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1.
Artigo em Inglês | MEDLINE | ID: mdl-32730915

RESUMO

In December 2019, the first case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) infection was reported. In only few weeks it has caused a global pandemic, with mortality reaching 3.4%, mostly due to a severe pneumonia. However, the impact of SARS-CoV-2 virus on the central nervous system (CNS) and mental health outcomes remains unclear. Previous studies have demonstrated the presence of other types of coronaviruses in the brain, especially in the brainstem. There is evidence that the novel coronavirus can penetrate CNS through the olfactory or circulatory route as well as it can have an indirect impact on the brain by causing cytokine storm. There are also first reports of neurological signs in patients infected by the SARS-Cov-2. They show that COVID-19 patients have neurologic manifestations like acute cerebrovascular disease, conscious disturbance, taste and olfactory disturbances. In addition, there are studies showing that certain psychopathological symptoms might appear in infected patients, including those related to mood and psychotic disorders as well as post-traumatic stress disorder. Accumulating evidence also indicates that the pandemic might have a great impact on mental health from the global perspective, with medical workers being particularly vulnerable. In this article, we provide a review of studies investigating the impact of the SARS-CoV-2 on the CNS and mental health outcomes. We describe neurobiology of the virus, highlighting the relevance to mental disorders. Furthermore, this article summarizes the impact of the SARS-CoV-2 from the public health perspective. Finally, we present a critical appraisal of evidence and indicate future directions for studies in this field.


Assuntos
Infecções por Coronavirus/psicologia , Transtornos Mentais/psicologia , Saúde Mental , Pneumonia Viral/psicologia , Betacoronavirus , Encéfalo/virologia , Infecções por Coronavirus/complicações , Humanos , Transtornos Mentais/complicações , Transtornos Mentais/etiologia , Doenças do Sistema Nervoso/etiologia , Pandemias , Pneumonia Viral/complicações , Resultado do Tratamento
2.
Nat Commun ; 11(1): 4894, 2020 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-32994400

RESUMO

Identification of the complete set of translated genes of viruses is important to understand viral replication and pathogenesis as well as for therapeutic approaches to control viral infection. Here, we use chemical proteomics, integrating bio-orthogonal non-canonical amino acid tagging and high-resolution mass spectrometry, to characterize the newly synthesized herpes simplex virus 1 (HSV-1) proteome in infected cells. In these infected cells, host cellular protein synthesis is shut-off, increasing the chance to preferentially detect viral proteomes. We identify nine previously cryptic orphan protein coding sequences whose translated products are expressed in HSV-1-infected cells. Functional characterization of one identified protein, designated piUL49, shows that it is critical for HSV-1 neurovirulence in vivo by regulating the activity of virally encoded dUTPase, a key enzyme that maintains accurate DNA replication. Our results demonstrate that cryptic orphan protein coding genes of HSV-1, and probably other large DNA viruses, remain to be identified.


Assuntos
Encefalite por Herpes Simples/virologia , Herpesvirus Humano 1/patogenicidade , Pirofosfatases/metabolismo , Proteínas Virais/metabolismo , Fatores de Virulência/metabolismo , Animais , Encéfalo/patologia , Encéfalo/virologia , Chlorocebus aethiops , Replicação do DNA , Modelos Animais de Doenças , Encefalite por Herpes Simples/patologia , Feminino , Genes Virais/genética , Células HEK293 , Células HeLa , Herpesvirus Humano 1/genética , Humanos , Camundongos , Biossíntese de Proteínas , Proteômica/métodos , Células Vero , Proteínas Virais/genética , Fatores de Virulência/genética , Replicação Viral
4.
ACS Chem Neurosci ; 11(18): 2789-2792, 2020 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-32880441

RESUMO

The recent outbreak of Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) from Wuhan, China, was caused by a single-stranded RNA virus which has kept the entire world stranded. The outbreak was first diagnosed with respiratory illness, but recent findings of acute necrotizing hemorrhage of brain, brain encephalopathy, and the presence of the virus in the cerebrospinal fluid (CSF) have unveiled its neuroinvasivness. Various clinical features related to the central nervous system (CNS) and peripheral nervous system (PNS) due to COVID-19 infection are now identified. We demonstrate here an apparent similarity in neurological disorders of COVID-19 with CNS tuberculosis, which suggests that some anti-tubercular drugs may be used as therapeutic agents against COVID-19 infection.


