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1.
Medicina (Kaunas) ; 57(4)2021 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-33806100

RESUMEN

In the last two decades, three unknown pathogens have caused outbreaks, generating severe global health concerns. In 2003, after nucleic acid genotyping, a new virus was named severe acute respiratory syndrome coronavirus (SARS-CoV). After nine years, another coronavirus emerged in the middle east and was named MERS-CoV (Middle East Respiratory Syndrome-Coronavirus). Finally, in December 2019, a new unknown coronavirus was isolated from a cluster of patients and was named SARS-CoV-2 (COVID-19, coronavirus disease 2019). This review aims to propose a complete overview of autopsy in the three coronaviruses over the past two decades, showing its pivotal role in the management of unknown diseases. A total of 116 studies fulfilled the inclusion criteria: 14 studies were collected concerning SARS-CoV (87 autopsy reports, from Asian and American countries), 2 studies for MERS-CoV (2 autopsy reports, from Middle-East Asian countries), and 100 studies on SARS-CoV-2 (930 autopsy reports). Analyzing the data obtained on COVID-19, based on the country criterion, a large number of post-mortem investigation were performed in European countries (580 reports), followed by American countries (251 reports). It is interesting to note that no data were found from the Oceanic countries, maybe because of the minor involvement of the outbreak. In all cases, autopsy provided much information about each unknown coronavirus. Despite advanced technologies in the diagnostic fields, to date, autopsy remains the gold standard method to understand the biological features and the pathogenesis of unknown infections, especially when awareness of a pathogen is restricted and the impact on the healthcare system is substantial. The knowledge gained through this technique may positively influence therapeutic strategies, ultimately reducing mortality.


Asunto(s)
COVID-19/patología , Síndrome Respiratorio Agudo Grave/patología , Autopsia , Infecciones por Coronavirus/patología , Humanos , Coronavirus del Síndrome Respiratorio de Oriente Medio , Virus del SRAS , SARS-CoV-2
2.
Cell Transplant ; 30: 963689721993769, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33840257

RESUMEN

Until July 29th, the number of confirmed coronavirus (COVID-19) cases worldwide has risen to over 16 million, within which 655 k deaths. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) emerges as the 11th global pandemic disease, showing the highest infectivity and lowest infection fatality rate. In this review, we compare the immunopathology among SARS-CoV, Middle East respiratory syndrome coronavirus, and SARS-CoV2. SARS-CoV2 is similar to SARS-CoV; it can cause lymphocytopenia and a rising granulocyte count. Here we point out the human body and concentrated society make for an excellent incubator for virus evolution. Most research energies put into developing the SARS-CoV2 vaccine are trying to block virus infection. Sixty-five percent of severe patients die with multiple organ failure, inflammation, and cytokine storm, which indicates that the patient's immune system maintains functionality. Finding a way to trigger the specific T cell subset and plasmablast in our body is the best shot to get away with SARS-CoV2.


Asunto(s)
COVID-19/inmunología , SARS-CoV-2/inmunología , Animales , COVID-19/patología , Coronavirus/inmunología , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/patología , Síndrome de Liberación de Citoquinas/inmunología , Síndrome de Liberación de Citoquinas/patología , Humanos , Inflamación/inmunología , Inflamación/patología , Virus del SRAS/inmunología , Síndrome Respiratorio Agudo Grave/inmunología , Síndrome Respiratorio Agudo Grave/patología
3.
J Virol ; 95(12)2021 05 24.
Artículo en Inglés | MEDLINE | ID: mdl-33762411

RESUMEN

Porcine hemagglutinating encephalomyelitis virus (PHEV) is a betacoronavirus that causes vomiting and wasting disease and/or encephalomyelitis in suckling pigs. This study characterized PHEV infection, pathogenesis, and immune response in cesarean-derived, colostrum-deprived (CDCD) neonatal pigs. Infected animals developed mild respiratory, enteric, and neurological clinical signs between 2 to 13 days postoronasal inoculation (dpi). PHEV did not produce viremia, but virus shedding was detected in nasal secretions (1 to 10 dpi) and feces (2 to 7 dpi) by reverse transcriptase quantitative PCR (RT-qPCR). Viral RNA was detected in all tissues except liver, but the detection rate and RT-qPCR threshold cycle (CT ) values decreased over time. The highest concentration of virus was detected in inoculated piglets necropsied at 5 dpi in turbinate and trachea, followed by tonsils, lungs, tracheobronchial lymph nodes, and stomach. The most representative microscopic lesions were gastritis lymphoplasmacytic, moderate, multifocal, with perivasculitis, and neuritis with ganglia degeneration. A moderate inflammatory response, characterized by increased levels of interferon alpha (IFN-α) in plasma (5 dpi) and infiltration of T lymphocytes and macrophages were also observed. Increased plasma levels of interleukin-8 (IL-8) were detected at 10 and 15 dpi, coinciding with the progressive resolution of the infection. Moreover, a robust antibody response was detected by 10 dpi. An ex vivo air-liquid CDCD-derived porcine respiratory cells culture (ALI-PRECs) system showed virus replication in ALI-PRECs and cytopathic changes and disruption of ciliated columnar epithelia, thereby confirming the tracheal epithelia as a primary site of infection for PHEV.IMPORTANCE Among the ∼46 virus species in the family Coronaviridae, many of which are important pathogens of humans and 6 of which are commonly found in pigs, porcine hemagglutinating encephalomyelitis remains one of the least researched. The present study provided a comprehensive characterization of the PHEV infection process and immune responses using CDCD neonatal pigs. Moreover, we used an ex vivo ALI-PRECs system resembling the epithelial lining of the tracheobronchial region of the porcine respiratory tract to demonstrate that the upper respiratory tract is a primary site of PHEV infection. This study provides a platform for further multidisciplinary studies of coronavirus infections.


