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Radial glial cells (RGCs) as primary neural stem cells in the developing mammalian cortex give rise to diverse types of neurons and glial cells according to sophisticated developmental programs with remarkable spatiotemporal precision. Recent studies suggest that regulation of the temporal competence of RGCs is a key mechanism for the highly conserved and predictable development of the cerebral cortex. Various types of epigenetic regulations, such as DNA methylation, histone modifications, and 3D chromatin architecture, play a key role in shaping the gene expression pattern of RGCs. In addition, epitranscriptomic modifications regulate temporal pre-patterning of RGCs by affecting the turnover rate and function of cell-type-specific transcripts. In this review, we summarize epigenetic and epitranscriptomic regulatory mechanisms that control the temporal competence of RGCs during mammalian corticogenesis. Furthermore, we discuss various developmental elements that also dynamically regulate the temporal competence of RGCs, including biochemical reaction speed, local environmental changes, and subcellular organelle remodeling. Finally, we discuss the underlying mechanisms that regulate the interspecies developmental tempo contributing to human-specific features of brain development.
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Células-Madre Neurales , Neurogénesis , Animales , Humanos , Neurogénesis/fisiología , Células-Madre Neurales/metabolismo , Neuronas/metabolismo , Neuroglía/metabolismo , Corteza Cerebral , MamíferosRESUMEN
Acute gastric dilatation (AGD) is one of the most prevalent and life-threatening diseases in nonhuman primates worldwide. However, the etiology of this syndrome has not been determined. Recently, sudden death occurred in a 7-year-old female cynomolgus monkey with a history of fecal microbiota transplantation using diarrheic stools. The monkey had undergone surgery previously. On necropsy, gastric dilatation and rupture demonstrated a tetrad arrangement on histopathologic examination. On 16S rRNA sequencing, a high population of Clostridium ventriculi was identified in the duodenum adjacent to stomach but not in the colon. This paper is the first report of Clostridium ventriculi infection in a cynomolgus macaque with acute gastric dilatation and rupture.
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Clostridium , Dilatación Gástrica , Femenino , Animales , Macaca fascicularis , Dilatación Gástrica/veterinaria , Dilatación Gástrica/patología , ARN Ribosómico 16SRESUMEN
Recently emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variants are generally less pathogenic than previous strains. However, elucidating the molecular basis for pulmonary immune response alterations is challenging owing to the virus's heterogeneous distribution within complex tissue structure. Here, we revealed the spatial transcriptomic profiles of pulmonary microstructures at the SARS-CoV-2 infection site in the nine cynomolgus macaques upon inoculation with the Delta and Omicron variants. Delta- and Omicron-infected lungs had upregulation of genes involved in inflammation, cytokine response, complement, cell damage, proliferation, and differentiation pathways. Depending on the tissue microstructures (alveoli, bronchioles, and blood vessels), there were differences in the types of significantly upregulated genes in each pathway. Notably, a limited number of genes involved in cytokine and cell damage response were differentially expressed between bronchioles of the Delta- and Omicron-infection groups. These results indicated that despite a significant antigenic shift in SARS-CoV-2, the host immune response mechanisms induced by the variants were relatively consistent, with limited transcriptional alterations observed only in large airways. This study may aid in understanding the pathogenesis of SARS-CoV-2 and developing a clinical strategy for addressing immune dysregulation by identifying potential transcriptional biomarkers within pulmonary microstructures during infection with emerging variants.
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COVID-19 , SARS-CoV-2 , Animales , SARS-CoV-2/genética , Transcriptoma , COVID-19/genética , Alveolos Pulmonares , Citocinas/genética , MacacaRESUMEN
Germinal centers (GCs) elicit protective humoral immunity through a combination of antibody-secreting cells and memory B cells, following pathogen invasion or vaccination. However, the possibility of a GC response inducing protective immunity against reinfection following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remains unknown. We found GC activity was consistent with seroconversion observed in recovered macaques and humans. Rechallenge with a different clade of virus resulted in significant reduction in replicating virus titers in respiratory tracts in macaques with high GC activity. However, diffuse alveolar damage and increased fibrotic tissue were observed in lungs of reinfected macaques. Our study highlights the importance of GCs developed during natural SARS-CoV-2 infection in managing viral loads in subsequent infections. However, their ability to alleviate lung damage remains to be determined. These results may improve understanding of SARS-CoV-2-induced immune responses, resulting in better coronavirus disease 2019 (COVID-19) diagnosis, treatment, and vaccine development.
