Heavy-element production in a compact object merger observed by JWST.

The mergers of binary compact objects such as neutron stars and black holes are of central interest to several areas of astrophysics, including as the progenitors of gamma-ray bursts (GRBs)1, sources of high-frequency gravitational waves (GWs)2 and likely production sites for heavy-element nucleosynthesis by means of rapid neutron capture (the r-process)3. Here we present observations of the exceptionally bright GRB 230307A. We show that GRB 230307A belongs to the class of long-duration GRBs associated with compact object mergers4-6 and contains a kilonova similar to AT2017gfo, associated with the GW merger GW170817 (refs. 7-12). We obtained James Webb Space Telescope (JWST) mid-infrared imaging and spectroscopy 29 and 61 days after the burst. The spectroscopy shows an emission line at 2.15 microns, which we interpret as tellurium (atomic mass A = 130) and a very red source, emitting most of its light in the mid-infrared owing to the production of lanthanides. These observations demonstrate that nucleosynthesis in GRBs can create r-process elements across a broad atomic mass range and play a central role in heavy-element nucleosynthesis across the Universe.

Polyphenol Composition by HPLC-DAD-(ESI-)MS/MS and Bioactivities of Extracts from Grape Agri-Food Wastes.

BACKGROUND: Grape agri-food wastes, such as skin, seeds, and other discarded by-products, contain phytochemical compounds that offer potential health benefits. METHODS: This study aimed to investigate the polyphenol composition and bioactivities of different extracts obtained from grape marc and seeds, with the goal of exploring their potential for application as natural food additives. RESULTS: Regardless of the extraction method used (dynamic maceration, ultrasound-assisted extraction (UAE), and microwave-assisted extraction (MAE)), all extracts exhibited relatively high concentrations of phenolic compounds. The chemical characterization of the extracts revealed the presence of specific compounds and chemical groups associated with each extraction methodology. Moreover, the extracts displayed satisfactory antioxidant activities, especially in inhibiting lipoperoxidation as assessed by the TBARS assay. Additionally, the extracts demonstrated effective inhibition against different strains of bacteria and fungi known as food contaminants. Taken together, these findings indicate that those extracts have the potential to be tested as natural antioxidants and preservatives with sustainable origins in food and beverage systems. Among the extraction methods evaluated, traditional maceration and UAE provided extracts with the highest antioxidant and antimicrobial activities. CONCLUSIONS: Our results suggest the opportunity to explore grape marc and seeds discarded by the winery industry in Portugal as natural sources of bioactive compounds, which could be employed as functional food ingredients or technological additives. The valorization of grape biowastes offers a promising strategy to reduce waste and harness their potential health benefits.

Gestational protein restriction alters early amygdala neurochemistry in male offspring.

BACKGROUND: Gestational protein intake restriction-induced long-lasting harmful outcomes in the offspring's organs and systems. However, few studies have focused on this event's impact on the brain's structures and neurochemical compounds. AIM: The present study investigated the effects on the amygdala neurochemical composition and neuronal structure in gestational protein-restricted male rats' offspring. METHODS: Dams were maintained on isocaloric standard rodent laboratory chow with regular protein [NP, 17%] or low protein content [LP, 6%]. Total cells were quantified using the Isotropic fractionator method, Neuronal 3D reconstruction, and dendritic tree analysis using the Golgi-Cox technique. Western blot and high-performance liquid chromatography performed neurochemical studies. RESULTS: The gestational low-protein feeding offspring showed a significant decrease in birth weight up to day 14, associated with unaltered brain weight in youth or adult progenies. The amygdala cell numbers were unchanged, and the dendrites length and dendritic ramifications 3D analysis in LP compared to age-matched NP progeny. However, the current study shows reduced amygdala content of norepinephrine, epinephrine, and dopamine in LP progeny. These offspring observed a significant reduction in the amygdala glucocorticoid (GR) and mineralocorticoid (MR) receptor protein levels. Also corticotrophin-releasing factor (CRF) amygdala protein content was reduced in 7 and 14-day-old LP rats. CONCLUSION: The observed amygdala neurochemical changes may represent adaptation during embryonic development in response to elevated fetal exposure to maternal corticosteroid levels. In this way, gestational malnutrition stress can alter the amygdala's neurochemical content and may contribute to known behavioral changes induced by gestational protein restriction.