Assuntos
Doenças do Sistema Nervoso Central/virologia , Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Tuberculose do Sistema Nervoso Central , Animais , Betacoronavirus , Encéfalo/virologia , Humanos , Pandemias , Tuberculose do Sistema Nervoso Central/imunologia , Tuberculose do Sistema Nervoso Central/patologia , Tuberculose do Sistema Nervoso Central/fisiopatologia
5.
J Neurovirol ; 26(5): 631-641, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32876900

RESUMO

A subset of patients with coronavirus 2 disease (COVID-19) experience neurological complications. These complications include loss of sense of taste and smell, stroke, delirium, and neuromuscular signs and symptoms. The etiological agent of COVID-19 is SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), an RNA virus with a glycoprotein-studded viral envelope that uses ACE2 (angiotensin-converting enzyme 2) as a functional receptor for infecting the host cells. Thus, the interaction of the envelope spike proteins with ACE2 on host cells determines the tropism and virulence of SARS-CoV-2. Loss of sense of taste and smell is an initial symptom of COVID-19 because the virus enters the nasal and oral cavities first and the epithelial cells are the receptors for these senses. Stroke in COVID-19 patients is likely a consequence of coagulopathy and injury to cerebral vascular endothelial cells that cause thrombo-embolism and stroke. Delirium and encephalopathy in acute and post COVID-19 patients are likely multifactorial and secondary to hypoxia, metabolic abnormalities, and immunological abnormalities. Thus far, there is no clear evidence that coronaviruses cause inflammatory neuromuscular diseases via direct invasion of peripheral nerves or muscles or via molecular mimicry. It appears that most of neurologic complications in COVID-19 patients are indirect and as a result of a bystander injury to neurons.


Assuntos
Betacoronavirus/patogenicidade , Encefalopatias/complicações , Infecções por Coronavirus/complicações , Transtornos do Olfato/complicações , Pneumonia Viral/complicações , Embolia Pulmonar/complicações , Acidente Vascular Cerebral/complicações , Encéfalo/irrigação sanguínea , Encéfalo/patologia , Encéfalo/virologia , Encefalopatias/imunologia , Encefalopatias/patologia , Encefalopatias/virologia , Efeito Espectador , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Células Epiteliais/patologia , Células Epiteliais/virologia , Regulação da Expressão Gênica , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Humanos , Pulmão/irrigação sanguínea , Pulmão/patologia , Pulmão/virologia , Neurônios/patologia , Neurônios/virologia , Transtornos do Olfato/imunologia , Transtornos do Olfato/patologia , Transtornos do Olfato/virologia , Pandemias , Peptidil Dipeptidase A/genética , Peptidil Dipeptidase A/imunologia , Pneumonia Viral/imunologia , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Embolia Pulmonar/imunologia , Embolia Pulmonar/patologia , Embolia Pulmonar/virologia , Transdução de Sinais/genética , Transdução de Sinais/imunologia , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/imunologia , Acidente Vascular Cerebral/imunologia , Acidente Vascular Cerebral/patologia , Acidente Vascular Cerebral/virologia
6.
ACS Chem Neurosci ; 11(17): 2489-2491, 2020 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-32840109

RESUMO

Coronavirus Disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a severe public health problem with a high rate of morbidity and mortality. A mounting number of clinical investigations illustrate that COVID-19 patients suffer from neurologic conditions in addition to respiratory symptoms. In a recent article, Yuen and colleagues present the first experimental evidence of SARS-CoV-2 infection in the human central nervous system using induced pluripotent stem cells (iPSCs)-derived platform including human neural progenitor cells, neurospheres, and three-dimensional brain organoids (Yuen, K.Y., and Huang, J.D. et al. (2020) Cell Res. DOI: 10.1038/s41422-020-0390-x).