Asunto(s)
Betacoronavirus 1/inmunología , Infecciones por Coronavirus/inmunología , Interferón-alfa/inmunología , Interleucina-8/inmunología , Enfermedades de los Porcinos/inmunología , Linfocitos T/inmunología , Animales , Línea Celular , Infecciones por Coronavirus/patología , Infecciones por Coronavirus/veterinaria , Especificidad de Órganos/inmunología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Porcinos , Enfermedades de los Porcinos/patología , Linfocitos T/patología , Linfocitos T/virología
4.
Sci Rep ; 11(1): 7132, 2021 03 30.
Artículo en Inglés | MEDLINE | ID: mdl-33785846

RESUMEN

The objective of this study was to test the effectiveness of ivermectin for the treatment of mouse hepatitis virus (MHV), a type 2 family RNA coronavirus similar to SARS-CoV-2. Female BALB/cJ mice were infected with 6,000 PFU of MHV-A59 (group infected, n = 20) or infected and then immediately treated with a single dose of 500 µg/kg ivermectin (group infected + IVM, n = 20) or were not infected and treated with PBS (control group, n = 16). Five days after infection/treatment, the mice were euthanized and the tissues were sampled to assess their general health status and infection levels. Overall, the results demonstrated that viral infection induced typical MHV-caused disease, with the livers showing severe hepatocellular necrosis surrounded by a severe lymphoplasmacytic inflammatory infiltration associated with a high hepatic viral load (52,158 AU), while mice treated with ivermectin showed a better health status with a lower viral load (23,192 AU; p < 0.05), with only a few having histopathological liver damage (p < 0.05). No significant differences were found between the group infected + IVM and control group mice (P = NS). Furthermore, serum transaminase levels (aspartate aminotransferase and alanine aminotransferase) were significantly lower in the treated mice than in the infected animals. In conclusion, ivermectin diminished the MHV viral load and disease in the mice, being a useful model for further understanding this therapy against coronavirus diseases.


Asunto(s)
Antivirales/farmacología , Infecciones por Coronavirus/tratamiento farmacológico , Ivermectina/farmacología , Animales , Antivirales/administración & dosificación , Peso Corporal/efectos de los fármacos , Infecciones por Coronavirus/patología , Infecciones por Coronavirus/virología , Modelos Animales de Enfermedad , Femenino , Ivermectina/administración & dosificación , Riñón/efectos de los fármacos , Riñón/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Hígado/virología , Ratones Endogámicos BALB C , Monocitos/efectos de los fármacos , Virus de la Hepatitis Murina/patogenicidad , Neutrófilos/efectos de los fármacos , Proteínas/metabolismo , Transaminasas/metabolismo , Factor de Necrosis Tumoral alfa/sangre , Carga Viral/efectos de los fármacos
5.
Eur J Immunol ; 51(5): 1062-1070, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33687066

RESUMEN

Coronaviruses (CoVs) represent enveloped, ss RNA viruses with the ability to infect a range of vertebrates causing mainly lung, CNS, enteric, and hepatic disease. While the infection with human CoV is commonly associated with mild respiratory symptoms, the emergence of SARS-CoV, MERS-CoV, and SARS-CoV-2 highlights the potential for CoVs to cause severe respiratory and systemic disease. The devastating global health burden caused by SARS-CoV-2 has spawned countless studies seeking clinical correlates of disease severity and host susceptibility factors, revealing a complex network of antiviral immune circuits. The mouse hepatitis virus (MHV) is, like SARS-CoV-2, a beta-CoV and is endemic in wild mice. Laboratory MHV strains have been extensively studied to reveal coronavirus virulence factors and elucidate host mechanisms of antiviral immunity. These are reviewed here with the aim to identify translational insights for SARS-CoV-2 learned from murine CoVs.


Asunto(s)
Inmunidad Adaptativa/inmunología , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/patología , Virus de la Hepatitis Murina/inmunología , Virus de la Hepatitis Murina/patogenicidad , Animales , Modelos Animales de Enfermedad , Humanos , Ratones , Coronavirus del Síndrome Respiratorio de Oriente Medio/inmunología , Virus del SRAS/inmunología , SARS-CoV-2/inmunología , Índice de Severidad de la Enfermedad , Glicoproteína de la Espiga del Coronavirus/metabolismo , Tropismo Viral/fisiología
6.
Diagn Microbiol Infect Dis ; 100(2): 115338, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33610036

RESUMEN

We show that individuals with documented history of seasonal coronavirus have a similar SARS-CoV-2 infection rate and COVID-19 severity as those with no prior history of seasonal coronavirus. Our findings suggest prior infection with seasonal coronavirus does not provide immunity to subsequent infection with SARS-CoV-2.