A kilonova following a long-duration gamma-ray burst at 350 Mpc.

Gamma-ray bursts (GRBs) are divided into two populations1,2; long GRBs that derive from the core collapse of massive stars (for example, ref. 3) and short GRBs that form in the merger of two compact objects4,5. Although it is common to divide the two populations at a gamma-ray duration of 2 s, classification based on duration does not always map to the progenitor. Notably, GRBs with short (≲2 s) spikes of prompt gamma-ray emission followed by prolonged, spectrally softer extended emission (EE-SGRBs) have been suggested to arise from compact object mergers6-8. Compact object mergers are of great astrophysical importance as the only confirmed site of rapid neutron capture (r-process) nucleosynthesis, observed in the form of so-called kilonovae9-14. Here we report the discovery of a possible kilonova associated with the nearby (350 Mpc), minute-duration GRB 211211A. The kilonova implies that the progenitor is a compact object merger, suggesting that GRBs with long, complex light curves can be spawned from merger events. The kilonova of GRB 211211A has a similar luminosity, duration and colour to that which accompanied the gravitational wave (GW)-detected binary neutron star (BNS) merger GW170817 (ref. 4). Further searches for GW signals coincident with long GRBs are a promising route for future multi-messenger astronomy.

First Genomic Evidence of a Henipa-like Virus in Brazil.

The viral genus Henipavirus includes two highly virulent zoonotic viruses of serious public health concern. Hendra henipavirus and Nipah henipavirus outbreaks are restricted to Australia and Southeast Asia, respectively. The Henipavirus genus comprises mostly bat-borne viruses, but exceptions have already been described as novel viruses with rodents and shrews as reservoir animals. In the Americas, scarce evidence supports the circulation of these viruses. In this communication, we report a novel henipa-like virus from opossums (Marmosa demerarae) from a forest fragment area in the Peixe-Boi municipality, Brazil, after which the virus was named the Peixe-Boi virus (PBV). The application of next-generation sequencing and metagenomic approach led us to discover the original evidence of a henipa-like virus genome in Brazil and South America and the original description of a henipa-like virus in marsupial species. These findings emphasize the importance of further studies to characterize PBV and clarify its ecology, impact on public health, and its relationship with didelphid marsupials and henipaviruses.

Effectiveness of multimodal circuit exercises for chronic musculoskeletal pain in older adults: A randomized controlled trial protocol.

Studies have shown that musculoskeletal pain is one of the most prevalent health conditions that affects many individuals worldwide. In older adults, persistent pain is a widely prevalent and a disabling condition of multiple contributing factors: physical, mental, and social. Consequently, their quality of life is hampered. We aimed to analyze the effectiveness of a multimodal circuit exercise program on chronic musculoskeletal pain and disabling in older adults. This is a randomized parallel study (two arms) with blinded outcome assessments. The participants' recruitment will be done by a non-probabilistic sampling resulting from invitations to Basic Health Units (BHU). The sample size estimation indicated 164 participants. Participants will be allocated, by means of a randomization process, to one of two groups (82 for each group): Experimental Group (multimodal circuit exercise) or Control Group (cycle of multidisciplinary lectures on pain and stretching exercise). All analyses will be processed using the RStudio software, with significance when a p-value of 2 tails is less than 5% (p<0.05). Statistical analysis will follow the intention to treat. Trial registration: ClinicalTrials.gov NCT04719130, January 20, 2021.

Balance Exercise Circuit for fall prevention in older adults: a randomized controlled crossover trial.

Objectives: This study aimed to assess the immediate and short-term effects of the Balance Exercise Circuit (BEC) on muscle strength, postural balance, and quality of life, with the aim of preventing falls in older adults. Methods: Twenty-two volunteers participated in this randomized controlled crossover study. Group A performed BEC training in the initial 3 months and received no intervention in the following 3 months. Group B received no intervention during the first 3 months and then participated in BEC training for the next 3 months. In addition, participants were followed for an additional 3 months. Muscle strength, postural balance, functional mobility, and quality of life were assessed, respectively, using an isokinetic dynamometer, force platform, TUG test, and the WHOQOL. Results: After 3 months of training, Group A presented improved balance and rate of force development (RFD), while Group B presented improvements in RFD, TUG performance, and WHOQOL physical and psychological domains. Regarding the short-term effects, the participants maintained the training effects in WHOQOL balance, RFD, and the social domain. In addition, the number of falls decreased during follow-up. Conclusion: The BEC intervention improved muscle strength, postural balance, and quality of life in older adults, in addition to reducing the risk of falls. Trial registration: Brazilian Registry of Clinical Trials (ReBEC) - RBR-5nvrwm.