Assuntos
Betacoronavirus , Encéfalo/patologia , Infecções por Coronavirus/patologia , Infecções por Coronavirus/transmissão , Células-Tronco Pluripotentes Induzidas/patologia , Pneumonia Viral/patologia , Pneumonia Viral/transmissão , Encéfalo/virologia , Estudos de Viabilidade , Humanos , Células-Tronco Pluripotentes Induzidas/virologia , Organoides/patologia , Organoides/virologia , Pandemias
7.
Crit Care ; 24(1): 495, 2020 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-32787909

RESUMO

BACKGROUND: Post-mortem studies can provide important information for understanding new diseases and small autopsy case series have already reported different findings in COVID-19 patients. METHODS: We evaluated whether some specific post-mortem features are observed in these patients and if these changes are related to the presence of the virus in different organs. Complete macroscopic and microscopic autopsies were performed on different organs in 17 COVID-19 non-survivors. Presence of SARS-CoV-2 was evaluated with immunohistochemistry (IHC) in lung samples and with real-time reverse-transcription polymerase chain reaction (RT-PCR) test in the lung and other organs. RESULTS: Pulmonary findings revealed early-stage diffuse alveolar damage (DAD) in 15 out of 17 patients and microthrombi in small lung arteries in 11 patients. Late-stage DAD, atypical pneumocytes, and/or acute pneumonia were also observed. Four lung infarcts, two acute myocardial infarctions, and one ischemic enteritis were observed. There was no evidence of myocarditis, hepatitis, or encephalitis. Kidney evaluation revealed the presence of hemosiderin in tubules or pigmented casts in most patients. Spongiosis and vascular congestion were the most frequently encountered brain lesions. No specific SARS-CoV-2 lesions were observed in any organ. IHC revealed positive cells with a heterogeneous distribution in the lungs of 11 of the 17 (65%) patients; RT-PCR yielded a wide distribution of SARS-CoV-2 in different tissues, with 8 patients showing viral presence in all tested organs (i.e., lung, heart, spleen, liver, colon, kidney, and brain). CONCLUSIONS: In conclusion, autopsies revealed a great heterogeneity of COVID-19-associated organ injury and the remarkable absence of any specific viral lesions, even when RT-PCR identified the presence of the virus in many organs.


Assuntos
Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/virologia , Pneumonia Viral/virologia , Idoso , Autopsia , Encéfalo/virologia , Colo/virologia , Infecções por Coronavirus/terapia , Feminino , Coração/virologia , Humanos , Rim/virologia , Fígado/virologia , Pulmão/virologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/terapia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Baço/virologia
9.
J Neurovirol ; 26(5): 802-804, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32797352
10.
J Neurovirol ; 26(5): 619-630, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32839951

RESUMO

The recent pandemic outbreak of coronavirus is pathogenic and a highly transmittable viral infection caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2). In this time of ongoing pandemic, many emerging reports suggested that the SARS-CoV-2 has inimical effects on neurological functions, and even causes serious neurological damage. The neurological symptoms associated with COVID-19 include headache, dizziness, depression, anosmia, encephalitis, stroke, epileptic seizures, and Guillain-Barre syndrome along with many others. The involvement of the CNS may be related with poor prognosis and disease worsening. Here, we review the evidence of nervous system involvement and currently known neurological manifestations in COVID-19 infections caused by SARS-CoV-2. We prioritize the 332 human targets of SARS-CoV-2 according to their association with brain-related disease and identified 73 candidate genes. We prioritize these 73 genes according to their spatio-temporal expression in the different regions of brain and also through evolutionary intolerance analysis. The prioritized genes could be considered potential indicators of COVID-19-associated neurological symptoms and thus act as a possible therapeutic target for the prevention and treatment of CNS manifestations associated with COVID-19 patients.