Asunto(s)
COVID-19/epidemiología , Infecciones por Coronavirus/epidemiología , COVID-19/inmunología , COVID-19/patología , COVID-19/virología , Coronavirus/inmunología , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/patología , Infecciones por Coronavirus/virología , Reacciones Cruzadas/inmunología , Humanos , Reacción en Cadena de la Polimerasa , Estudios Retrospectivos , SARS-CoV-2/inmunología , Estaciones del Año , Índice de Severidad de la Enfermedad
7.
J Neurovirol ; 27(2): 197-216, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33547593

RESUMEN

The pandemic caused by SARS-CoV-2 has caused widespread infection and significant mortality across the globe. Combined virology perspective of SARS-CoV-2 with a deep-rooted understanding of pathophysiological and immunological processes underlying the clinical manifestations of COVID-19 is of prime importance. The characteristic symptom of COVID-19 is respiratory distress with diffused alveolar damage, but emerging evidence suggests COVID-19 might also have neurologic consequences. Dysregulated homeostasis in the lungs has proven to be fatal, but one cannot ignore that the inability to breathe might be due to defects in the respiratory control center of the brainstem. While the mechanism of pulmonary distress has been documented in the literature, awareness of neurological features and their pathophysiology is still in the nascent state. This review makes references to the neuro-immune axis and neuro-invasive potential of SARS-CoV and SARS-CoV2, as well as the prototypic H-CoV strains in human brains. Simultaneously, considerable discussion on relevant experimental evidence of mild to severe neurological manifestations of fellow neurotropic murine-ß-CoVs (m-CoVs) in the mouse model will help understand the underpinning mechanisms of Neuro-COVID. In this review, we have highlighted the neuroimmunopathological processes in murine CoVs. While MHV infection in mice and SARS-CoV-2 infection in humans share numerous parallels, there are critical differences in viral recognition and viral entry. These similarities are highlighted in this review, while differences have also been emphasized. Though CoV-2 Spike does not favorably interact with murine ACE2 receptor, modification of murine SARS-CoV2 binding domain or development of transgenic ACE-2 knock-in mice might help in mediating consequential infection and understanding human CoV2 pathogenesis in murine models. While a global animal model that can replicate all aspects of the human disease remains elusive, prior insights and further experiments with fellow m-ß-CoV-induced cause-effect experimental models and current human COVID-19 patients data may help to mitigate the SARS-CoV-2-induced multifactorial multi-organ failure.


Asunto(s)
COVID-19/patología , Modelos Animales de Enfermedad , Virus de la Hepatitis Murina/patogenicidad , Neuroinmunomodulación/fisiología , Animales , COVID-19/inmunología , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/patología , Humanos , Ratones , Virus de la Hepatitis Murina/inmunología , SARS-CoV-2
8.
J Virol ; 95(9)2021 04 12.
Artículo en Inglés | MEDLINE | ID: mdl-33568512

RESUMEN

Porcine epidemic diarrhea virus (PEDV) is an α-coronavirus causing severe diarrhea and high mortality rates in suckling piglets and posing significant economic impact. PEDV replication is completed and results in a large amount of RNA in the cytoplasm. Stress granules (SGs) are dynamic cytosolic RNA granules formed under various stress conditions, including viral infections. Several previous studies suggested that SGs were involved in the antiviral activity of host cells to limit viral propagation. However, the underlying mechanisms are poorly understood. This study aimed to delineate the molecular mechanisms regulating the SG response to PEDV infection. SG formation is induced early during PEDV infection, but as infection proceeds, this ability is lost and SGs disappear at late stages of infection (>18 h postinfection). PEDV infection resulted in the cleavage of Ras-GTPase-activating protein-binding protein 1 (G3BP1) mediated by caspase-8. Using mutational analysis, the PEDV-induced cleavage site within G3BP1 was identified, which differed from the 3C protease cleavage site previously identified. Furthermore, G3BP1 cleavage by caspase-8 at D168 and D169 was confirmed in vitro as well as in vivo The overexpression of cleavage-resistant G3BP1 conferred persistent SG formation and suppression of viral replication. Additionally, the knockdown of endogenous G3BP1 abolished SG formation and potentiated viral replication. Taken together, these data provide new insights into novel strategies in which PEDV limits the host stress response and antiviral responses and indicate that caspase-8-mediated G3BP1 cleavage is important in the failure of host defense against PEDV infection.IMPORTANCE Coronaviruses (CoVs) are drawing extensive attention again since the outbreaks of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2019. CoVs are prone to variation and own the transmission capability by crossing the species barrier resulting in reemergence. How CoVs manipulate the antiviral responses of their hosts needs to be explored. Overall, the study provides new insight into how porcine epidemic diarrhea virus (PEDV) impaired SG assembly by targeting G3BP1 via the host proteinase caspase-8. These findings enhanced the understanding of PEDV infection and might help identify new antiviral targets that could inhibit viral replication and limit the pathogenesis of PEDV.