Absence of Anti-RBD Antibodies in SARS-CoV-2 Infected or Naive Individuals Prior to Vaccination with CoronaVac Leads to Short Protection of Only Four Months Duration.

The COVID-19 pandemic is the biggest public health threat facing the world today. Multiple vaccines have been approved; however, the emergence of viral variants such as the recent Omicron raises the possibility of booster doses to achieve adequate protection. In Brazil, the CoronaVac (Sinovac, Beijing, China) vaccine was used; however, it is important to assess the immune response to this vaccine over time. This study aimed to monitor the anti-SARS-CoV-2 antibody responses in those immunized with CoronaVac and SARS-CoV-2 infected individuals. Samples were collected between August 2020 and August 2021. Within the vaccinated cohort, some individuals had a history of infection by SARS-CoV-2 prior to immunization, while others did not. We analyzed RBD-specific and neutralizing-antibodies. Anti-RBD antibodies were detected in both cohorts, with a peak between 45-90 days post infection or vaccination, followed by a steady decline over time. In those with a previous history of COVID-19, a higher, longer, more persistent response was observed. This trend was mirrored in the neutralization assays, where infection, followed by immunization, resulted in higher, longer lasting responses which were conditioned on the presence of levels of RBD antibodies right before the vaccination. This supports the necessity of booster doses of CoronaVac in due course to prevent serious disease.

Translation and cross-cultural adaptation of the Childhood Bladder and Bowel Dysfunction Questionnaire (CBBDQ)

Abstract Objective: To translate and cross-culturally adapt the Childhood Bladder and Bowel Dysfunction Questionnaire (CBBDQ) for use in Brazilian Portuguese. The CBBDQ is an 18-item tool covering 10 bladder and 8 bowel symptoms that was developed for use with children of 5 to 12 years of age with bowel and bladder dysfunction (BBD). The instrument has already been validated for use in Dutch and English. Method: In the process of translation and cultural adaptation from English to Portuguese, the CBBDQ was submitted to undergo the required steps as established by the international methodological criteria: forward translation, synthesis, back-translation, expert panel review and pre-testing. Results: Ninety-three parents of children with lower urinary tract dysfunction answered the questionnaire. The mean age of the children was 7.6 ± 2.1 years and 54 were female. Internal consistency was excellent, with a Cronbach's alpha of 0.91 to 0.96. Additionally, reliability was high, with an intraclass correlation coefficient of 0.94 (95%CI: 0.85-0.93; p < 0.0001). Conclusion: The translation and cultural adaptation of the CBBDQ enabled a quantitative evaluation of bladder and bowel symptoms to be performed in Brazilian children. The scores achieved allow the severity of BBD to be evaluated, as well as the patient's progress during treatment. The use of this questionnaire in clinical practice and research will allow more consistent data on BBD to be obtained.

Reporter Virus Neutralization Test Evaluation for Dengue and Zika Virus Diagnosis in Flavivirus Endemic Area.

Reporter virus neutralization test (RVNT) has been used as an alternative to the more laborious and time-demanding conventional PRNT assay for both DENV and ZIKV. However, few studies have investigated how these techniques would perform in epidemic areas with the circulation of multiple flavivirus. Here, we evaluate the performance of ZIKV and DENV Rluc RVNT and ZIKV mCh RVNT assays in comparison to the conventional PRNT assay against patient sera collected before and during ZIKV outbreak in Brazil. These samples were categorized into groups based on (1) acute and convalescent samples according to the time of disease, and (2) laboratorial diagnostic results (DENV and ZIKV RT-PCR and IgM-capture ELISA). Our results showed that DENV Rluc assay presented 100% and 78.3% sensitivity and specificity, respectively, with 93.3% accuracy, a similar performance to the traditional PRNT. ZIKV RVNT90, on the other hand, showed much better ZIKV antibody detection performance (around nine-fold higher) when compared to PRNT, with 88% clinical sensitivity. Specificity values were on average 76.8%. Even with these results, however, ZIKV RVNT90 alone was not able to reach a final diagnostic conclusion for secondary infection in human samples due to flavivirus cross reaction. As such, in regions where the flavivirus differential diagnosis represents a challenge, we suggest the establishment of a RVNT panel including other flaviviruses circulating in the region, associated with the other serological techniques such as IgM ELISA and the investigation of seroconversion, in order to help define an accurate diagnostic conclusion using serology.

