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Mosquito-borne Zika virus (ZIKV) typically causes a mild and self-limiting illness known as Zika fever, which often is accompanied by maculopapular rash, headache, and myalgia. During the current outbreak in South America, ZIKV infection during pregnancy has been hypothesized to cause microcephaly and other diseases. The detection of ZIKV in fetal brain tissue supports this hypothesis. Because human infections with ZIKV historically have remained sporadic and, until recently, have been limited to small-scale epidemics, neither the disease caused by ZIKV nor the molecular determinants of virulence and/or pathogenicity have been well characterized. Here, we describe a small animal model for wild-type ZIKV of the Asian lineage. Using mice deficient in interferon α/β and Ɣ receptors (AG129 mice), we report that these animals were highly susceptible to ZIKV infection and disease, succumbing within seven to eight days. Rapid viremic dissemination was observed in visceral organs and brain; but only was associated with severe pathologies in the brain and muscle. Finally, these results were consistent across challenge routes, age of mice, and inoculum doses. These data represent a mouse model for ZIKV that is not dependent on adapting ZIKV to intracerebral passage in mice. Foot pad injection of AG129 mice with ZIKV represents a biologically relevant model for studying ZIKV infection and disease development following wild-type virus inoculation without the requirement for adaptation of the virus or intracerebral delivery of the virus. This newly developed Zika disease model can be exploited to identify determinants of ZIKV virulence and reveal molecular mechanisms that control the virus-host interaction, providing a framework for rational design of acute phase therapeutics and for vaccine efficacy testing.

Mosquito-borne Zika virus (ZIKV) typically causes a mild and self-limiting illness known as Zika fever. Since its recent emergence in 2014 in the American continent, ZIKV infection during pregnancy has been closely associated with a wide range of congenital abnormalities. To date, no vaccines or antivirals are publicly available. We developed Zika virus-like particles (VLPs) and evaluated their immunogenicity and protective efficacy in mouse models. ZIKV VLPs (ZIKVLPs) formulated with alum were injected into 6-8-week-old interferon deficient AG129 mice as well as wild type BALB/c mice. Control mice received PBS/alum. Animals were challenged with 200 PFU (>1000 AG129 LD50s) of ZIKV strain H/PF/2013. All vaccinated mice survived with no morbidity or weight loss while control animals either died at 9 days post challenge (AG129) or had increased viremia (BALB/c). Neutralizing antibodies were observed in all ZIKVLP vaccinated mice. The role of neutralizing antibodies in protecting mice was demonstrated by passive transfer. Our findings demonstrate the protective efficacy of the ZIKVLP vaccine and highlight the important role that neutralizing antibodies play in protection against ZIKV infection.

Background Dengue fever is a major public health problem in Colombia. A fever surveillance study was conducted for evaluation of the clinical, epidemiological, and molecular patterns of dengue, prior to Chikungunya and Zika epidemics. Methods In November 2011–February 2014, a passive facility-based surveillance was implemented in Santa Cruz Hospital, Medellin, and enrolled eligible febrile patients between 1 and 65 years-of-age. Acute and convalescent blood samples were collected 10–21 days apart and tested for dengue using IgM/IgG ELISA. RNA was extracted for serotyping using RT-PCR on acute samples and genotyping was performed by sequencing. Results Among 537 febrile patients enrolled during the study period, 29% ( n  = 155) were identified to be dengue-positive. Only 7% of dengue cases were hospitalized, but dengue-positive patients were 2.6 times more likely to be hospitalized, compared to non-dengue cases, based on a logistic regression. From those tested with RT-PCR ( n  = 173), 17 were dengue-confirmed based on PCR and/or virus isolation showing mostly DENV-3 ( n  = 9) and DENV-4 ( n  = 7) with 1 DENV-1. Genotyping results showed that: DENV-1 isolate belongs to the genotype V or American/African genotype; DENV-3 isolates belong to genotype III; and DENV-4 isolates belong to the II genotype and specifically to the IIb sub-genotype or linage. Conclusions Our surveillance documented considerable dengue burden in Santa Cruz comuna during non-epidemic years, and genetic diversity of circulating DENV isolates, captured prior to Chikungunya epidemic in 2014 and Zika epidemic in 2015. Our study findings underscore the need for continued surveillance and monitoring of dengue and other arboviruses and serve as epidemiological and molecular evidence base for future studies to assess changes in DENV transmission in Medellin, given emerging and re-emerging arboviral diseases in the region.

Background: Zika virus (ZIKV) is a mosquito-borne flavivirus associated with severe neurological disease, including congenital Zika syndrome (CZS) following utero infection and Guillain–Barré syndrome in adults. The 2015–2016 epidemic in the Americas highlighted the profound maternal and neonatal consequences of ZIKV infection. Although reported transmission has declined, ongoing circulation of competent vectors and population susceptibility sustain a substantial risk of future outbreaks, underscoring the need for effective vaccines. Methods: We developed a recombinant Modified Vaccinia Ankara (MVA)-based vaccine candidate expressing the ZIKV pre-membrane (prM) and envelope (E) proteins and evaluated its immunogenicity and protective efficacy in interferon receptor-deficient AG129 mice. Results: Vaccination induced strong humoral and cellular immune responses and conferred significant protection against viral replication in key target organs, including the brain and testes, following ZIKV challenge. Conclusions: These preclinical findings support further development of this MVA-based ZIKV vaccine as a promising strategy to prevent ZIKV infection and its associated neurological complications.