Assuntos
Betacoronavirus/patogenicidade , Encéfalo/metabolismo , Infecções por Coronavirus/genética , Interações Hospedeiro-Patógeno/genética , Proteínas do Tecido Nervoso/genética , Pneumonia Viral/genética , Proteínas Virais/genética , Encéfalo/patologia , Encéfalo/virologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Depressão , Tontura/complicações , Tontura/genética , Tontura/patologia , Tontura/virologia , Encefalite/complicações , Encefalite/genética , Encefalite/patologia , Encefalite/virologia , Síndrome de Guillain-Barré/complicações , Síndrome de Guillain-Barré/genética , Síndrome de Guillain-Barré/patologia , Síndrome de Guillain-Barré/virologia , Cefaleia/complicações , Cefaleia/genética , Cefaleia/patologia , Cefaleia/virologia , Humanos , Proteínas do Tecido Nervoso/classificação , Proteínas do Tecido Nervoso/metabolismo , Transtornos do Olfato/complicações , Transtornos do Olfato/genética , Transtornos do Olfato/patologia , Transtornos do Olfato/virologia , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Mapeamento de Interação de Proteínas , Convulsões/complicações , Convulsões/genética , Convulsões/patologia , Convulsões/virologia , Índice de Gravidade de Doença , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/genética , Acidente Vascular Cerebral/patologia , Acidente Vascular Cerebral/virologia , Proteínas Virais/metabolismo
11.
Neurobiol Dis ; 143: 105007, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32622086

RESUMO

In the first two decades of the 21st century, there have been three outbreaks of severe respiratory infections caused by highly pathogenic coronaviruses (CoVs) around the world: the severe acute respiratory syndrome (SARS) by the SARS-CoV in 2002-2003, the Middle East respiratory syndrome (MERS) by the MERS-CoV in June 2012, and Coronavirus Disease 2019 (COVID-19) by the SARS-CoV-2 presently affecting most countries In all of these, fatalities are a consequence of a multiorgan dysregulation caused by pulmonary, renal, cardiac, and circulatory damage; however, COVID patients may show significant neurological signs and symptoms such as headache, nausea, vomiting, and sensory disturbances, the most prominent being anosmia and ageusia. The neuroinvasive potential of CoVs might be responsible for at least part of these symptoms and may contribute to the respiratory failure observed in affected patients. Therefore, in the present manuscript, we have reviewed the available preclinical evidence on the mechanisms and consequences of CoVs-induced CNS damage, and highlighted the potential role of CoVs in determining or aggravating acute and long-term neurological diseases in infected individuals. We consider that a widespread awareness of the significant neurotropism of CoVs might contribute to an earlier recognition of the signs and symptoms of viral-induced CNS damage. Moreover, a better understanding of the cellular and molecular mechanisms by which CoVs affect CNS function and cause CNS damage could help in planning new strategies for prognostic evaluation and targeted therapeutic intervention.


Assuntos
Betacoronavirus , Encéfalo/virologia , Infecções por Coronavirus/epidemiologia , Doenças do Sistema Nervoso/epidemiologia , Pneumonia Viral/epidemiologia , Animais , Encéfalo/fisiopatologia , Infecções por Coronavirus/fisiopatologia , Humanos , Doenças do Sistema Nervoso/fisiopatologia , Pandemias , Pneumonia Viral/fisiopatologia , Síndrome Respiratória Aguda Grave/epidemiologia , Síndrome Respiratória Aguda Grave/fisiopatologia
12.
Mol Immunol ; 125: 70-82, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32652362