The Usefulness of a Duplex RT-qPCR during the Recent Yellow Fever Brazilian Epidemic: Surveillance of Vaccine Adverse Events, Epizootics and Vectors.

From 2016 to 2018, Brazil faced the biggest yellow fever (YF) outbreak in the last 80 years, representing a risk of YF reurbanization, especially in megacities. Along with this challenge, the mass administration of the fractionated YF vaccine dose in a naïve population brought another concern: the possibility to increase YF adverse events associated with viscerotropic (YEL-AVD) or neurological disease (YEL-AND). For this reason, we developed a quantitative real time RT-PCR (RT-qPCR) assay based on a duplex TaqMan protocol to distinguish broad-spectrum infections caused by wild-type yellow fever virus (YFV) strain from adverse events following immunization (AEFI) by 17DD strain during the vaccination campaign used to contain this outbreak. A rapid and more accurate RT-qPCR assay to diagnose YFV was established, being able to detect even different YFV genotypes and geographic strains that circulate in Central and South America. Moreover, after testing around 1400 samples from human cases, non-human primates and mosquitoes, we detected just two YEL-AVD cases, confirmed by sequencing, during the massive vaccination in Brazilian Southeast region, showing lower incidence than AEFI as expected.

Transcription Landscape of the Early Developmental Biology in Pigs.

Since pre- and postnatal development are programmed during early prenatal life, studies addressing the complete transcriptional landscape during organogenesis are needed. Therefore, we aimed to disentangle differentially expressed (DE) genes between fetuses (at 35 days old) and embryos (at 25 days old) through RNA-sequencing analysis using the pig as model. In total, 1705 genes were DE, including the top DE IBSP, COL6A6, HBE1, HBZ, HBB, and NEUROD6 genes, which are associated with developmental transition from embryos to fetuses, such as ossification, skeletal muscle development, extracellular matrix organization, cardiovascular system, erythrocyte differentiation, and neuronal system. In pathway analysis, embryonic development highlighted those mainly related to morphogenic signaling and cell interactions, which are crucial for transcriptional control during the establishment of the main organs in early prenatal development, while pathways related to myogenesis, neuronal development, and cardiac and striated muscle contraction were enriched for fetal development, according to the greater complexity of organs and body structures at this developmental stage. Our findings provide an exploratory and informative transcriptional landscape of pig organogenesis, which might contribute to further studies addressing specific developmental events in pigs and in other mammals.

Translation and cross-cultural adaptation of the Childhood Bladder and Bowel Dysfunction Questionnaire (CBBDQ).

OBJECTIVE: To translate and cross-culturally adapt the Childhood Bladder and Bowel Dysfunction Questionnaire (CBBDQ) for use in Brazilian Portuguese. The CBBDQ is an 18-item tool covering 10 bladder and 8 bowel symptoms that was developed for use with children of 5 to 12 years of age with bowel and bladder dysfunction (BBD). The instrument has already been validated for use in Dutch and English. METHOD: In the process of translation and cultural adaptation from English to Portuguese, the CBBDQ was submitted to undergo the required steps as established by the international methodological criteria: forward translation, synthesis, back-translation, expert panel review and pre-testing. RESULTS: Ninety-three parents of children with lower urinary tract dysfunction answered the questionnaire. The mean age of the children was 7.6±2.1 years and 54 were female. Internal consistency was excellent, with a Cronbach's alpha of 0.91 to 0.96. Additionally, reliability was high, with an intraclass correlation coefficient of 0.94 (95%CI: 0.85-0.93; p<0.0001). CONCLUSION: The translation and cultural adaptation of the CBBDQ enabled a quantitative evaluation of bladder and bowel symptoms to be performed in Brazilian children. The scores achieved allow the severity of BBD to be evaluated, as well as the patient's progress during treatment. The use of this questionnaire in clinical practice and research will allow more consistent data on BBD to be obtained.