Asunto(s)
Caspasa 8/metabolismo , Infecciones por Coronavirus/metabolismo , Gránulos Citoplasmáticos/metabolismo , Virus de la Diarrea Epidémica Porcina/fisiología , Proteolisis , Proteínas con Motivos de Reconocimiento de ARN/metabolismo , Replicación Viral , Animales , Caspasa 8/genética , Chlorocebus aethiops , Infecciones por Coronavirus/genética , Infecciones por Coronavirus/patología , Gránulos Citoplasmáticos/genética , Gránulos Citoplasmáticos/virología , Células HEK293 , Humanos , Proteínas con Motivos de Reconocimiento de ARN/genética , Porcinos , Células Vero
9.
PLoS One ; 16(2): e0245072, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33534822

RESUMEN

Middle East respiratory syndrome (MERS-COV), first identified in Saudi Arabia, was caused by a novel strain of coronavirus. Outbreaks were recorded from different regions of the world, especially South Korea and the Middle East, and were correlated with a 35% mortality rate. MERS-COV is a single-stranded, positive RNA virus that reaches the host by binding to the receptor of dipeptidyl-peptides. Because of the unavailability of the vaccine available for the protection from MERS-COV infection, the rapid case detection, isolation, infection prevention has been recommended to combat MERS-COV infection. So, vaccines for the treatment of MERS-COV infection need to be developed urgently. A possible antiviral mechanism for preventing MERS-CoV infection has been considered to be MERS-CoV vaccines that elicit unique T-cell responses. In the present study, we incorporated both molecular docking and immunoinformatic approach to introduce a multiepitope vaccine (MEP) against MERS-CoV by selecting 15 conserved epitopes from seven viral proteins such as three structural proteins (envelope, membrane, and nucleoprotein) and four non-structural proteins (ORF1a, ORF8, ORF3, ORF4a). The epitopes, which were examined for non-homologous to host and antigenicity, were selected on the basis of conservation between T-cell, B-cell, and IFN-γ epitopes. The selected epitopes were then connected to the adjuvant (ß-defensin) at the N-terminal through an AAY linker to increase the immunogenic potential. Structural modelling and physiochemical characteristic were applied to the vaccine construct developed. Afterwards the structure has been successfully docked with antigenic receptor, Toll-like receptor 3 (TLR-3) and in-silico cloning ensures that its expression efficiency is legitimate. Nonetheless the MEP presented needs tests to verify its safety and immunogenic profile.


Asunto(s)
Epítopos/inmunología , Coronavirus del Síndrome Respiratorio de Oriente Medio/metabolismo , Proteoma , Vacunas Virales/inmunología , Secuencia de Aminoácidos , Sitios de Unión , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/patología , Infecciones por Coronavirus/prevención & control , Diseño de Fármacos , Epítopos/química , Humanos , Simulación del Acoplamiento Molecular , Estructura Secundaria de Proteína , Estructura Terciaria de Proteína , Vacunas de Subunidad/química , Vacunas de Subunidad/inmunología , Proteínas no Estructurales Virales/química , Proteínas no Estructurales Virales/inmunología , Proteínas Estructurales Virales/química , Proteínas Estructurales Virales/inmunología , Vacunas Virales/química
10.
PLoS One ; 16(2): e0246150, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33534852

RESUMEN

A coronavirus pandemic caused by a novel coronavirus (SARS-CoV-2) has spread rapidly worldwide since December 2019. Improved understanding and new strategies to cope with novel coronaviruses are urgently needed. Viruses (especially RNA viruses) encode a limited number and size (length of polypeptide chain) of viral proteins and must interact with the host cell components to control (hijack) the host cell machinery. To achieve this goal, the extensive mimicry of SLiMs in host proteins provides an effective strategy. However, little is known regarding SLiMs in coronavirus proteins and their potential targets in host cells. The objective of this study is to uncover SLiMs in coronavirus proteins that are present within host cells. These SLiMs have a high possibility of interacting with host intracellular proteins and hijacking the host cell machinery for virus replication and dissemination. In total, 1,479 SLiM hits were identified in the 16 proteins of 590 coronaviruses infecting humans. Overall, 106 host proteins were identified that may interact with SLiMs in 16 coronavirus proteins. These SLiM-interacting proteins are composed of many intracellular key regulators, such as receptors, transcription factors and kinases, and may have important contributions to virus replication, immune evasion and viral pathogenesis. A total of 209 pathways containing proteins that may interact with SLiMs in coronavirus proteins were identified. This study uncovers potential mechanisms by which coronaviruses hijack the host cell machinery. These results provide potential therapeutic targets for viral infections.