RESUMO

Immune responses and central nervous system dysfunction are two main factors to be considered during rabies virus (RABV) infection. However, the mechanisms by which RABV strains of different virulence regulate with chemokine expression and the signaling pathways responsible for the immune responses in the terminal stage of infection both in vivo and in vitro have not been fully elucidated. In this study, we found low expression levels of proinflammatory chemokines in the mouse brain upon infection with street RABV strains (CXZ17 and HN10) at the late stage of infection. We also examined the difference in inflammatory response upon infection with RABV strains of different virulence in a mouse model. We found that the expression of proinflammatory chemokines increased to a varying degree upon infection with street RABV (CXZ17 and HN10) or laboratory-fixed RABV (CVS-11, aG, and CTN); CXCL10, CCL5, and CCL2 were the most significantly upregulated chemokines in brain tissue and microglial BV-2 cells in response to infection with RABV strains of different virulence. Our data also demonstrate significant activation of the MAPK and NF-κB pathways in mouse brain tissue at the late stage of RABV infection. We also found (i) low phosphorylation signals of MAPK and NF-κB p65 in neuronal cells upon infection with CXZ17 and HN10 in the mouse brain and (ii) strong phosphorylation signals in cerebrovascular endothelial cells and neuronal cells upon CTN or aG infection. Moreover, we quantified the nuclear localization status of MAPK signals and NF-κB p65 upon infection with CVS-11, aG, and CTN in BV-2 cells in vitro. We also found (i) that the activation of the p38, ERK1/2, and NF-κB p65 pathway, which stimulates CXCL10, CCL5, and CCL2 expression upon infection with RABV strains of different virulence (aG, CTN, and CVS-11), is triggered after virus entry into BV-2 cells and (ii) that the expression of CXCL10, CCL5, and CCL2 is required for the activation of NF-κB, p38, and ERK1/2, but not JNK. Overall, our study provides insight into the regulation of inflammatory responses mediated by MAPK and NF-κB in the mouse brain and in microglial cells upon RABV infection of different virulence.


Assuntos
Encéfalo/virologia , Inflamação/virologia , Sistema de Sinalização das MAP Quinases/imunologia , NF-kappa B/imunologia , Vírus da Raiva/patogenicidade , Raiva/imunologia , Animais , Encéfalo/imunologia , Inflamação/imunologia , Camundongos , Microglia/imunologia , Microglia/virologia , Vírus da Raiva/imunologia , Virulência/imunologia
13.
J Neural Transm (Vienna) ; 127(9): 1217-1228, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32725545

RESUMO

While there is abounding literature on virus-induced pathology in general and coronavirus in particular, recent evidence accumulates showing distinct and deleterious brain affection. As the respiratory tract connects to the brain without protection of the blood-brain barrier, SARS-CoV-2 might in the early invasive phase attack the cardiorespiratory centres located in the medulla/pons areas, giving rise to disturbances of respiration and cardiac problems. Furthermore, brainstem regions are at risk to lose their functional integrity. Therefore, long-term neurological as well as psychiatric symptomatology and eventual respective disorders cannot be excluded as evidenced from influenza-A triggered post-encephalitic Parkinsonism and HIV-1 triggered AIDS-dementia complex. From the available evidences for coronavirus-induced brain pathology, this review concludes a number of unmet needs for further research strategies like human postmortem brain analyses. SARS-CoV-2 mirroring experimental animal brain studies, characterization of time-dependent and region-dependent spreading behaviours of coronaviruses, enlightening of pathological mechanisms after coronavirus infection using long-term animal models and clinical observations of patients having had COVID-19 infection are calling to develop both protective strategies and drug discoveries to avoid early and late coronavirus-induced functional brain disturbances, symptoms and eventually disorders. To fight SARS-CoV-2, it is an urgent need to enforce clinical, molecular biological, neurochemical and genetic research including brain-related studies on a worldwide harmonized basis.


