes de Plantas , Proteínas de Fluorescência Verde/metabolismo , Proteínas de Choque Térmico HSP90/metabolismo , Temperatura Alta , Modelos Biológicos , Folhas de Planta/citologia , Folhas de Planta/virologia , Agregados Proteicos , Ubiquitinação
8.
Sci Rep ; 6: 19715, 2016 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-26792235

RESUMO

Cultured tomatoes are often exposed to a combination of extreme heat and infection with Tomato yellow leaf curl virus (TYLCV). This stress combination leads to intense disease symptoms and yield losses. The response of TYLCV-susceptible and resistant tomatoes to heat stress together with viral infection was compared. The plant heat-stress response was undermined in TYLCV infected plants. The decline correlated with the down-regulation of heat shock transcription factors (HSFs) HSFA2 and HSFB1, and consequently, of HSF-regulated genes Hsp17, Apx1, Apx2 and Hsp90. We proposed that the weakened heat stress response was due to the decreased capacity of HSFA2 to translocate into the nuclei of infected cells. All the six TYLCV proteins were able to interact with tomato HSFA2 in vitro, moreover, coat protein developed complexes with HSFA2 in nuclei. Capturing of HSFA2 by viral proteins could suppress the transcriptional activation of heat stress response genes. Application of both heat and TYLCV stresses was accompanied by the development of intracellular large protein aggregates containing TYLCV proteins and DNA. The maintenance of cellular chaperones in the aggregated state, even after recovery from heat stress, prevents the circulation of free soluble chaperones, causing an additional decrease in stress response efficiency.


Assuntos
Begomovirus/fisiologia , Resposta ao Choque Térmico , Interações Hospedeiro-Patógeno , Temperatura Alta , Doenças das Plantas/virologia , Solanum lycopersicum/crescimento & desenvolvimento , Solanum lycopersicum/virologia , Resistência à Doença , Suscetibilidade a Doenças , Perfilação da Expressão Gênica , Folhas de Planta/metabolismo , Folhas de Planta/virologia , Proteínas de Plantas/metabolismo , Agregados Proteicos , Ligação Proteica , Transporte Proteico , Proteoma , Proteínas Virais/genética , Proteínas Virais/metabolismo
9.
Sci Rep ; 5: 9967, 2015 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-25940862

RESUMO

The spread of Tomato yellow leaf curl virus (TYLCV) was accompanied by the formation of coat protein (CP) aggregates of increasing size in the cytoplasm and nucleus of infected tomato (Solanum lycopersicum) cells. In order to better understand the TYLCV-host interaction, we investigated the properties and the subcellular accumulation pattern of the non-structural viral protein V2. CP and V2 are the only sense-oriented genes on the virus circular single-stranded DNA genome. Similar to CP, V2 localized to cytoplasmic aggregates of increasing size and as infection progressed was also found in nuclei, where it co-localized with CP. V2 was associated with viral genomic DNA molecules, suggesting that V2 functions as a DNA shuttling protein. The formation and the 26S proteasome-mediated degradation of V2 aggregates were dependent on the integrity of the actin and microtubule cytoskeleton. We propose that the cytoskeleton-dependent formation and growth of V2 aggregates play an important role during TYLCV infection, and that microtubules and actin filaments are important for the delivery of V2 to the 26S proteasome.


Assuntos
Begomovirus/fisiologia , Proteínas do Capsídeo/metabolismo , Citoesqueleto/virologia , DNA Viral/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Solanum lycopersicum/virologia , Begomovirus/patogenicidade , Proteínas do Capsídeo/genética , Citoesqueleto/metabolismo , DNA Viral/genética , Dimerização , Genes Virais/genética , Genoma Viral/genética , Solanum lycopersicum/metabolismo , Complexos Multiproteicos , Ligação Proteica
10.
Pest Manag Sci ; 70(10): 1632-9, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24464776

RESUMO

BACKGROUND: Tomato yellow leaf curl virus (TYLCV) is a begomovirus infecting tomato cultures worldwide. TYLCV is transmitted to plants by the whitefly Bemisia tabaci. Once in the plant, the virus is subjected to attack by the host-plant defences, which may include sequestration in aggregates, proteolysis, ubiquitination, 26S proteasome degradation and autophagy. Elucidating how the virus avoids destruction will make it possible to understand infection and possibly devise countermeasures. RESULTS: The accumulation of viral coat protein (CP) and of viral DNA in plants is a marker of a successful virus transmission by B. tabaci. In response to infection, tomato tissues display multiple ways of degrading TYLCV proteins and DNA. In this study it is shown that CP (in soluble and insoluble states) is the target of protease digestion, 26S proteasome degradation and autophagy. The highest degradation capacity was detected among soluble proteins and proteins in large aggregates/inclusion bodies; cytoplasmic extracts displayed higher activity than nuclear fractions. The very same fractions possessed the highest capacity to degrade viral genomic DNA. Separately, 26S proteasome degradation was associated with large aggregates (more pronounced in the nuclear than in the cytoplasmic fractions), which are indicators of a successful abduction of plants by viruses. Autophagy/lysosome/vacuole degradation was a characteristic of intermediate aggregates, sequestering the CP in the cytoplasm and retarding the development of large aggregates. Chloroplast proteases were active in soluble as well as in insoluble protein extracts. CONCLUSIONS: To the best of the authors' knowledge, this study is the first attempt to identify elements of the virus-targeted degradation machinery, which is a part of the plant response to virus invasion.