Asunto(s)
Infecciones por Coronavirus/patología , Coronavirus del Síndrome Respiratorio de Oriente Medio/metabolismo , Virus del SRAS/metabolismo , SARS-CoV-2/metabolismo , Proteínas Virales/metabolismo , Secuencias de Aminoácidos , Infecciones por Coronavirus/virología , Bases de Datos de Proteínas , Humanos , Coronavirus del Síndrome Respiratorio de Oriente Medio/aislamiento & purificación , Filogenia , Dominios y Motivos de Interacción de Proteínas , Proteínas/química , Proteínas/clasificación , Virus del SRAS/aislamiento & purificación , SARS-CoV-2/aislamiento & purificación , Transducción de Señal/genética , Interfaz Usuario-Computador , Proteínas Virales/química , Proteínas Virales/clasificación
11.
Int J Mol Sci ; 22(3)2021 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-33525632

RESUMEN

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is a novel epidemic strain of Betacoronavirus that is responsible for the current viral pandemic, coronavirus disease 2019 (COVID-19), a global health crisis. Other epidemic Betacoronaviruses include the 2003 SARS-CoV-1 and the 2009 Middle East Respiratory Syndrome Coronavirus (MERS-CoV), the genomes of which, particularly that of SARS-CoV-1, are similar to that of the 2019 SARS-CoV-2. In this extensive review, we document the most recent information on Coronavirus proteins, with emphasis on the membrane proteins in the Coronaviridae family. We include information on their structures, functions, and participation in pathogenesis. While the shared proteins among the different coronaviruses may vary in structure and function, they all seem to be multifunctional, a common theme interconnecting these viruses. Many transmembrane proteins encoded within the SARS-CoV-2 genome play important roles in the infection cycle while others have functions yet to be understood. We compare the various structural and nonstructural proteins within the Coronaviridae family to elucidate potential overlaps and parallels in function, focusing primarily on the transmembrane proteins and their influences on host membrane arrangements, secretory pathways, cellular growth inhibition, cell death and immune responses during the viral replication cycle. We also offer bioinformatic analyses of potential viroporin activities of the membrane proteins and their sequence similarities to the Envelope (E) protein. In the last major part of the review, we discuss complement, stimulation of inflammation, and immune evasion/suppression that leads to CoV-derived severe disease and mortality. The overall pathogenesis and disease progression of CoVs is put into perspective by indicating several stages in the resulting infection process in which both host and antiviral therapies could be targeted to block the viral cycle. Lastly, we discuss the development of adaptive immunity against various structural proteins, indicating specific vulnerable regions in the proteins. We discuss current CoV vaccine development approaches with purified proteins, attenuated viruses and DNA vaccines.


Asunto(s)
Betacoronavirus/fisiología , Infecciones por Coronavirus/metabolismo , Proteínas de la Matriz Viral/metabolismo , Animales , Betacoronavirus/genética , Betacoronavirus/inmunología , COVID-19/inmunología , COVID-19/metabolismo , COVID-19/patología , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/patología , Genoma Viral , Interacciones Huésped-Patógeno , Humanos , Evasión Inmune , Mapas de Interacción de Proteínas , SARS-CoV-2/genética , SARS-CoV-2/inmunología , SARS-CoV-2/fisiología , Proteínas de la Matriz Viral/genética , Proteínas de la Matriz Viral/inmunología , Internalización del Virus , Replicación Viral
12.
Life Sci ; 272: 119245, 2021 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-33609539

RESUMEN

In the past 20 years, infections caused by coronaviruses SARS-CoV, MERS-CoV and SARS-CoV-2 have posed a threat to public health since they may cause severe acute respiratory syndrome (SARS) in humans. The Complement System is activated during viral infection, being a central protagonist of innate and acquired immunity. Here, we report some interactions between these three coronaviruses and the Complement System, highlighting the central role of C3 with the severity of these infections. Although it can be protective, its role during coronavirus infections seems to be contradictory. For example, during SARS-CoV-2 infection, Complement System can control the viral infection in asymptomatic or mild cases; however, it can also intensify local and systemic damage in some of severe COVID-19 patients, due to its potent proinflammatory effect. In this last condition, the activation of the Complement System also amplifies the cytokine storm and the pathogenicity of coronavirus infection. Experimental treatment with Complement inhibitors has been an enthusiastic field of intense investigation in search of a promising additional therapy in severe COVID-19 patients.


Asunto(s)
COVID-19/inmunología , Proteínas del Sistema Complemento/inmunología , SARS-CoV-2/inmunología , Animales , COVID-19/complicaciones , COVID-19/tratamiento farmacológico , COVID-19/patología , Activación de Complemento/efectos de los fármacos , Complemento C3/inmunología , Inactivadores del Complemento/farmacología , Inactivadores del Complemento/uso terapéutico , Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/patología , Síndrome de Liberación de Citoquinas/complicaciones , Síndrome de Liberación de Citoquinas/tratamiento farmacológico , Síndrome de Liberación de Citoquinas/inmunología , Síndrome de Liberación de Citoquinas/patología , Humanos , Inflamación/complicaciones , Inflamación/tratamiento farmacológico , Inflamación/inmunología , Inflamación/patología , Coronavirus del Síndrome Respiratorio de Oriente Medio/inmunología , Virus del SRAS/inmunología , Síndrome Respiratorio Agudo Grave/complicaciones , Síndrome Respiratorio Agudo Grave/tratamiento farmacológico , Síndrome Respiratorio Agudo Grave/inmunología , Síndrome Respiratorio Agudo Grave/patología
14.
Nat Commun ; 12(1): 216, 2021 01 11.
Artículo en Inglés | MEDLINE | ID: mdl-33431849

