RESUMEN

The global challenge of water resource availability is exacerbated by anthropogenic influences that promote the emergence of pollutants. Among these pollutants are microbiological agents, including viruses, which are ubiquitous in the biosphere and play a pivotal role in both ecological balance and the occurrence of diseases in animals and plants. Consequently, monitoring viruses in water sources becomes indispensable for the establishment of effective prevention, promotion, and control strategies. Within this context, the study focuses on the identification of novel viruses belonging to the Picornavirales order in freshwater from the Guarapiranga Reservoir in the state of São Paulo, Brazil. The samples were subjected to viral metagenomics. Our analysis led to the characterization of four distinct sequences (GinkV-05, AquaV_10, MarV_14, and MarV_64), which exhibited significant divergence compared to other members of the Picornavirales order. This remarkable diversity prompted the identification of a potential new genus within the Marnaviridae family, tentatively named Ginkgonavirus. Additionally, we characterized four sequences in a very distinct clade and propose the recognition of a novel family (named Aquaviridae) within the Picornavirales order. Our findings contribute valuable insights into the previously uncharted diversity of Picornavirales present in water sources, shedding light on an important facet of viral ecology and evolution in aquatic environments.

RESUMEN

Epstein-Barr virus (EBV) is a highly successful pathogen that infects ~95% of the adult population and is associated with diverse cancers and autoimmune diseases. The most abundant viral factor in latently infected cells is not a protein but a noncoding RNA called EBV-encoded RNA 1 (EBER1). Even though EBER1 is highly abundant and was discovered over forty years ago, the function of EBER1 has remained elusive. EBER1 interacts with the ribosomal protein L22, which normally suppresses the expression of its paralog L22-like 1 (L22L1). Here we show that when L22 binds EBER1, it cannot suppress L22L1, resulting in L22L1 being expressed and incorporated into ribosomes. We further show that L22L1-containing ribosomes preferentially translate mRNAs involved in the oxidative phosphorylation pathway. Moreover, upregulation of L22L1 is indispensable for growth transformation and immortalization of resting B cells upon EBV infection. Taken together, our results suggest that the function of EBER1 is to modulate host gene expression at the translational level, thus bypassing the need for dysregulating host gene transcription.

Asunto(s)

Herpesvirus Humano 4 , Fosforilación Oxidativa , ARN Viral , Proteínas Ribosómicas , Proteínas Ribosómicas/genética , Proteínas Ribosómicas/metabolismo , Humanos , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/fisiología , ARN Viral/genética , ARN Viral/metabolismo , Linfocitos B/virología , Interacciones Huésped-Patógeno/genética , Infecciones por Virus de Epstein-Barr/virología , Infecciones por Virus de Epstein-Barr/genética , Infecciones por Virus de Epstein-Barr/metabolismo , Ribosomas/metabolismo , Ribosomas/genética , Proteínas de Unión al ARN

RESUMEN

COVID 19 pandemic is still ongoing, having taken more than 6 million human lives with it, and it seems that the world will have to learn how to live with the virus around. In consequence, there is a need to develop different treatments against it, not only with vaccines, but also new medicines. To do this, human-virus protein-protein interactions (PPIs) play a key part in drug-target discovery, but finding them experimentally can be either costly or sometimes unreliable. Therefore, computational methods arose as a powerful alternative to predict these interactions, reducing costs and helping researchers confirm only certain interactions instead of trying all possible combinations in the laboratory. Malivhu is a tool that predicts human-virus PPIs through a 4-phase process using machine learning models, where phase 1 filters ssRNA(+) class virus proteins, phase 2 filters Coronaviridae family proteins and phase 3 filters severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) species proteins, and phase 4 predicts human-SARS-CoV/SARS-CoV-2/MERS protein-protein interactions. The performance of the models was measured with Matthews correlation coefficient, F1-score, specificity, sensitivity, and accuracy scores, getting accuracies of 99.07%, 99.83%, and 100% for the first 3 phases, respectively, and 94.24% for human-SARS-CoV PPI, 94.50% for human-SARS-CoV-2 PPI, and 95.45% for human-MERS PPI on independent testing. All the prediction models developed for each of the 4 phases were implemented as web server which is freely available at https://kaabil.net/malivhu/.