Assuntos
Betacoronavirus , Encéfalo/patologia , Infecções por Coronavirus/patologia , Diagnóstico , Pneumonia Viral/patologia , Barreira Hematoencefálica/patologia , Barreira Hematoencefálica/virologia , Encéfalo/virologia , Técnicas e Procedimentos Diagnósticos/tendências , Humanos , Pandemias , Fatores de Tempo
14.
J Stroke Cerebrovasc Dis ; 29(8): 104941, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32689643

RESUMO

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global health threat. Some COVID-19 patients have exhibited widespread neurological manifestations including stroke. Acute ischemic stroke, intracerebral hemorrhage, and cerebral venous sinus thrombosis have been reported in patients with COVID-19. COVID-19-associated coagulopathy is increasingly recognized as a result of acute infection and is likely caused by inflammation, including inflammatory cytokine storm. Recent studies suggest that axonal transport of SARS-CoV-2 to the brain can occur via the cribriform plate adjacent to the olfactory bulb that may lead to symptomatic anosmia. The internalization of SARS-CoV-2 is mediated by the binding of the spike glycoprotein of the virus to the angiotensin-converting enzyme 2 (ACE2) on cellular membranes. ACE2 is expressed in several tissues including lung alveolar cells, gastrointestinal tissue, and brain. The aim of this review is to provide insights into the clinical manifestations and pathophysiological mechanisms of stroke in COVID-19 patients. SARS-CoV-2 can down-regulate ACE2 and, in turn, overactivate the classical renin-angiotensin system (RAS) axis and decrease the activation of the alternative RAS pathway in the brain. The consequent imbalance in vasodilation, neuroinflammation, oxidative stress, and thrombotic response may contribute to the pathophysiology of stroke during SARS-CoV-2 infection.


Assuntos
Betacoronavirus/patogenicidade , Encéfalo/fisiopatologia , Infecções por Coronavirus/fisiopatologia , Encefalite Viral/fisiopatologia , Pneumonia Viral/fisiopatologia , Acidente Vascular Cerebral/fisiopatologia , Betacoronavirus/metabolismo , Coagulação Sanguínea , Encéfalo/metabolismo , Encéfalo/virologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/metabolismo , Infecções por Coronavirus/virologia , Encefalite Viral/epidemiologia , Encefalite Viral/metabolismo , Encefalite Viral/virologia , Interações entre Hospedeiro e Microrganismos , Humanos , Mediadores da Inflamação/metabolismo , Estresse Oxidativo , Pandemias , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/epidemiologia , Pneumonia Viral/metabolismo , Pneumonia Viral/virologia , Sistema Renina-Angiotensina , Transdução de Sinais , Glicoproteína da Espícula de Coronavírus/metabolismo , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/metabolismo , Acidente Vascular Cerebral/virologia , Vasodilatação , Virulência
15.
Proc Natl Acad Sci U S A ; 117(32): 19465-19474, 2020 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-32709745

RESUMO

Infection by malaria parasites triggers dynamic immune responses leading to diverse symptoms and pathologies; however, the molecular mechanisms responsible for these reactions are largely unknown. We performed Trans-species Expression Quantitative Trait Locus analysis to identify a large number of host genes that respond to malaria parasite infections. Here we functionally characterize one of the host genes called receptor transporter protein 4 (RTP4) in responses to malaria parasite and virus infections. RTP4 is induced by type I IFN (IFN-I) and binds to the TANK-binding kinase (TBK1) complex where it negatively regulates TBK1 signaling by interfering with expression and phosphorylation of both TBK1 and IFN regulatory factor 3. Rtp4 -/- mice were generated and infected with malaria parasite Plasmodiun berghei ANKA. Significantly higher levels of IFN-I response in microglia, lower parasitemia, fewer neurologic symptoms, and better survival rates were observed in Rtp4 -/- than in wild-type mice. Similarly, RTP4 deficiency significantly reduced West Nile virus titers in the brain, but not in the heart and the spleen, of infected mice, suggesting a specific role for RTP4 in brain infection and pathology. This study reveals functions of RTP4 in IFN-I response and a potential target for therapy in diseases with neuropathology.