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COVID-19 , Centro Germinal , Inmunidad Humoral , Reinfección/inmunología , Animales , Anticuerpos Antivirales , COVID-19/inmunología , Humanos , Pulmón/patología , Pulmón/virología , Macaca , Células B de Memoria , SeroconversiónRESUMEN
Dengue virus (DV) is a mosquito-borne virus that is endemic to many tropical and subtropical areas. Recently, the annual incidence of DV infection has increased worldwide, including in Korea, due to global warming and increased global travel. We therefore sought to characterize the molecular and evolutionary features of DV-1 and DV-4 isolated from Korean overseas travelers. We used phylogenetic analysis based on the full coding region to classify isolates of DV-1 in Korea into genotype I (43251, KP406802), genotype IV (KP406803), and genotype V (KP406801). In addition, we found that strains of DV-4 belonged to genotype I (KP406806) and genotype II (43257). Evidence of positive selection in DV-1 strains was identified in the C, prM, NS2A, and NS5 proteins, whereas DV-4 showed positive selection only in the non-structural proteins NS2A, NS3, and NS5. The substitution rates per site per year were 5.58 × 10-4 and 6.72 × 10-4 for DV-1 and DV-4, respectively, and the time of the most recent common ancestor was determined using the Bayesian skyline coalescent method. In this study, the molecular, phylogenetic, and evolutionary characteristics of Korean DV-1 and DV-4 isolates were evaluated for the first time.
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Virus del Dengue/genética , Dengue/virología , Evolución Molecular , Viaje , Secuencia de Aminoácidos , Sustitución de Aminoácidos , Secuencia de Bases , Dengue/epidemiología , Virus del Dengue/clasificación , Virus del Dengue/aislamiento & purificación , Genotipo , Humanos , Filogenia , ARN Viral/genética , República de Corea/epidemiología , Selección Genética , Serogrupo , Proteínas Virales/genéticaRESUMEN
Using a reliable primate model is critical for developing therapeutic advances to treat humans infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Here, we exposed macaques to high titers of SARS-CoV-2 via combined transmission routes. We observed acute interstitial pneumonia with endotheliitis in the lungs of all infected macaques. All macaques had a significant loss of total lymphocytes during infection, which were restored over time. These data show that SARS-CoV-2 causes a coronavirus disease 2019 (COVID-19)-like disease in macaques. This new model could investigate the interaction between SARS-CoV-2 and the immune system to test therapeutic strategies.
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Betacoronavirus/genética , Infecciones por Coronavirus/complicaciones , Modelos Animales de Enfermedad , Enfermedades Pulmonares Intersticiales/complicaciones , Linfopenia/complicaciones , Enfermedades de los Monos/virología , Neumonía Viral/complicaciones , Animales , COVID-19 , Infecciones por Coronavirus/patología , Infecciones por Coronavirus/virología , Femenino , Enfermedades Pulmonares Intersticiales/patología , Linfopenia/patología , Macaca fascicularis , Macaca mulatta , Masculino , Enfermedades de los Monos/patología , Pandemias , Neumonía Viral/patología , Neumonía Viral/virología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , SARS-CoV-2RESUMEN
Chronic inflammatory enteric diseases occur commonly in humans and animals, especially in captive bred macaques. However, information about the etiology of idiopathic chronic inflammatory diarrhea in cynomolgus monkeys is limited. In this paper, we reported the unusual case of idiopathic chronic diarrhea in a captive cynomolgus monkey based on microbial, imaging, and microbiome examinations.
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Diarrea/veterinaria , Disbiosis/veterinaria , Macaca fascicularis , Enfermedades de los Monos/etiología , Animales , Enfermedad Crónica/veterinaria , Diarrea/complicaciones , Diarrea/etiología , Diarrea/inmunología , Disbiosis/complicaciones , Disbiosis/etiología , Disbiosis/inmunología , Femenino , Enfermedades de los Monos/inmunologíaRESUMEN
In Korea, dengue infection has been frequently reported in travelers to tropical and subtropical countries. Global warming increases the probability of autochthonous dengue outbreaks in Korea. In this report, the molecular and evolutionary properties of four dengue virus (DENV) type 2 isolates from Korean overseas travelers were examined. Three of these isolates were classified as Cosmopolitan genotypes and further divided into sublineages 1 (43,253, 43,254) and 2 (43,248), while the other isolate (KBPV-VR29) was related to American genotypes. The variable amino acid motifs related to virulence and replication were identified in the structural and non-structural proteins. A negative selection mechanism was clearly verified in all of the DENV proteins. Potential recombination events were identified in the NS5 protein of the XSBN10 strain. The substitution rate (5.32 × 10-4 substitutions per site) and the time of the most recent common ancestor (TMRCA) for each evolutionary group were determined by the Bayesian skyline coalescent method. This study shows that DENV type 2 strains with distinct phylogenetic, evolutionary, and virulence characteristics have been introduced into Korea by overseas travelers and have the potential to trigger autochthonous dengue outbreaks.