RESUMEN

Extracellular vesicles (EVs) are shown to be a novel viral transmission model capable of increasing a virus's tropism. According to our earlier research, cells infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or transfected with envelope protein plasmids generate a novel type of EVs that are micrometer-sized and able to encase virus particles. Here, we showed the capacity of these EVs to invade various animals both in vitro and in vivo independent of the angiotensin-converting enzyme 2 receptor. First, via macropinocytosis, intact EVs produced from Vero E6 (monkey) cells were able to enter cells from a variety of animals, including cats, dogs, bats, hamsters, and minks, and vice versa. Second, when given to zebrafish with cutaneous wounds, the EVs showed favorable stability in aqueous environments and entered the fish. Moreover, infection of wild-type (WT) mice with heterogeneous EVs carrying SARS-CoV-2 particles led to a strong cytokine response and a notable amount of lung damage. Conversely, free viral particles did not infect WT mice. These results highlight the variety of processes behind viral transmission and cross-species evolution by indicating that EVs may be possible vehicles for SARS-CoV-2 spillover and raising risk concerns over EVs' potential for viral gene transfer.

Asunto(s)

COVID-19 , Vesículas Extracelulares , SARS-CoV-2 , Animales , Vesículas Extracelulares/virología , Vesículas Extracelulares/metabolismo , SARS-CoV-2/fisiología , SARS-CoV-2/patogenicidad , SARS-CoV-2/genética , COVID-19/transmisión , COVID-19/virología , Ratones , Chlorocebus aethiops , Células Vero , Humanos , Cricetinae , Proteínas de la Envoltura de Coronavirus/metabolismo , Proteínas de la Envoltura de Coronavirus/genética , Perros , Pez Cebra/virología , Gatos , Quirópteros/virología , Enzima Convertidora de Angiotensina 2/metabolismo , Enzima Convertidora de Angiotensina 2/genética

RESUMEN

Fungi harbor a vast diversity of mobile genetic elements (MGEs). Recently, novel fungal MGEs, tentatively referred to as 'ambiviruses,' were described. 'Ambiviruses' have single-stranded RNA genomes of about 4-5 kb in length that contain at least two open reading frames (ORFs) in non-overlapping ambisense orientation. Both ORFs are conserved among all currently known 'ambiviruses,' and one of them encodes a distinct viral RNA-directed RNA polymerase (RdRP), the hallmark gene of ribovirian kingdom Orthornavirae. However, 'ambivirus' genomes are circular and predicted to replicate via a rolling-circle mechanism. Their genomes are also predicted to form rod-like structures and contain ribozymes in various combinations in both sense and antisense orientations-features reminiscent of viroids, virusoids, ribozyvirian kolmiovirids, and yet-unclassified MGEs (such as 'epsilonviruses,' 'zetaviruses,' and some 'obelisks'). As a first step toward the formal classification of 'ambiviruses,' the International Committee on Taxonomy of Viruses (ICTV) recently approved the establishment of a novel ribovirian phylum, Ambiviricota, to accommodate an initial set of 20 members with well-annotated genome sequences.

Asunto(s)

Genoma Viral , Sistemas de Lectura Abierta , Viroides , Viroides/genética , Viroides/clasificación , Filogenia , ARN Viral/genética , Virus ARN/genética , Virus ARN/clasificación , Hongos/genética , Hongos/virología , ARN Polimerasa Dependiente del ARN/genética , Virus Fúngicos/genética , Virus Fúngicos/clasificación , Virus Fúngicos/aislamiento & purificación

RESUMEN

The cervicovaginal microbiome may contribute to human papillomavirus (HPV)-associated cervical carcinogenesis, but studies have been limited by low-resolution analysis methods. Using a high-resolution bioinformatics pipeline, we evaluated the relationship of the cervicovaginal microbiome with HPV and cervical intraepithelial neoplasia (CIN). The cervicovaginal microbiome of 186 women was characterized by sequencing 16S rRNA regions (V3-V4 and V5-V6) and annotated with the high-resolution ANCHOR pipeline. Samples were genotyped for HPV using the Roche-Cobas 4800 assay. We fitted logistic regression models using stepwise forward selection to select species (presence/absence) as correlates of CIN1+ and constructed a linear microbiome-based score using the regression coefficients. An HPV-based score was calculated from a separate logistic regression model to detect CIN1+ . Receiver operating characteristic curve analyses were performed; the area under the curve (AUC) and 95% confidence intervals (CI) were compared between scores. Overall, 66.7% of participants were HPV-positive. 77 unique species were identified: 8 using V3-V4, 48 using V5-V6, and 21 shared. Twelve species were retained via stepwise selection. The AUCs for the microbiome-, and HPV-based scores were 0.7656 (95% CI 0.6885-0.8426), and 0.7529 (95% CI 0.6855-0.8204), respectively. Bacterial species may be involved in cervical carcinogenesis as the microbiome- and HPV-based scores performed similarly for CIN1+ detection.