Assuntos
Encéfalo/patologia , Interferon Tipo I/metabolismo , Malária Cerebral/patologia , Chaperonas Moleculares/metabolismo , Animais , Encéfalo/parasitologia , Encéfalo/virologia , Células HEK293 , Interações Hospedeiro-Patógeno , Humanos , Fator Regulador 3 de Interferon , Malária Cerebral/metabolismo , Malária Cerebral/parasitologia , Proteínas de Membrana , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microglia/metabolismo , Chaperonas Moleculares/genética , Fosforilação , Plasmodium berghei/fisiologia , Plasmodium yoelii/fisiologia , Ligação Proteica , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais , Febre do Nilo Ocidental/metabolismo , Febre do Nilo Ocidental/patologia , Febre do Nilo Ocidental/virologia , Vírus do Nilo Ocidental/fisiologia
16.
Eur J Nucl Med Mol Imaging ; 47(11): 2487-2492, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32700058
17.
Neurol Sci ; 41(10): 2657-2669, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32725449

RESUMO

Respiratory viruses are opportunistic pathogens that infect the upper respiratory tract in humans and cause severe illnesses, especially in vulnerable populations. Some viruses have neuroinvasive properties and activate the immune response in the brain. These immune events may be neuroprotective or they may cause long-term damage similar to what is seen in some neurodegenerative diseases. The new "Severe Acute Respiratory Syndrome Coronavirus 2" (SARS-CoV-2) is one of the Respiratory viruses causing highly acute lethal pneumonia coronavirus disease 2019 (COVID-19) with clinical similarities to those reported in "Severe Acute Respiratory Syndrome Coronavirus"(SARS-CoV) and the "Middle East Respiratory Syndrome Coronavirus"(MERS-CoV) including neurological manifestation. To examine the possible neurological damage induced by SARS-CoV-2, it is necessary to understand the immune reactions to viral infection in the brain, and their short- and long-term consequences. Considering the similarities between SARS-CoV and SARS-CoV-2, which will be discussed, cooperative homological and phylogenetical studies lead us to question if SARS-CoV-2 can have similar neuroinvasive capacities and neuroinflammatiory events that may lead to the same short- and long-term neuropathologies that SARS-CoV had shown in human and animal models. To explain the neurological manifestation caused by SARS-CoV-2, we will present a literature review of 765 COVID-19 patients, in which 18% had neurological symptoms and complications, including encephalopathy, encephalitis and cerebrovascular pathologies, acute myelitis, and Guillain-Barré syndrome. Clinical studies describe anosmia or partial loss of the sense of smell as the most frequent symptom in COVID19 patients, suggesting that olfactory dysfunction and the initial ultrarapid immune responses could be a prognostic factor.


Assuntos
Betacoronavirus , Encéfalo/virologia , Infecções por Coronavirus/complicações , Doenças do Sistema Nervoso/etiologia , Doenças do Sistema Nervoso/virologia , Pneumonia Viral/complicações , Nervo Vago/virologia , Barreira Hematoencefálica/patologia , Barreira Hematoencefálica/virologia , Encéfalo/patologia , Infecções por Coronavirus/patologia , Humanos , Doenças do Sistema Nervoso/patologia , Pandemias , Pneumonia Viral/patologia , Nervo Vago/patologia
18.
Neurosci Res ; 158: 1-5, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32628969