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Virus del Dengue/genética , Virus del Dengue/aislamiento & purificación , Sustitución de Aminoácidos/genética , Dengue/virología , Brotes de Enfermedades , Evolución Molecular , Genoma Viral/genética , Genotipo , Humanos , Filogenia , ARN Viral/genética , República de Corea , Serogrupo , Proteínas Virales/genética , Virulencia/genética , Replicación Viral/genéticaRESUMEN
Clostridium perfringens is ubiquitous in the environment and the gastrointestinal tract of warm-blooded animals. While part of the gut microbiome, abnormal growth of C. perfringens causes histotoxic, neurologic, and enteric diseases in a variety of animal species, including humans, due to the production of toxins. There is extremely limited information on C. perfringens infection in non-human primates. Presently, 10 strains were successfully isolated from 126 monkeys and confirmed by molecular and biochemical analyses. All isolates were genotype A based on molecular analysis. Alpha toxin was identified in all isolates. Beta 2 toxin was detected in only three isolates. No other toxins, including enterotoxin, beta, iota, epsilon, and net B toxin, were identified in any isolate. All isolates were highly susceptible to ß-lactam antibiotics. Double hemolysis and lecithinase activity were commonly observed in all strains. Biofilm formation, which can increase antibiotic resistance, was identified in 90% of the isolates. The data are the first report the prevalence and characteristics of C. perfringens isolated from captive cynomolgus monkeys.
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Toxinas Bacterianas/genética , Biopelículas/crecimiento & desarrollo , Clostridium perfringens/efectos de los fármacos , Clostridium perfringens/genética , Farmacorresistencia Bacteriana Múltiple , Macaca fascicularis/microbiología , Animales , Antibacterianos/farmacología , Proteínas Bacterianas/genética , Infecciones por Clostridium/microbiología , Infecciones por Clostridium/veterinaria , Clostridium perfringens/aislamiento & purificación , ADN Bacteriano/genética , Heces/microbiología , Femenino , Genotipo , Masculino , Filogenia , Prevalencia , ARN Ribosómico 16S/genética , beta-Lactamas/farmacologíaRESUMEN
In recent decades, many studies on the treatment and prevention of pancreatic cancer have been conducted. However, pancreatic cancer remains incurable, with a high mortality rate. Although mouse models have been widely used for preclinical pancreatic cancer research, these models have many differences from humans. Therefore, large animals may be more useful for the investigation of pancreatic cancer. Pigs have recently emerged as a new model of pancreatic cancer due to their similarities to humans, but no pig pancreatic cancer cell lines have been established for use in drug screening or analysis of tumor biology. Here, we established and characterized an immortalized miniature pig pancreatic cell line derived from primary pancreatic cells and pancreatic cancer-like cells expressing K-rasG12D regulated by the human PTF1A promoter. Using this immortalized cell line, we analyzed the gene expression and phenotypes associated with cancer cell characteristics. Notably, we found that acinar-to-ductal transition was caused by K-rasG12D in the cell line constructed from acinar cells. This may constitute a good research model for the analysis of acinar-to-ductal metaplasia in human pancreatic cancer.