Asunto(s)

Carcinogénesis , Cuello del Útero , Microbiota , Papillomaviridae , Infecciones por Papillomavirus , ARN Ribosómico 16S , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Vagina , Humanos , Femenino , Infecciones por Papillomavirus/virología , Infecciones por Papillomavirus/microbiología , Infecciones por Papillomavirus/complicaciones , Adulto , Vagina/microbiología , Vagina/virología , Cuello del Útero/microbiología , Cuello del Útero/virología , Neoplasias del Cuello Uterino/virología , Neoplasias del Cuello Uterino/microbiología , Displasia del Cuello del Útero/microbiología , Displasia del Cuello del Útero/virología , Papillomaviridae/genética , Papillomaviridae/aislamiento & purificación , Papillomaviridae/clasificación , ARN Ribosómico 16S/genética , Persona de Mediana Edad , Genotipo , Bacterias/clasificación , Bacterias/aislamiento & purificación , Bacterias/genética , Adulto Joven , Virus del Papiloma Humano

RESUMEN

Evolution remains an incessant process in viruses, allowing them to elude the host immune response and induce severe diseases, impacting the diagnostic and vaccine effectiveness. Emerging and re-emerging diseases are among the significant public health concerns globally. The revival of dengue is mainly due to the potential for naturally arising mutations to induce genotypic alterations in serotypes. These transformations could lead to future outbreaks, underscoring the significance of studying DENV evolution in endemic regions. Predicting the emerging Dengue Virus (DENV) genome is crucial as the virus disrupts host cells, leading to fatal outcomes. Deep learning has been applied to predict dengue fever cases; there has been relatively less emphasis on its significance in forecasting emerging DENV serotypes. While Recurrent Neural Networks (RNN) were initially designed for modeling temporal sequences, our proposed DL-DVE generative and classification model, trained on complete genome data of DENV, transcends traditional approaches by learning semantic relationships between nucleotides in a continuous vector space instead of representing the contextual meaning of nucleotide characters. Leveraging 2000 publicly available DENV complete genome sequences, our Long Short-Term Memory (LSTM) based generative and Feedforward Neural Network (FNN) based classification DL-DVE model showcases proficiency in learning intricate patterns and generating sequences for emerging serotype of DENV. The generated sequences were analyzed along with available DENV serotype sequences to find conserved motifs in the genome through MEME Suite (version 5.5.5). The generative model showed an accuracy of 93 %, and the classification model provided insight into the specific serotype label, corroborated by BLAST search verification. Evaluation metrics such as ROC-AUC value 0.818, accuracy, precision, recall and F1 score, all to be around 99.00 %, demonstrating the classification model's reliability. Our model classified the generated sequences as DENV-4, exhibiting 65.99 % similarity to DENV-4 and around 63-65 % similarity with other serotypes, indicating notable distinction from other serotypes. Moreover, the intra-serotype divergence of sequences with a minimum of 90 % similarity underscored their uniqueness.

RESUMEN

Elite controllers (ECs) are an exceptional group of people living with HIV (PLWH) that control HIV replication without therapy. Among the mechanisms involved in this ability, natural killer (NK)-cells have recently gained much attention. We performed an in-deep phenotypic analysis of NK-cells to search for surrogate markers associated with the long term spontaneous control of HIV. Forty-seven PLWH (22 long-term EC [PLWH-long-term elite controllers (LTECs)], 15 noncontrollers receiving antiretroviral treatment [ART] [PLWH-onART], and 10 noncontrollers cART-naïve [PLWH-offART]), and 20 uninfected controls were included. NK-cells homeostasis was analyzed by spectral flow cytometry using a panel of 15 different markers. Data were analyzed using FCSExpress and R software for unsupervised multidimensional analysis. Six different subsets of NK-cells were defined on the basis of CD16 and CD56 expression, and the multidimensional analysis revealed the existence of 68 different NK-cells clusters based on the expression levels of the 15 different markers. PLWH-offART presented the highest disturbance of NK-cells homeostasis and this was not completely restored by long-term ART. Interestingly, long term spontaneous control of HIV (PLWH-LTEC group) was associated with a specific profile of NK-cells homeostasis disturbance, characterized by an increase of CD16dimCD56dim subset when compared to uninfected controls (UC) group and also to offART and onART groups (p < 0.0001 for the global comparison), an increase of clusters C16 and C26 when compared to UC and onART groups (adjusted p-value < 0.05 for both comparisons), and a decrease of clusters C10 and C20 when compared to all the other groups (adjusted p-value < 0.05 for all comparisons). These findings may provide clues to elucidate markers of innate immunity with a relevant role in the long-term control of HIV.