RESUMEN

While a number of human coronaviruses are believed to be originated from ancestral viruses in bats, it remains unclear if bat coronaviruses are ready to cause direct bat-to-human transmission. Here, we report the isolation of a MERS-related coronavirus, Tylonycteris-bat-CoV-HKU4, from lesser bamboo bats. Tylonycteris-bat-CoV-HKU4 replicates efficiently in human colorectal adenocarcinoma and hepatocarcinoma cells with cytopathic effects, and can utilize human-dipeptidyl-peptidase-4 and dromedary camel-dipeptidyl-peptidase-4 as the receptors for cell entry. Flow cytometry, co-immunoprecipitation and surface plasmon resonance assays show that Tylonycteris-bat-CoV-HKU4-receptor-binding-domain can bind human-dipeptidyl-peptidase-4, dromedary camel-dipeptidyl-peptidase-4, and Tylonycteris pachypus-dipeptidyl-peptidase-4. Tylonycteris-bat-CoV-HKU4 can infect human-dipeptidyl-peptidase-4-transgenic mice by intranasal inoculation with self-limiting disease. Positive virus and inflammatory changes were detected in lungs and brains of infected mice, associated with suppression of antiviral cytokines and activation of proinflammatory cytokines and chemokines. The results suggest that MERS-related bat coronaviruses may overcome species barrier by utilizing dipeptidyl-peptidase-4 and potentially emerge in humans by direct bat-to-human transmission.


Asunto(s)
Quirópteros/virología , Infecciones por Coronavirus/virología , Dipeptidil Peptidasa 4/metabolismo , Coronavirus del Síndrome Respiratorio de Oriente Medio/aislamiento & purificación , Animales , Encéfalo/patología , Células CACO-2 , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/patología , Infecciones por Coronavirus/transmisión , Citocinas/metabolismo , Dipeptidil Peptidasa 4/genética , Células HEK293 , Especificidad del Huésped , Humanos , Pulmón/patología , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Coronavirus del Síndrome Respiratorio de Oriente Medio/genética
15.
BMC Biol ; 19(1): 12, 2021 01 22.
Artículo en Inglés | MEDLINE | ID: mdl-33482803

RESUMEN

BACKGROUND: Pandemics, even more than other medical problems, require swift integration of knowledge. When caused by a new virus, understanding the underlying biology may help finding solutions. In a setting where there are a large number of loosely related projects and initiatives, we need common ground, also known as a "commons." Wikidata, a public knowledge graph aligned with Wikipedia, is such a commons and uses unique identifiers to link knowledge in other knowledge bases. However, Wikidata may not always have the right schema for the urgent questions. In this paper, we address this problem by showing how a data schema required for the integration can be modeled with entity schemas represented by Shape Expressions. RESULTS: As a telling example, we describe the process of aligning resources on the genomes and proteomes of the SARS-CoV-2 virus and related viruses as well as how Shape Expressions can be defined for Wikidata to model the knowledge, helping others studying the SARS-CoV-2 pandemic. How this model can be used to make data between various resources interoperable is demonstrated by integrating data from NCBI (National Center for Biotechnology Information) Taxonomy, NCBI Genes, UniProt, and WikiPathways. Based on that model, a set of automated applications or bots were written for regular updates of these sources in Wikidata and added to a platform for automatically running these updates. CONCLUSIONS: Although this workflow is developed and applied in the context of the COVID-19 pandemic, to demonstrate its broader applicability it was also applied to other human coronaviruses (MERS, SARS, human coronavirus NL63, human coronavirus 229E, human coronavirus HKU1, human coronavirus OC4).


Asunto(s)
COVID-19/patología , Genómica/métodos , Bases del Conocimiento , Proteómica/métodos , SARS-CoV-2/fisiología , COVID-19/metabolismo , COVID-19/virología , Coronavirus/genética , Coronavirus/fisiología , Infecciones por Coronavirus/metabolismo , Infecciones por Coronavirus/patología , Infecciones por Coronavirus/virología , Genoma Viral , Humanos , Internet , Pandemias , SARS-CoV-2/genética , Proteínas Virales/genética , Proteínas Virales/metabolismo , Flujo de Trabajo
16.
mBio ; 12(1)2021 01 08.
Artículo en Inglés | MEDLINE | ID: mdl-33419872

RESUMEN

In December 2019 a new coronavirus (CoV) emerged as a human pathogen, SARS-CoV-2. There are few data on human coronavirus infections among individuals living with HIV. In this study we probed the role of pneumococcal coinfections with seasonal CoVs among children living with and without HIV hospitalized for pneumonia. We also described the prevalence and clinical manifestations of these infections. A total of 39,836 children who participated in a randomized, double-blind, placebo-controlled clinical trial on the efficacy of a 9-valent pneumococcal conjugate vaccine (PCV9) were followed for lower respiratory tract infection hospitalizations until 2 years of age. Nasopharyngeal aspirates were collected at the time of hospitalization and were screened by PCR for four seasonal CoVs. The frequency of CoV-associated pneumonia was higher in children living with HIV (19.9%) than in those without HIV (7.6%, P < 0.001). Serial CoV infections were detected in children living with HIV. The case fatality risk among children with CoV-associated pneumonia was higher in those living with HIV (30.4%) than without HIV (2.9%, P = 0.001). C-reactive protein and procalcitonin levels were elevated in 36.8% (≥40 mg/liter) and 64.7% (≥0.5 ng/ml), respectively, of the fatal cases living with HIV. Among children without HIV, there was a 64.0% (95% CI: 22.9% to 83.2%) lower incidence of CoV-associated pneumonia hospitalizations among PCV9 recipients compared to placebo recipients. These data suggest that Streptococcus pneumoniae infections might have a role in the development of pneumonia associated with endemic CoVs, that PCV may prevent pediatric CoV-associated hospitalization, and that children living with HIV with CoV infections develop more severe outcomes.IMPORTANCE SARS-CoV-2 may cause severe hospitalization, but little is known about the role of secondary bacterial infection in these severe cases, beyond the observation of high levels of reported inflammatory markers, associated with bacterial infection, such as procalcitonin. We did a secondary analysis of a double-blind randomized trial of PCV to examine its impact on human CoV infections before the pandemic. We found that both children living with and without HIV randomized to receive PCV had evidence of less hospitalization due to seasonal CoV, suggesting that pneumococcal coinfection may play a role in severe hospitalized CoV infections.