Assuntos
Begomovirus/imunologia , Begomovirus/metabolismo , DNA Viral/metabolismo , Doenças das Plantas/imunologia , Doenças das Plantas/virologia , Solanum lycopersicum/imunologia , Solanum lycopersicum/virologia , Animais , Autofagia , Proteínas do Capsídeo/metabolismo , Hemípteros/virologia , Insetos Vetores/virologia , Peptídeo Hidrolases/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo
11.
PLoS One ; 8(7): e70280, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23894631

RESUMO

A functional capsid protein (CP) is essential for host plant infection and insect transmission of Tomato yellow leaf curl virus (TYLCV) and other monopartite begomoviruses. We have previously shown that TYLCV CP specifically interacts with the heat shock protein 70 (HSP70) of the virus insect vector, Bemisia tabaci. Here we demonstrate that during the development of tomato plant infection with TYLCV, a significant amount of HSP70 shifts from a soluble form into insoluble aggregates. CP and HSP70 co-localize in these aggregates, first in the cytoplasm, then in the nucleus of cells associated with the vascular system. CP-HSP70 interaction was demonstrated by co-immunopreciptation in cytoplasmic - but not in nuclear extracts from leaf and stem. Inhibition of HSP70 expression by quercetin caused a decrease in the amount of nuclear CP aggregates and a re-localization of a GFP-CP fusion protein from the nucleus to the cytoplasm. HSP70 inactivation resulted in a decrease of TYLCV DNA levels, demonstrating the role of HSP70 in TYLCV multiplication in planta. The current study reveals for the first time the involvement of plant HSP70 in TYLCV CP intracellular movement. As described earlier, nuclear aggregates contained TYLCV DNA-CP complexes and infectious virions. Showing that HSP70 localizes in these large nuclear aggregates infers that these structures operate as nuclear virus factories.


Assuntos
Begomovirus/fisiologia , Proteínas do Capsídeo/metabolismo , Regulação da Expressão Gênica de Plantas , Proteínas de Choque Térmico HSP70/genética , Proteínas de Choque Térmico HSP70/metabolismo , Solanum lycopersicum/virologia , Antioxidantes/farmacologia , Begomovirus/metabolismo , Núcleo Celular/metabolismo , Citoplasma/metabolismo , Citoplasma/virologia , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Solanum lycopersicum/genética , Solanum lycopersicum/metabolismo , Folhas de Planta/metabolismo , Folhas de Planta/virologia , Caules de Planta/metabolismo , Caules de Planta/virologia , Ligação Proteica , Transporte Proteico/efeitos dos fármacos , Quercetina/farmacologia , Proteínas Virais de Fusão/genética , Proteínas Virais de Fusão/metabolismo
12.
Virus Res ; 171(1): 33-43, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23099086

RESUMO

Tomato yellow leaf curl virus (TYLCV) coat protein (CP) accumulated in tomato leaves during infection. The CP was immuno-detected in the phloem associated cells. At the early stages of infection, punctate signals were detected in the cytoplasm, while in the later stages aggregates of increasing size were localized in cytoplasm and nuclei. Sedimentation of protein extracts through sucrose gradients confirmed that progress of infection was accompanied by the formation of CP aggregates of increasing size. Genomic ssDNA was found in the cytoplasm and in the nucleus, while the dsDNA replicative form was exclusively associated with the nucleus. CP-DNA complexes were detected by immuno-capture PCR in nuclear and cytoplasmic large aggregates. Nuclear aggregates contained infectious particles transmissible to test plants by whiteflies. In contrast to susceptible tomatoes, the formation of large CP aggregates in resistant plants was delayed. By experimentally changing the level of resistance/susceptibility of plants, we showed that maintenance of midsized CP aggregates was associated with resistance, while large aggregates where characteristic of susceptibility. We propose that sequestering of virus CP into midsized aggregates and retarding the formation of large insoluble aggregates containing infectious particles is part of the response of resistant plants to TYLCV.


Assuntos
Begomovirus/imunologia , Begomovirus/metabolismo , Proteínas do Capsídeo/metabolismo , Doenças das Plantas/imunologia , Doenças das Plantas/virologia , Solanum lycopersicum/imunologia , Solanum lycopersicum/virologia , Proteínas do Capsídeo/genética , Folhas de Planta/metabolismo , Folhas de Planta/virologia , Plantas Geneticamente Modificadas , Frações Subcelulares
13.
Viruses ; 4(10): 2218-32, 2012 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-23202461

RESUMO

During infection, many viruses induce cellular remodeling, resulting in the formation of insoluble aggregates/inclusions, usually containing viral structural proteins. Identification of aggregates has become a useful diagnostic tool for certain viral infections. There is wide variety of viral aggregates, which differ by their location, size, content and putative function. The role of aggregation in the context of a specific virus is often poorly understood, especially in the case of plant viruses. The aggregates are utilized by viruses to house a large complex of proteins of both viral and host origin to promote virus replication, translation, intra- and intercellular transportation. Aggregated structures may protect viral functional complexes from the cellular degradation machinery. Alternatively, the activation of host defense mechanisms may involve sequestration of virus components in aggregates, followed by their neutralization as toxic for the host cell. The diversity of virus-induced aggregates in mammalian and plant cells is the subject of this review.


Assuntos
Corpos de Inclusão Viral/fisiologia , Células Vegetais/virologia , Vírus de Plantas/patogenicidade , Plantas/virologia , Animais , Transporte Biológico , Núcleo Celular/virologia , Citoplasma/virologia , Vírus de DNA/genética , Vírus de DNA/patogenicidade , Vírus de DNA/fisiologia , Interações Hospedeiro-Patógeno , Mamíferos/virologia , Vírus de Plantas/genética , Vírus de Plantas/fisiologia , Vírus de RNA/genética , Vírus de RNA/patogenicidade , Vírus de RNA/fisiologia , Montagem de Vírus , Viroses/virologia , Replicação Viral
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