Asunto(s)

Infecciones por VIH , Células Asesinas Naturales , Humanos , Células Asesinas Naturales/inmunología , Infecciones por VIH/inmunología , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , Masculino , Adulto , Femenino , Persona de Mediana Edad , Citometría de Flujo , Sobrevivientes de VIH a Largo Plazo , Antígeno CD56/análisis , Biomarcadores , Inmunofenotipificación , Receptores de IgG , Fenotipo , VIH-1/inmunología , Proteínas Ligadas a GPI

RESUMEN

Previous studies have proposed alopecia areata (AA) as a potential outcome of COVID-19 infection among autoimmune diseases, yet the findings might be inconclusive and difficult to generalize due to limited sample sizes and evidence levels. Thus, we aimed to investigate in detail the long-term risk of AA following SARS-CoV-2 infection based on large, binational, general population-based cohort studies. Our study investigated the long-term AA risk after SARS-CoV-2 infection by analyzing bi-national, claim-based cohorts in South Korea and Japan: a Korean nationwide cohort (K-COV-N cohort; discovery cohort; total n = 10 027 506) and a Japanese claims-based cohort (JMDC cohort; validation cohort; total n = 12 218 680). AA was identified based on the international classification of diseases 10th revision code (L63) requiring at least three claims within 1 year. After exposure-driven propensity score matching, SARS-CoV-2 infection was associated with an increased risk of incident AA (aHR, 1.66; 95% CI, 1.38-1.99). This increased risk was observed and persisted for up to 6 months. A similar pattern was observed in the validation cohort. As modifiable factors, severe COVID-19 increased the risk of AA, whereas receiving two or more doses of the COVID-19 vaccine before infection decreased the risk of AA. Through a bi-national cohort study in South Korea and Japan, SARS-CoV-2 infection was associated with an elevated risk for incident AA in the aspect of long COVID.

Asunto(s)

Alopecia Areata , COVID-19 , Humanos , Alopecia Areata/epidemiología , COVID-19/epidemiología , COVID-19/complicaciones , República de Corea/epidemiología , Masculino , Femenino , Japón/epidemiología , Persona de Mediana Edad , Adulto , Estudios de Cohortes , Factores de Riesgo , Anciano , SARS-CoV-2 , Adulto Joven , Incidencia

RESUMEN

Acute gastroenteritis (AGE) represents a world public health relevant problem especially in children. Enteric viruses are the pathogens mainly involved in the episodes of AGE, causing about 70.00% of the cases. Apart from well-known rotavirus (RVA), adenovirus (AdV) and norovirus (NoV), there are various emerging viral pathogens potentially associated with AGE episodes. In this study, the presence of ten different enteric viruses was investigated in 152 fecal samples collected from children hospitalized for gastroenteritis. Real time PCR results showed that 49.3% of them were positive for viral detection with the following prevalence: norovirus GII 19.7%, AdV 15.8%, RVA 10.5%, human parechovirus (HPeV) 5.3%, enterovirus (EV) 3.3%, sapovirus (SaV) 2.6%. Salivirus (SalV), norovirus GI and astrovirus (AstV) 1.3% each, aichivirus (AiV) found in only one patient. In 38.2% of feces only one virus was detected, while co-infections were identified in 11.8% of the cases. Among young patients, 105 were ≤5 years old and 56.0% tested positive for viral detection, while 47 were >5 years old with 40.0% of them infected. Results obtained confirm a complex plethora of viruses potentially implicated in gastroenteritis in children, with some of them previously known for other etiologies but detectable in fecal samples. Subsequent studies should investigate the role of these viruses in causing gastroenteritis and explore the possibility that other symptoms may be ascribed to multiple infections.