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Páncreas/metabolismo , Neoplasias Pancreáticas/genética , Lesiones Precancerosas/genética , Proteínas Proto-Oncogénicas p21(ras)/genética , Animales , Línea Celular , Transformación Celular Neoplásica/genética , Modelos Animales de Enfermedad , Regulación Neoplásica de la Expresión Génica/genética , Páncreas/patología , Conductos Pancreáticos/metabolismo , Conductos Pancreáticos/patología , Neoplasias Pancreáticas/patología , Lesiones Precancerosas/metabolismo , Lesiones Precancerosas/patología , Transducción de Señal/genética , Porcinos , Porcinos EnanosRESUMEN
Gene segments from avian H1N1 influenza A viruses have reassorted with other influenza viruses to generate pandemic strains over the past century. Nevertheless, little effort has been invested in understanding the characteristics of avian H1N1 influenza viruses. Here, we present the genome sequence and a molecular and virological characterization of an avian influenza A virus, A/wild bird/Korea/SK14/2014 (A/SK14, H1N1), isolated from migratory birds in South Korea during the winter season of 2014-2015. Full-genome sequencing and phylogenetic analysis revealed that the virus belongs to the Eurasian avian lineage. Although it retained avian-receptor binding preference, A/SK14 virus also exhibited detectable human-like receptor binding and was able to replicate in differentiated primary normal human bronchial epithelial cells. In animal models, A/SK14 virus was moderately pathogenic in mice, and virus was detected in nasal washes from inoculated guinea pigs, but not in direct-contact guinea pigs. Although A/SK14 showed moderate pathogenicity and no evidence of transmission in a mammalian model, our results suggest that the dual receptor specificity of A/SK14-like virus might allow for a more rapid adaptation to mammals, emphasizing the importance of further continuous surveillance and risk-assessment activities.
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Genoma Viral , Subtipo H1N1 del Virus de la Influenza A/genética , Subtipo H1N1 del Virus de la Influenza A/patogenicidad , Gripe Aviar/virología , Infecciones por Orthomyxoviridae/veterinaria , Animales , Animales Salvajes , Aves/virología , Bronquios/citología , Bronquios/virología , Células Cultivadas , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Subtipo H1N1 del Virus de la Influenza A/clasificación , Subtipo H1N1 del Virus de la Influenza A/fisiología , Infecciones por Orthomyxoviridae/virología , Filogenia , Virus Reordenados/patogenicidad , Receptores Virales/metabolismo , República de Corea , Acoplamiento Viral , Replicación ViralRESUMEN
Chicken parvovirus (ChPV) is one of the causative agents of viral enteritis. Recently, the genome of the ABU-P1 strain of ChPV was fully sequenced and determined to have a distinct genomic composition compared with that of vertebrate parvoviruses. However, no comparative sequence analysis of coding regions of ChPVs was possible because of the lack of other sequence information. In this study, we obtained the nucleotide sequences of all genomic coding regions of three ChPVs by polymerase chain reaction using 13 primer sets, and deduced the amino acid sequences from the nucleotide sequences. The non-structural protein 1 (NS1) gene of the three ChPVs showed 95.0 to 95.5% nucleotide sequence identity and 96.5 to 98.1% amino acid sequence identity to those of NS1 from the ABU-P1 strain, respectively, and even higher nucleotide and amino acid similarities to one another. The viral proteins (VP) gene was more divergent between the three ChPV Korean strains and ABU-P1, with 88.1 to 88.3% nucleotide identity and 93.0% amino acid identity. Analysis of the putative tertiary structure of the ChPV VP2 protein showed that variable regions with less than 80% nucleotide similarity between the three Korean strains and ABU-P1 occurred in large loops of the VP2 protein believed to be involved in antigenicity, pathogenicity, and tissue tropism in other parvoviruses. Based on our analysis of full-length coding sequences, we discovered greater variation in ChPV strains than reported previously, especially in partial regions of the VP2 protein.
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Pollos/virología , Variación Genética , Parvovirus/genética , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Cartilla de ADN/genética , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa/veterinaria , Análisis de Secuencia de ADN/veterinaria , Homología de Secuencia , Especificidad de la EspecieRESUMEN
Outbreaks of highly pathogenic avian influenza (HPAI) virus, subtype H5N8, were observed in two different flocks of local broiler breeder farms and a commercial layer farm in South Korea. Clinically, the cases were characterized by a gradual increase in mortality, slow transmission, and unrecognizable clinical signs of HPAI. Gross observations in both cases included hemorrhagic or necrotic lesions in internal organs, such as serosal and mucosal membranes, spleen, and pancreas. Both cases exhibited similar histopathologic lesions, including multifocal malacia in the brain and multifocal or diffuse necrosis in the spleen and pancreas. Immunohistochemical results indicated that neurons and glial cells in the brain, myocytes in the heart, acinar cells in the pancreas, and mononuclear phagocytic cells in several visceral organs were immunopositive for avian influenza viral antigen. To experimentally reproduce the low pathogenicity and the mortality observed in these two cases, 18 specific-pathogen-free chickens and 18 commercial layers were divided into an H5N8 virus-inoculated group and a contact-exposed group. The mortality of the chickens in the inoculation group was 50%-100%, whereas the mean time to death was delayed or death did not occur in the contact-exposed group. The distributions of the viral antigens and histopathologic lesions in the experimental study were similar to those observed in the field cases. These findings suggest that the H5N8 virus induces a different pattern of pathobiology, including slow transmission and low mortality, compared with that of other HPAI viruses. This is the first pathologic description of natural cases of H5N8 in South Korea, and it may be helpful in understanding the pathobiology of novel H5N8 HPAI viruses.