Asunto(s)
Infecciones Oportunistas Relacionadas con el SIDA/prevención & control , Infecciones por Coronavirus/prevención & control , Vacunas Neumococicas/administración & dosificación , Neumonía Viral/prevención & control , Streptococcus pneumoniae/inmunología , Infecciones Oportunistas Relacionadas con el SIDA/epidemiología , Infecciones Oportunistas Relacionadas con el SIDA/patología , Coinfección/epidemiología , Coinfección/microbiología , Coinfección/prevención & control , Coinfección/virología , Coronavirus/clasificación , Coronavirus/aislamiento & purificación , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/patología , Estudios de Seguimiento , Hospitalización/estadística & datos numéricos , Humanos , Incidencia , Lactante , Neumonía Neumocócica/epidemiología , Neumonía Neumocócica/prevención & control , Neumonía Viral/epidemiología , Prevalencia , Ensayos Clínicos Controlados Aleatorios como Asunto
17.
Viruses ; 13(1)2021 Jan 17.
Artículo en Inglés | MEDLINE | ID: mdl-33477379

RESUMEN

Porcine deltacoronavirus (PDCoV) strain OH-FD22 infects poultry and shares high nucleotide identity with sparrow-origin deltacoronaviruses (SpDCoV) ISU73347 and HKU17 strains. We hypothesized that the spike (S) protein or receptor-binding domain (RBD) from these SpDCoVs would alter the host and tissue tropism of PDCoV. First, an infectious cDNA clone of PDCoV OH-FD22 strain (icPDCoV) was generated and used to construct chimeric icPDCoVs harboring the S protein of HKU17 (icPDCoV-SHKU17) or the RBD of ISU73347 (icPDCoV-RBDISU). To evaluate their pathogenesis, neonatal gnotobiotic pigs were inoculated orally/oronasally with the recombinant viruses or PDCoV OH-FD22. All pigs inoculated with icPDCoV or OH-FD22 developed severe diarrhea and shed viral RNA at moderate-high levels (7.62-10.56 log10 copies/mL) in feces, and low-moderate levels in nasal swabs (4.92-8.48 log10 copies/mL). No pigs in the icPDCoV-SHKU17 and icPDCoV-RBDISU groups showed clinical signs. Interestingly, low-moderate levels (5.07-7.06 log10 copies/mL) of nasal but not fecal viral RNA shedding were detected transiently at 1-4 days post-inoculation in 40% (2/5) of icPDCoV-SHKU17- and 50% (1/2) of icPDCoV-RBDISU-inoculated pigs. These results confirm that PDCoV infected both the upper respiratory and intestinal tracts of pigs. The chimeric viruses displayed an attenuated phenotype with the loss of tropism for the pig intestine. The SpDCoV S protein and RBD reduced viral replication in pigs, suggesting limited potential for cross-species spillover upon initial passage.


Asunto(s)
Infecciones por Coronavirus/patología , Deltacoronavirus/genética , Intestinos/patología , Sistema Respiratorio/patología , Glicoproteína de la Espiga del Coronavirus/genética , Tropismo Viral/genética , Secuencias de Aminoácidos , Animales , Enfermedades de las Aves/virología , Línea Celular , Deltacoronavirus/patogenicidad , Intestinos/virología , Proteínas Recombinantes/genética , Sistema Respiratorio/virología , Gorriones , Porcinos , Enfermedades de los Porcinos/virología , Virulencia/genética
18.
BMC Bioinformatics ; 22(1): 18, 2021 Jan 07.
Artículo en Inglés | MEDLINE | ID: mdl-33413085

RESUMEN

BACKGROUND: The ongoing global COVID-19 pandemic is caused by SARS-CoV-2, a novel coronavirus first discovered at the end of 2019. It has led to more than 50 million confirmed cases and more than 1 million deaths across 219 countries as of 11 November 2020, according to WHO statistics. SARS-CoV-2, SARS-CoV, and MERS-CoV are similar. They are highly pathogenic and threaten public health, impair the economy, and inflict long-term impacts on society. No drug or vaccine has been approved as a treatment for these viruses. Efforts to develop antiviral measures have been hampered by the insufficient understanding of how the human body responds to viral infections at the cellular and molecular levels. RESULTS: In this study, journal articles and transcriptomic and proteomic data surveying coronavirus infections were collected. Response genes and proteins were then identified by differential analyses comparing gene/protein levels between infected and control samples. Finally, the H2V database was created to contain the human genes and proteins that respond to SARS-CoV-2, SARS-CoV, and MERS-CoV infection. CONCLUSIONS: H2V provides molecular information about the human response to infection. It can be a powerful tool to discover cellular pathways and processes relevant for viral pathogenesis to identify potential drug targets. It is expected to accelerate the process of antiviral agent development and to inform preparations for potential future coronavirus-related emergencies. The database is available at: http://www.zhounan.org/h2v .