Asunto(s)

COVID-19 , Coinfección , Heces , Gastroenteritis , Humanos , Gastroenteritis/virología , Gastroenteritis/epidemiología , Preescolar , Coinfección/virología , Coinfección/epidemiología , Heces/virología , Lactante , Italia/epidemiología , Niño , Masculino , Femenino , COVID-19/epidemiología , COVID-19/virología , Sapovirus/aislamiento & purificación , Sapovirus/genética , Virus/aislamiento & purificación , Virus/clasificación , Virus/genética , Prevalencia , Norovirus/aislamiento & purificación , Norovirus/genética , Adolescente , Virosis/epidemiología , Virosis/virología , Recién Nacido , SARS-CoV-2 , Rotavirus/aislamiento & purificación , Rotavirus/genética , Adenoviridae/aislamiento & purificación

RESUMEN

Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) primarily targets the respiratory system. Physiologically relevant human lung models are indispensable to investigate virus-induced host response and disease pathogenesis. In this study, we generated human induced pluripotent stem cell (iPSC)-derived alveolar organoids (AOs) using an established protocol that recapitulates the sequential steps of in vivo lung development. AOs express alveolar epithelial type II cell protein markers including pro-surfactant protein C and ATP binding cassette subfamily A member 3. Compared to primary human alveolar type II cells, AOs expressed higher mRNA levels of SARS-CoV-2 entry factors, angiotensin-converting enzyme 2 (ACE2), asialoglycoprotein receptor 1 (ASGR1) and basigin (CD147). Considering the localization of ACE2 on the apical side in AOs, we used three AO models, apical-in, sheared and apical-out for SARS-CoV-2 infection. All three models of AOs were robustly infected with the SARS-CoV-2 irrespective of ACE2 accessibility. Antibody blocking experiment revealed that ASGR1 was the main receptor for SARS-CoV2 entry from the basolateral in apical-in AOs. AOs supported the replication of SARS-CoV-2 variants WA1, Alpha, Beta, Delta, and Zeta and Omicron to a variable degree with WA1 being the highest and Omicron being the least. Transcriptomic profiling of infected AOs revealed the induction of inflammatory and interferon-related pathways with NF-κB signaling being the predominant host response. In summary, iPSC-derived AOs can serve as excellent human lung models to investigate infection of SARS-CoV-2 variants and host responses from both apical and basolateral sides.

Asunto(s)

COVID-19 , Células Madre Pluripotentes Inducidas , Humanos , SARS-CoV-2 , Enzima Convertidora de Angiotensina 2/metabolismo , ARN Viral , Pulmón , Organoides , Receptor de Asialoglicoproteína

RESUMEN

This study aims to assess the safety, virological, and clinical outcomes of convalescent plasma transfusion (CPT) in immunocompromised patients hospitalized for coronavirus disease 2019 (COVID-19). We conducted a retrospective multicenter cohort study that included all immunosuppressed patients with COVID-19 and RNAemia from May 2020 to March 2023 treated with CPT. We included 81 patients with hematological malignancies (HM), transplants, or autoimmune diseases (69% treated with anti-CD20). Sixty patients (74%) were vaccinated, and 14 had pre-CPT serology >264 BAU/mL. The median delay between symptom onset and CPT was 23 days [13-31]. At D7 post-CPT, plasma PCR was negative in 43/64 patients (67.2%), and serology became positive in 25/30 patients (82%). Post-CPT positive serology was associated with RNAemia negativity (p < 0.001). The overall mortality rate at D28 was 26%, being higher in patients with non-B-cell HM (62%) than with B-cell HM (25%) or with no HM (11%) (p = 0.02). Patients receiving anti-CD20 without chemotherapy had the lowest mortality rate (8%). Positive RNAemia at D7 was associated with mortality at D28 in univariate analysis (HR: 3.05 [1.14-8.19]). Eight patients had adverse events, two of which were severe but transient. Our findings suggest that CPT can abolish RNAemia and ameliorate the clinical course in immunocompromised patients with COVID-19.