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Virus de la Influenza A/patogenicidad , Gripe Aviar/virología , Animales , Pollos , Femenino , Gripe Aviar/epidemiología , Gripe Aviar/patología , República de Corea/epidemiología , VirulenciaRESUMEN
After the first outbreak, SARS-CoV-2 infection continues to occur due to the emergence of new variants. There is limited information available on the comparative evaluation of evolutionary characteristics of SARS-CoV-2 among different countries over time, and its relatedness to epidemiological and socio-environmental factors within those countries. We assessed comparative Bayesian evolutionary characteristics for SARS-CoV-2 in eight countries from 2020 to 2022 using BEAST version 2.6.7. Additionally, the relatedness between virus evolution factors and both epidemiological and socio-environmental factors was analyzed using Pearson's correlation coefficient. The estimated substitution rates in the gene encoding S protein of SARS-CoV-2 exhibited a continuous increase from 2020 to 2022 and were divided into two distinct groups in 2022 (p value < 0.05). Effective population size (Ne) generally showed decreased patterns by time. Notably, the change rates of the substitution rates were negatively correlated with the cumulative vaccination rates in 2021. A strict and rapid vaccination policy in the United Arab Emirates dramatically reduced the evolution of the virus, compared to other countries. Also, the average yearly temperature in countries were negatively correlated with the substitution rates. The changes of six epitopes in SARS-CoV-2 were related to various socio-environmental factors. We figured out comparative virus evolutionary traits and the association of epidemiological and socio-environmental factors especially cumulative vaccination rates and average temperature.
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Infectious bronchitis virus (IBV) replicates primarily in the respiratory tract and grows in various organs in chickens, with or without pathological effects. The diversity of this virus has been verified by sequence analysis of the S1 glycoprotein gene, but this method must be supplemented with further analysis for characterization of the agent. To increase our understanding of the pathogenesis of the disease caused by this virus, we investigated the response of chickens to 2 IBV with different genotypes, KIIa and ChVI. The clinical signs induced by the viruses were observed. In addition, the mRNA levels of the pro-inflammatory cytokines, IL-6, IL-1ß, and lipopolysaccharide-induced tumor necrosis factor-α factor and the serum levels of α1-acid glycoprotein, which is a major acute phase protein, were measured. The KIIa genotype (Kr/ADL110002/2011) induced clinical signs accompanied by the excessive production of pro-inflammatory cytokines and a higher viral load. In chickens infected with this isolate, simultaneous peaks in the viral copy number and cytokine production were observed at 7 dpi in the trachea and 9 d postinoculation in the kidney. On the other hand, the chickens infected with the ChVI genotype (Kr/ADL120003/2012) did not show a response other than a mild upregulation of cytokines at 1 d postinoculation, which appears to indicate the invasion of the virus. In summary, we confirmed a differential innate response following infection with distinct IBV. We hypothesize that an excessive innate response contributes to the scale of the pathophysiologic effect in chickens.
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Pollos , Infecciones por Coronavirus/veterinaria , Citocinas/genética , Inmunidad Innata , Virus de la Bronquitis Infecciosa/patogenicidad , Enfermedades de las Aves de Corral/inmunología , Animales , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/prevención & control , Citocinas/metabolismo , ADN Complementario/análisis , Ensayo de Inmunoadsorción Enzimática/veterinaria , Virus de la Bronquitis Infecciosa/genética , Interleucina-1alfa/genética , Interleucina-1alfa/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Riñón/virología , Orosomucoide/genética , Orosomucoide/metabolismo , Reacción en Cadena de la Polimerasa/veterinaria , Enfermedades de las Aves de Corral/prevención & control , ARN Mensajero/análisis , Análisis de Secuencia de ADN/veterinaria , Tráquea/virología , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo , VirulenciaRESUMEN
Characterizing the host response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at the molecular level is necessary to understand viral pathogenesis and identify clinically relevant biomarkers. However, in humans, the pulmonary host response during disease onset remains poorly understood. Herein, we utilized a spatial transcriptome atlas to identify pulmonary microstructure-specific COVID-19 gene signatures during the acute phase of lung infection in cynomolgus macaques. The innate immune response to virus-induced cell death was primarily active in the alveolar regions involving activated macrophage infiltration. Inflamed vascular regions exhibited prominent upregulation of interferon and complement pathway genes that mediate antiviral activity and tissue damage response. Furthermore, known biomarker genes were significantly expressed in specific microstructures, and some of them were universally expressed across all microstructures. These findings underscore the importance of identifying key drivers of disease progression and clinically applicable biomarkers by focusing on pulmonary microstructures appearing during SARS-CoV-2 infection.