Educational Interventions to Improve Dental Anatomy Carving Ability of Dental Students: A Systematic Review.

This systematic review aimed to identify the level of impact of educational strategies for teaching tooth carving on the carving ability of undergraduate dental students. The PubMed-NCBI, Cochrane-CENTRAL, LILACS, Ibecs, BBO, Web of Science, and Scopus databases were searched in May 2019, for randomized controlled trials (RCTs) and two-arm non-randomized studies of interventions (NRSI) addressing educational interventions toward the dental carving of undergraduate students. Studies from the year 2000 until the search date, written in English, Portuguese, and Spanish were included. Study screening and data extraction were performed in duplicate and blinded. The data were presented narratively, considering the dental carving ability of students the primary outcome. The risk of bias was assessed using the RoB tool 2.0 and ROBINS-I, and the level of evidence was determined with GRADE. Of 3,574 studies, 6 were included, with 3 RCTs and 3 NRSIs. Very low level of evidence was provided from the NRSIs that flipped classroom (1 study; n = 140) and a student-driven revised module (1 study; n = 264) improved the carving ability of students. Additionally, there was moderate evidence of online complementary material (1 RCT; n = 30) and reinforcement class improving the carving ability of students (1 RCT; n = 29). The replacement of traditional classes by an instructional DVD (1 RCT; n = 73) and assessment of carving projects through digital systems (1 NRSI; n = 79) did not enhance the carving ability of students. Study design, risk of bias, and imprecision downgraded the level of evidence. There was a very low to moderate evidence on the effectiveness of student-driven educational approaches and complementary classes of dental anatomy in improving the dental carving ability of students.

Applying an association weight matrix in weighted genomic prediction of boar taint compounds.

Biological information regarding markers and gene association may be used to attribute different weights for single nucleotide polymorphism (SNP) in genome-wide selection. Therefore, we aimed to evaluate the predictive ability and the bias of genomic prediction using models that allow SNP weighting in the genomic relationship matrix (G) building, with and without incorporating biological information to obtain the weights. Firstly, we performed a genome-wide association studies (GWAS) in data set containing single- (SL) or a multi-line (ML) pig population for androstenone, skatole and indole levels. Secondly, 1%, 2%, 5%, 10%, 30% and 50% of the markers explaining the highest proportions of the genetic variance for each trait were selected to build gene networks through the association weight matrix (AWM) approach. The number of edges in the network was computed and used to derive weights for G (AWM-WssGBLUP). The single-step GBLUP (ssGBLUP) and weighted ssGBLUP (WssGBLUP) were used as standard scenarios. All scenarios presented predictive abilities different from zero; however, the great overlap in their confidences interval suggests no differences among scenarios. Most of scenarios of based on AWM provide overestimations for skatole in both SL and ML populations. On the other hand, the skatole and indole prediction were no biased in the ssGBLUP (S1) in both SL and ML populations. Most of scenarios based on AWM provide no biased predictions for indole in both SL and ML populations. In summary, using biological information through AWM matrix and gene networks to derive weights for genomic prediction resulted in no increase in predictive ability for boar taint compounds. In addition, this approach increased the number of analyses steps. Thus, we can conclude that ssGBLUP is most appropriate for the analysis of boar taint compounds in comparison with the weighted strategies used in the present work.

Translation and cross-cultural adaptation of 14-item Mediterranean Diet Adherence Screener and low-fat diet adherence questionnaire.