Asunto(s)

COVID-19 , Neoplasias Hematológicas , Humanos , COVID-19/terapia , Transfusión de Componentes Sanguíneos , Sueroterapia para COVID-19 , Estudios de Cohortes , Plasma , Neoplasias Hematológicas/complicaciones , Neoplasias Hematológicas/terapia , Huésped Inmunocomprometido , Viremia

RESUMEN

In 2022, a series of human monkeypox cases in multiple countries led to the largest and most widespread outbreak outside the known endemic areas. Setup of proper genomic surveillance is of utmost importance to control such outbreaks. To this end, we performed Nanopore (PromethION P24) and Illumina (NextSeq. 2000) Whole Genome Sequencing (WGS) of a monkeypox sample. Adaptive sampling was applied for in silico depletion of the human host genome, allowing for the enrichment of low abundance viral DNA without a priori knowledge of sample composition. Nanopore sequencing allowed for high viral genome coverage, tracking of sample composition during sequencing, strain determination, and preliminary assessment of mutational pattern. In addition to that, only Nanopore data allowed us to resolve the entire monkeypox virus genome, with respect to two structural variants belonging to the genes OPG015 and OPG208. These SVs in important host range genes seem stable throughout the outbreak and are frequently misassembled and/or misannotated due to the prevalence of short read sequencing or short read first assembly. Ideally, standalone standard Illumina sequencing should not be used for Monkeypox WGS and de novo assembly, since it will obfuscate the structure of the genome, which has an impact on the quality and completeness of the genomes deposited in public databases and thus possibly on the ability to evaluate the complete genetic reason for the host range change of monkeypox in the current pandemic.

Asunto(s)

Genoma Viral , Metagenómica , Monkeypox virus , Mpox , Secuenciación de Nanoporos , Secuenciación Completa del Genoma , Humanos , Genoma Viral/genética , Metagenómica/métodos , Secuenciación de Nanoporos/métodos , Mpox/epidemiología , Mpox/virología , Monkeypox virus/genética , Monkeypox virus/aislamiento & purificación , Secuenciación Completa del Genoma/métodos , Nanoporos , ADN Viral/genética , Secuenciación de Nucleótidos de Alto Rendimiento/métodos

RESUMEN

A genome, composed of a precisely ordered sequence of four nucleotides (ATCG), encompasses a multitude of specific genome features like AAA motif. Mutations occurring within a genome disrupt the sequential order and composition of these features, thereby influencing the evolutionary trajectories and yielding variants. The evolutionary relatedness between a variant and its ancestor can be estimated by assessing evolutionary distances across a spectrum of genome features. This study develops a novel, alignment-free algorithm that considers both the sequential order and composition of genome features, enabling computation of the Fréchet distance (Fr) across multiple genome features to quantify the evolutionary status of a variant. Integrating this algorithm with an artificial recurrent neural network (RNN) reveals the quantitative evolutionary trajectory and origin of SARS-CoV-2, a puzzle unsolved by alignment-based phylogenetics. The RNN generates the evolutionary trajectory from Fr data at two levels: genome sequence mutations and organism variants. At the genome sequence level, SARS-CoV-2 evolutionarily shortens its genome to enhance its infectious capacity. Mutating signature features, such as TTA and GCT, increases its infectious potential and drives its evolution. At the organism level, variants mutating a single biomarker possess low infectious potential. However, mutating multiple markers dramatically increases their infectious capacity, propelling the COVID-19 pandemic. SARS-CoV-2 likely originates from mink coronavirus variants, with its origin trajectory traced as follows: mink, cat, tiger, mouse, hamster, dog, lion, gorilla, leopard, bat, and pangolin. Together, mutating multiple signature features and biomarkers delineates the evolutionary trajectory of mink-origin SARS-CoV-2, leading to the COVID-19 pandemic.

Asunto(s)

COVID-19 , Quirópteros , Animales , Humanos , Perros , Ratones , SARS-CoV-2/genética , COVID-19/genética , Pandemias , Visón/genética , Genoma Viral , Pangolines , Inteligencia Artificial , Filogenia

RESUMEN

A large-scale outbreak of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) occurred in Shanghai, China, in early December 2022. To study the incidence and characteristics of otitis media with effusion (OME) complicating SARS-CoV-2, we collected 267 middle ear effusion (MEE) samples and 172 nasopharyngeal (NP) swabs from patients. The SARS-CoV-2 virus was detected by RT-PCR targeting. The SARS-CoV-2 virus, angiotensin-converting enzyme 2 (ACE2), and transmembrane serine protease 2 (TMPRSS2) expression in human samples was examined via immunofluorescence. During the COVID-19 epidemic in 2022, the incidence of OME (3%) significantly increased compared to the same period from 2020 to 2022. Ear symptoms in patients with SARS-CoV-2 complicated by OME generally appeared late, even after a negative NP swab, an average of 9.33 ± 6.272 days after COVID-19 infection. The SARS-CoV-2 virus was detected in MEE, which had a higher viral load than NP swabs. The insertion rate of tympanostomy tubes was not significantly higher than in OME patients in 2019-2022. Virus migration led to high viral loads in MEE despite negative NP swabs, indicating that OME lagged behind respiratory infections but had a favorable prognosis. Furthermore, middle ear tissue from adult humans coexpressed the ACE2 receptor for the SARS-CoV-2 virus and the TMPRSS2 cofactors required for virus entry.