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Ascomicetos , COVID-19 , Humanos , Animales , COVID-19/genética , SARS-CoV-2 , Transcriptoma , Macaca fascicularis , PulmónRESUMEN
Increasing evidence reinforces the essential function of RNA modifications in development and diseases, especially in the nervous system. RNA modifications impact various processes in the brain, including neurodevelopment, neurogenesis, neuroplasticity, learning and memory, neural regeneration, neurodegeneration, and brain tumorigenesis, leading to the emergence of a new field termed neuroepitranscriptomics. Deficiency in machineries modulating RNA modifications has been implicated in a range of brain disorders from microcephaly, intellectual disability, seizures, and psychiatric disorders to brain cancers such as glioblastoma. The inaugural NSAS Challenge Workshop on Brain Epitranscriptomics hosted in Crans-Montana, Switzerland in 2023 assembled a group of experts from the field, to discuss the current state of the field and provide novel translational perspectives. A summary of the discussions at the workshop is presented here to simulate broader engagement from the general neuroscience field.
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Since the outbreak of coronavirus disease (COVID-19) in 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved into diverse variants. Here, an early isolate of SARS-CoV-2 was serially passaged in multiple cell lines of human origin in triplicate, and selected mutations were compared to those found in natural SARS-CoV-2 variants. In the spike protein, Q493R and Q498R substitutions from passaged viruses were consistent with those in the B.1.1.529 (Omicron) variant. Y144del and H655Y substitutions from passaged viruses were also reported in B.1.1.7 (Alpha), P.1 (Gamma), and B.1.1.529 (Omicron) variants. Several single nucleotide polymorphisms (SNPs) found in first-passaged viruses have also been identified as selected mutation sites in serially passaged viruses. Considering the consistent mutations found between serially passaged SARS-CoV-2 and natural variants, there may be host-specific selective mutation patterns of viral evolution in humans. Additional studies on the selective mutations in SARS-CoV-2 experiencing diverse host environments will help elucidate the direction of SARS-CoV-2 evolution. Importance: SARS-CoV-2 isolate (SARS-CoV-2/human/KOR/KCDC03-NCCP43326/2020) was serially passaged in A549, CaCO2, and HRT-18 cells in triplicate. After 12 times of serial passages in each cell lines, several consistent selected mutations were found on spike protein between the serially passaged SARS-CoV-2 in human cell lines and recent natural variants of SARS-CoV-2 like omicron. On the non-spike protein genes, selected mutations were more frequent in viruses passaged in Caco-2 and HRT-18 cells (Colon epithelial-like) than in those passaged in A549 cells (Lung epithelial-like). In addition, several SNPs identified after one round of passaging were consistently identified as the selected mutation sites in serially passaged viruses. Thus, mutation patterns of SARS-CoV-2 in certain host environments may provide researchers information to understand and predict future SARS-CoV-2 variants.
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Dengue viruses (DENVs) exploit monocytes and macrophages for tropism and replication, therefore, establishing a long-term reservoir. However, their roles in dengue pathogenesis remains unclear. Here, using the human monocytic cell line THP-1, human primary monocytes, and non-human primate models, we show that DENV-infected monocytes represent suitable carriers for circulatory viral dissemination. Monocyte-derived macrophages expressing M2 surface markers at the gene level efficiently replicated, while the productivity of monocyte replication was low. However, attachment of DENVs to the cellular surface of monocytes was similar to that of macrophages. Furthermore, after differentiation with type-2 cytokines, DENV-attached monocytes could replicate DENVs. Productive DENV infection was confirmed by intravenous injection of DENVs into nonhuman primate model, in which, DENV attachment to monocytes was positively correlated with viremia. These results provide insight into the role of circulating monocytes in DENV infection, suggesting that monocytes directly assist in DENV dissemination and replication during viremia and could be applied to design antiviral intervention.