RESUMO

Coronaviruses (CoVs) are large positive stranded enveloped RNA viruses that generally cause enteric and respiratory diseases in humans and in animals. Most human CoVs have recently attracted global attention to their lethal potential and great infectious capacity. A highly pathogenic CoV, called COVID-19 or SARS-CoV-2, dramatically emerged in December 2019 in Wuhan, China. This new CoV has caused severe pneumonia in China and rapidly spreads around the world, the COVID-19 pandemic. Growing evidence pieces show that viruses, such as CoVs, can enter the central nervous system from different pathways and inducing neurotoxicity. Therefore, it is urgent to make clear whether SARS-CoV-2 has access to the central nervous system and can cause direct neuronal effects. Moreover, a brain-lung-brain axis is been proposed from the scientific community where severe neurological dysfunction and injury are associated with lung injury, and vice versa. In this axis, virus-induced inflammation and oxidative stress could be the common mechanisms responsible for CoV neurological symptoms. Therefore, is important to make clear whether SARS-CoV-2 lung damage can cause direct or indirect neuronal effects.


Assuntos
Encéfalo/virologia , Infecções por Coronavirus , Pandemias , Pneumonia Viral , Animais , Betacoronavirus , Sistema Nervoso Central/virologia , Infecções por Coronavirus/patologia , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/virologia , Humanos , Pneumonia Viral/patologia , Pneumonia Viral/fisiopatologia , Pneumonia Viral/virologia
19.
Lancet HIV ; 7(7): e504-e513, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32621876

RESUMO

High rates of cognitive disorders in antiretroviral-treated people living with HIV have been described worldwide. The exact prevalence of such cognitive disorders is determined by the definitions used, and the presence of these cognitive disorders significantly impacts the overall wellbeing of people with HIV. With the cohort of people with HIV becoming increasingly older, and having high rates of comorbidities and concomitant medication use, rates of cognitive disorders are likely to increase. Conversely, interventions are being sought to reduce the size of the latent HIV reservoir. If successful, such interventions are likely to also reduce the HIV reservoir in the brain compartment, which could result in improvements in cognitive function and reduced rates of impairment.


Assuntos
Antirretrovirais/uso terapêutico , Transtornos Cognitivos/epidemiologia , Infecções por HIV/complicações , Encéfalo/virologia , Cognição , Transtornos Cognitivos/complicações , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/prevenção & controle , Estudos de Coortes , Comorbidade , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Humanos , Prevalência , Latência Viral
20.
ACS Chem Neurosci ; 11(15): 2361-2369, 2020 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-32627524

RESUMO

Spike protein (S protein) is the virus "key" to infect cells and is able to strongly bind to the human angiotensin-converting enzyme2 (ACE2), as has been reported. In fact, Spike structure and function is known to be highly important for cell infection as well as for entering the brain. Growing evidence indicates that different types of coronaviruses not only affect the respiratory system, but they might also invade the central nervous system (CNS). However, very little evidence has been so far reported on the presence of COVID-19 in the brain, and the potential exploitation, by this virus, of the lung to brain axis to reach neurons has not been completely understood. In this Article, we assessed the SARS-CoV and SARS-CoV-2 Spike protein sequence, structure, and electrostatic potential using computational approaches. Our results showed that the S proteins of SARS-CoV-2 and SARS-CoV are highly similar, sharing a sequence identity of 77%. In addition, we found that the SARS-CoV-2 S protein is slightly more positively charged than that of SARS-CoV since it contains four more positively charged residues and five less negatively charged residues which may lead to an increased affinity to bind to negatively charged regions of other molecules through nonspecific and specific interactions. Analysis the S protein binding to the host ACE2 receptor showed a 30% higher binding energy for SARS-CoV-2 than for the SARS-CoV S protein. These results might be useful for understanding the mechanism of cell entry, blood-brain barrier crossing, and clinical features related to the CNS infection by SARS-CoV-2.


Assuntos
Betacoronavirus/genética , Encéfalo/virologia , Infecções por Coronavirus/genética , Doenças do Sistema Nervoso/genética , Doenças do Sistema Nervoso/virologia , Pneumonia Viral/genética , Glicoproteína da Espícula de Coronavírus/genética , Sequência de Aminoácidos , Betacoronavirus/química , Humanos , Pandemias , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína , Glicoproteína da Espícula de Coronavírus/química
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