Asunto(s)

COVID-19 , Otitis Media con Derrame , Adulto , Humanos , SARS-CoV-2 , COVID-19/complicaciones , Enzima Convertidora de Angiotensina 2 , China/epidemiología

RESUMEN

Antiviral therapy based on neuraminidase (oseltamivir) or polymerase (baloxavir marboxil) inhibitors plays an important role in the management of influenza infections. However, the emergence of drug resistance and the uncontrolled inflammatory response are major limitations in the treatment of severe influenza disease. Protectins D1 (PD1) and DX (PDX), part of a family of pro-resolving mediators, have previously demonstrated anti-influenza activity as well as anti-inflammatory properties in various clinical contexts. Herein, we synthetized a series of simplified PDX analogs and assessed their in vitro antiviral activity against influenza A(H1N1) viruses, including oseltamivir- and baloxavir-resistant variants. In ST6GalI-MDCK cells, the PDX analog AN-137B reduced viral replication in a dose-dependent manner with IC50 values of 23.8 for A/Puerto Rico/8/1934 (H1N1) and between 32.6 and 36.7 µM for susceptible and resistant A(H1N1)pdm09 viruses. In MTS-based cell viability experiments, AN-137B showed a 50% cellular cytotoxicity (CC50 ) of 638.7 µM with a resulting selectivity index of 26.8. Of greater importance, the combination of AN-137B with oseltamivir or baloxavir resulted in synergistic and additive in vitro effects, respectively. Treatment of lipopolysaccharide (LPS)-stimulated macrophages with AN-137B resulted in a decrease of iNOS activity as shown by the reduction of nitrite production, suggesting an anti-inflammatory effect. In conclusion, our results indicate that the protectin analog AN-137B constitutes an interesting therapeutic modality against influenza A virus, warranting further evaluation in animal models.

Asunto(s)

Dibenzotiepinas , Ácidos Docosahexaenoicos , Subtipo H1N1 del Virus de la Influenza A , Virus de la Influenza A , Gripe Humana , Morfolinas , Piridonas , Triazinas , Animales , Humanos , Oseltamivir/farmacología , Oseltamivir/uso terapéutico , Antivirales/farmacología , Antivirales/uso terapéutico , Gripe Humana/tratamiento farmacológico , Antiinflamatorios/uso terapéutico , Farmacorresistencia Viral , Neuraminidasa

RESUMEN

Human papillomaviruses (HPVs) cause more than 4.5% of all cancer in the world and more than half of these cases are attributed to human papillomavirus type 16 (HPV16). Prophylactic vaccines are available but antiviral drugs are not. Novel targets for therapy are urgently needed. Alternative RNA splicing is extensively used by HPVs to express all their genes and HPV16 is no exception. This process must function to perfection since mis-splicing could perturb the HPV gene expression program by altering mRNA levels or by generating dysfunctional mRNAs. Cis-acting RNA elements on the viral mRNAs and their cognate cellular trans-acting factors control papillomavirus RNA splicing. The precise but delicate nature of the splicing process renders splicing sensitive to interference. As such, papillomavirus RNA splicing is a potential target for therapy. Here we summarize our current understanding of cis-acting HPV16 RNA elements that control HPV16 mRNA splicing via cellular proteins and discuss how they may be exploited as targets for therapy to papillomavirus infections and cancer.

Asunto(s)

Neoplasias , Proteínas Oncogénicas Virales , Infecciones por Papillomavirus , Humanos , Proteínas Oncogénicas Virales/genética , Empalme del ARN , ARN Mensajero/genética , ARN Mensajero/metabolismo , ARN Viral/genética , ARN Viral/metabolismo , Virus del Papiloma Humano , Infecciones por Papillomavirus/tratamiento farmacológico

RESUMEN

This book chapter presents a concise overview of SARS-CoV-2, the virus responsible for the COVID-19 pandemic. It explores viral classification based on morphology and nucleic acid composition with a focus on DNA and RNA viruses, the SARS-CoV-2 structure including the structural as well as nonstructural proteins in detail, and the viral replication mechanisms. The chapter then delves into the characteristics and diversity of coronaviruses, particularly SARS-CoV-2, highlighting its similarities with other beta-coronaviruses. The replication and transcription complex, RNA elongation, and capping, as well as the role of accessory proteins in viral replication and modulation of the host immune response is discussed extensively.