BACKGROUND: Current treatments for Alzheimer’s disease primarily address symptoms, as no definitive therapeutic targets have been identified. OBJECTIVES: This study aims to conduct a virtual screening of small molecules and synthesize and evaluate one of the most promising candidates for Alzheimer’s therapy. METHODS: Using AutoDock Vina, compounds with drug-like properties were docked against key proteins implicated in Alzheimer's pathology: β-Secretase, γ-Secretase, Pin1, and Cdk5. The molecule with the highest in silico affinity (PubChem ID: 84378305) was synthesized and evaluated experimentally. Cytotoxicity and neuroprotective effects were assessed using the MTT assay in the presence of the Aβ25-35 peptide. RESULTS: Four candidate molecules showed strong binding affinity, ranging from -6.8 to -9.1 kcal/mol. The results showed that when SK-N-SH cells were simultaneously treated with Aß25-35 peptide (5 µM) and compound 84378305 (0,1 µM), the molecule exhibited significant neuroprotection (33%) after the 48 h of incubation. CONCLUSION: Findings indicate that this lead compound exhibits potential neuroprotective activity, highlighting its promise as a candidate for further development in Alzheimer’s disease treatment.

Background Upon the pandemic transitioning into a new phase, research into the immune pathophysiology of severe and critical coronavirus disease 2019 has become increasingly crucial. Such studies are pivotal in shaping advanced treatment strategies and driving the development of innovative therapeutics, including more effective vaccines targeting the virus. High-risk comorbidities and pre-existing immunocompromised states have been identified as significant factors contributing to increased susceptibility to severe coronavirus disease 2019. Moreover, cases of severe infections, particularly those characterized by relapses or viral persistence, provide invaluable insights into the evolving behavior and dynamics of this pathogen. Cases series presentation We report three cases involving mixed-race Colombian female patients aged 58, 35, and 63 years who experienced multiple episodes of coronavirus disease 2019 infection, with the most recent episode progressing to critical illness. These cases were characterized by relapses or persistent infections, and genomic analyses consistently identified the Omicron severe acute respiratory syndrome coronavirus 2 lineage as the causative variant. Notably, individuals with underlying immunosuppressive conditions developed severe acute respiratory syndrome coronavirus 2 infections that were more severe, leading to fatal outcomes that included acute respiratory distress syndrome, multiorgan dysfunction, and death. In contrast, one vaccinated patient with significant comorbidities exhibited persistent critical coronavirus disease 2019 but responded positively to treatment with tocilizumab. Conclusions The key takeaway is the critical need for continued investigation into coronavirus disease 2019 among individuals with high-risk comorbidities and those undergoing immunosuppressive therapy. Recurrent episodes of infection, including cases marked by relapses or persistent viral presence in these populations, create conditions conducive to viral replication and adaptation. Such environments may potentially act as breeding grounds for the emergence of significant new viral mutations.

[This corrects the article DOI: 10.1371/journal.pntd.0004682.].

Latin America is one of the regions in which the COVID-19 pandemic has had a stronger impact, with more than 72 million reported infections and 1.6 million deaths until June 2022. Since this region is ecologically diverse and is affected by enormous social inequalities, efforts to identify genomic patterns of the circulating SARS-CoV-2 genotypes are necessary for the suitable management of the pandemic. To contribute to the genomic surveillance of the SARS-CoV-2 in Latin America, we extended the number of SARS-CoV-2 genomes available from the region by sequencing and analyzing the viral genome from COVID-19 patients from seven countries (Argentina, Brazil, Costa Rica, Colombia, Mexico, Bolivia and Peru). Subsequently, we analyzed the genomes circulating mainly during 2021 including records from GISAID database from Latin America. A total of 1534 genome sequences were generated from seven countries, demonstrating the laboratory and bioinformatics capabilities for genomic surveillance of pathogens that have been developed locally. For Latin America, patterns regarding several variants associated with multiple re-introductions, a relatively low percentage of sequenced samples, as well as an increment in the mutation frequency since the beginning of the pandemic, are in line with worldwide data. Besides, some variants of concern (VOC) and variants of interest (VOI) such as Gamma, Mu and Lambda, and at least 83 other lineages have predominated locally with a country-specific enrichments. This work has contributed to the understanding of the dynamics of the pandemic in Latin America as part of the local and international efforts to achieve timely genomic surveillance of SARS-CoV-2. Competing Interest Statement The authors have declared no competing interest.

In the industry, the robotic gas metal arc welding (GMAW) process has a huge range of applications, including in the automotive sector, construction companies, the shipping industry, and many more. Automatic quality inspection in robotic welding is crucial because it ensures the uniformity, strength, and safety of welded joints without the need for constant human intervention. Detecting defects in real time prevents defective products from reaching advanced production stages, reducing reprocessing costs. In addition, the use of materials is optimized by avoiding defective welds that require rework, contributing to cleaner production. This paper presents a novel dataset of robot GMAW images for experimental purposes, including human-expert segmentation and human knowledge labeling regarding the different errors that may appear in welding. In addition, it tests an automatic segmentation approach for robot GMAW quality assessment. The results presented confirm that automatic segmentation is comparable to human segmentation, guaranteeing a correct welding quality assessment to provide feedback on the robot welding process.