Asunto(s)
COVID-19/metabolismo , Infecciones por Coronavirus/metabolismo , Bases de Datos Genéticas , Bases de Datos de Proteínas , Síndrome Respiratorio Agudo Grave/metabolismo , Interfaz Usuario-Computador , COVID-19/genética , COVID-19/patología , COVID-19/virología , Infecciones por Coronavirus/genética , Infecciones por Coronavirus/patología , Infecciones por Coronavirus/virología , Humanos , Coronavirus del Síndrome Respiratorio de Oriente Medio/fisiología , Proteómica , Virus del SRAS/fisiología , SARS-CoV-2/fisiología , Síndrome Respiratorio Agudo Grave/genética , Síndrome Respiratorio Agudo Grave/patología , Síndrome Respiratorio Agudo Grave/virología
19.
J Infect Chemother ; 27(1): 70-75, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32950393

RESUMEN

OBJECTIVES: The symptoms of Coronavirus disease 2019 (COVID-19) vary among patients. The aim of this study was to investigate the clinical manifestation and disease duration in young versus elderly patients. METHODS: We retrospectively analyzed 187 patients (87 elderly and 100 young patients) with confirmed COVID-19. The clinical characteristics and chest computed tomography (CT) extent as defined by a score were compared between the two groups. RESULTS: The numbers of asymptomatic cases and severe cases were significantly higher in the elderly group (elderly group vs. young group; asymptomatic cases, 31 [35.6%] vs. 10 [10%], p < 0.0001; severe cases, 25 [28.7%] vs. 8 [8.0%], p = 0.0002). The proportion of asymptomatic patients and severe patients increased across the 10-year age groups. There was no significant difference in the total CT score and number of abnormal cases. A significant positive correlation between the disease duration and patient age was observed in asymptomatic patients (ρ = 0.4570, 95% CI 0.1198-0.6491, p = 0.0034). CONCLUSIONS: Although the extent of lung involvement did not have a significant difference between the young and elderly patients, elderly patients were more likely to have severe clinical manifestations. Elderly patients were also more likely to be asymptomatic and a source of COVID-19 viral shedding.


Asunto(s)
Infecciones Asintomáticas/epidemiología , Infecciones por Coronavirus/epidemiología , Neumonía Viral/epidemiología , Esparcimiento de Virus , Adulto , Factores de Edad , Anciano , Betacoronavirus , COVID-19 , Infecciones por Coronavirus/diagnóstico por imagen , Infecciones por Coronavirus/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/diagnóstico por imagen , Neumonía Viral/patología , Estudios Retrospectivos , SARS-CoV-2 , Índice de Severidad de la Enfermedad , Tomografía Computarizada por Rayos X
20.
Virology ; 552: 43-51, 2021 01 02.
Artículo en Inglés | MEDLINE | ID: mdl-33059319

RESUMEN

This study focused on intestinal restitution including phenotype switching of absorptive enterocytes and the abundance of different enterocyte subtypes in weaned pigs after porcine epidemic diarrhea virus (PEDV) infection. At 10 days post-PEDV-inoculation, the ratio of villus height to crypt depth in both jejunum and ileum had restored, and the PEDV antigen was not detectable. However, enterocytes at the villus tips revealed epithelial-mesenchymal transition (EMT) in the jejunum in which E-cadherin expression decreased while expression of N-cadherin, vimentin, and Snail increased. Additionally, there was reduced expression of actin in microvilli and Zonula occludens-1 (ZO-1) in tight junctions. Moreover, the protein concentration of transforming growth factor ß1 (TGFß1), which mediates EMT and cytoskeleton alteration, was increased. We also found a decreased number of Peyer's patch M cells in the ileum. These results reveal incomplete restitution of enterocytes in the jejunum and potentially impaired immune surveillance in the ileum after PEDV infection.


Asunto(s)
Infecciones por Coronavirus/veterinaria , Enterocitos/patología , Transición Epitelial-Mesenquimal , Gastroenteritis Porcina Transmisible/patología , Ganglios Linfáticos Agregados/patología , Virus de la Diarrea Epidémica Porcina/patogenicidad , Animales , Cadherinas/metabolismo , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/patología , Infecciones por Coronavirus/virología , Gastroenteritis Porcina Transmisible/inmunología , Gastroenteritis Porcina Transmisible/virología , Íleon/inmunología , Íleon/patología , Mucosa Intestinal/patología , Yeyuno/inmunología , Yeyuno/patología , Microvellosidades/patología , Porcinos , Uniones Estrechas/patología , Factor de Crecimiento Transformador beta1/metabolismo , Destete
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