Asunto(s)

COVID-19 , SARS-CoV-2 , Humanos , Animales , COVID-19/metabolismo , Pandemias , Estadios del Ciclo de Vida , Estructuras Virales/metabolismo

RESUMEN

Utilizing multiplex real time polymerase chain reaction (RT-PCR) for rapid diagnosis of gastroenteritis, enables simultaneous detection of multiple pathogens. A comparative analysis of disease characteristics was conducted between cases with single and multiple viruses. Rotavirus vaccine was introduced in 2010, reaching a 70% coverage in 2 years. All rectal swabs collected from diarrheic children (<5 years) between December 2017 and March 2022 were included. Detection of the same viruses within 2 months was considered a single episode. Episodes with positive stool bacterial PCR were excluded. A total of 5879 samples were collected, revealing 86.9% (1509) with single virus detection and 13.1% (227) with multiple viruses. The most frequent combination was rotavirus and norovirus (27.8%), these infections followed a winter-spring seasonality akin to rotavirus. Children with multivirus infections exhibited higher immunodeficiency (OR 2.06) rates, but lower food allergy (OR 0.45) and prematurity rates (OR 0.55) compared to single infections. Greater disease severity, evaluated by the Vesikari score, was observed in multivirus episodes (p < 0.001, OR 1.12). Multivirus infections accounted for 13.1% of symptomatic cases in hospitalized young children. Despite vaccination efforts, rotavirus remained prominent, frequently in co-infections with norovirus. Overall, multivirus infections were linked to more severe diseases than single virus cases.

Asunto(s)

Gastroenteritis , Norovirus , Infecciones por Rotavirus , Rotavirus , Virus , Niño , Humanos , Lactante , Preescolar , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Gastroenteritis/diagnóstico , Gastroenteritis/epidemiología , Rotavirus/genética , Infecciones por Rotavirus/diagnóstico , Infecciones por Rotavirus/epidemiología , Virus/genética , Norovirus/genética , Reacción en Cadena de la Polimerasa Multiplex , Técnicas y Procedimientos Diagnósticos , Heces

RESUMEN

The incidence of human papillomavirus (HPV) associated oropharyngeal squamous cell carcinoma (OPSCC) is increasing among elderly (≥70 years) patients and the optimal treatment approach is not known. In this study, we aimed to determine disease and toxicity outcomes in an elderly HPV-OPSCC population primarily treated with a chemoradiation (CRT) approach. We identified 70 elderly HPV-OPSCC patients who were treated with either surgery, radiotherapy, or CRT between 2011 and 2021. Time-to-event analysis for overall survival (OS), progression-free survival (PFS), and local control (LC) were conducted using the Kaplan-Meier method. Univariate and multivariable cox regression models were used to estimate the hazard ratio associated with covariates. The median follow-up for our cohort was 43.9 months. Of the 70 elderly patients, 55 (78.6%) receive CRT and 15 (22.4%) received RT alone. Two patients underwent TORS resection. Of the 55 patients treated with CRT, the most common systemic agents were weekly carboplatin/taxol (n = 18), cetuximab (n = 17), and weekly cisplatin (n = 11). The 5-year OS, PFS, and LC were 57%, 52%, and 91%, respectively. On univariate analysis, Eastern Cooperative Oncology Group performance status and Charlson Comorbidity Index (CCI) were significant predictors of OS, while on multivariate analysis only CCI was a significant predictor of OS (p = 0.006). The rate of late peg tube dependency, osteoradionecrosis, and aspiration was 10%, 4%, and 4%, respectively. Definitive local therapy in elderly HPV-OPSCC patients is associated with excellent LC and a low rate of late toxicities. Prospective studies are needed to further stratify subgroups of elderly patients who may benefit from aggressive definitive local therapy.

Asunto(s)

Neoplasias de Cabeza y Cuello , Neoplasias Orofaríngeas , Infecciones por Papillomavirus , Humanos , Anciano , Virus del Papiloma Humano , Infecciones por Papillomavirus/complicaciones , Neoplasias Orofaríngeas/radioterapia , Neoplasias Orofaríngeas/patología , Carcinoma de Células Escamosas de Cabeza y Cuello , Estudios Retrospectivos