BACKGROUND AND AIMS: The Mediterranean diet and the low-fat diet are recognized as cardioprotective dietary patterns, and the use of validated instruments that quickly identify adherence to these diets is very useful in the daily practice of the nutritionist. Our aim was to translate and cross-culturally adapt the 14-point Mediterranean Diet Adherence Screener (MEDAS) and a 9-item quantitative score of compliance with the low-fat diet (low-fat diet questionnaire) to the Brazilian Portuguese language. METHODS: The process of translation and cultural adaptation was conducted in six stages: initial translation, synthesis of translations, back-translation, proof of cross-cultural equivalence, pre-final version testing, and final evaluation of the cultural adaptation process. Interviews and assessments were administered to 30 nutritionists, and to 51 healthy participants and 50 individuals at cardiovascular risk. MEDAS ranges from 0 (minimum) to 14 (maximum) points and a total score ≥ 10 points was considered for high adherence to MedDiet. Low-fat diet questionnaire ranges from 0 (minimum) to 9 (maximum) points and a total score ≥ 6 points was considered for high adherence to a diet restricted in fat. RESULTS: MEDAS and low-fat diet questionnaire were translated, synthetized and then back-translated, and few grammatical and/or semantic changes were required. About 24 participants suggested at least one modification in low-fat diet questionnaire's questions/terms, and 28 participants suggested at least one change in MEDAS items. The process produced a valid version of both the MEDAS and low-fat diet questionnaire in the Brazilian Portuguese language. Participants showed an average MEDAS questionnaire of 5.3 ± 2.5 points, and an average low-fat diet questionnaire of 5.9 ± 1.9 points. Nutritionists showed higher means of low-fat diet scores when compared to healthy and at high cardiovascular risk individuals (7.1 ± 1.3, 5.6 ± 2 and 5.4 ± 1.9, respectively [P < 0.0001]) but not for MEDAS questionnaire. With a cutoff of ≥10 points, 2.3% (95% CI 0.78-6.52) of the participants showed high adherence to MedDiet based on MEDAS score, and with a cutoff of ≥6 points, 58% (95% CI 49.5-66.1) of the participants showed high adherence to a diet restricted in fat based on the low-fat diet questionnaire. CONCLUSIONS: MEDAS and low-fat diet questionnaire were successfully translated to the Portuguese language. Regarding the results from questionnaires applied to our sample, in general, poor adherence was found for both Mediterranean and low-fat diet.

Seed morphobiometry, morphology of germination and emergence of quinoa seeds 'BRS Piabiru'.

Quinoa, classified as a pseudocereal, presents greater nutritional value compared to traditional cereals. Considering the potential for cultivation presented by the species and the benefits of studying plant morphology and morphobiometry, this paper describes seed and seedling morphobiometric characteristics of quinoa (Chenopodium quinoa Willd.) cultivar BRS Piabiru during germination and emergence. To evaluate seed morphobiometry the 1000-seeds weight, moisture content, seed morphological characterization and the tetrazolium test were performed. The morphological characterization of germination and seedling emergence were performed by periodic observations during the development, allowing the description using pictures and drawings. Quinoa seeds cv. BRS Piabiru present an average diameter of 2.05 mm and 1.07 width. 1000-seeds weight of 2.68 g and moisture content of 11%. Externally, quinoa seeds present the pericarp as testa, the hilum and the raphe and, internally, the embryonic axis (cotyledons, radicle and hypocotyl-radicle), perisperm and endosperm. The germination is characterized as epigeal, phanerocotylar type, with radicle protrusion at 3 hours after sowing and complete formed seedlings at 24 hours after sowing. Emergence occurs at 9 days after sowing and plants are completely formed at 12 days after sowing.

l-Arginine supplementation of gilts during early gestation modulates energy sensitive pathways in pig conceptuses.

Dietary l-arginine (ARG) supplementation has been studied as a nutritional strategy to improve reproductive performance of pregnant sows, since arginine is a conditionally essential amino acid. However, reports addressing the molecular mechanisms that mediate supplementation effects on embryos and fetuses development are still scarce. Therefore, we aimed to evaluate the effects of 1.0% ARG supplementation of commercial pregnant gilts on genes and proteins from energy metabolism and antioxidant defense pathways in embryos and fetuses. We also analyzed the global transcriptome profile of 25- and 35-day-old conceptuses. At Day 25, we observed a lower abundance of phospho-AMP-activated protein kinase (phospho-AMPK) protein and downregulation of oxidative phosphorylation system genes in ARG embryos. On the other hand, ARG fetuses showed greater expression of MLST8 and lower expression of MTOR genes, in addition to lower abundance of phospho-AMPK and phospho-mammalian target of rapamycin (phospho-mTOR) proteins. Transcriptome analysis at Day 35 did not present differentially expressed genes. For the antioxidant defense pathway, no differences were found between CON and ARG conceptuses, only trends. In general, supplementation of gilts with 1.0% ARG during early gestation affects energy sensitive pathways in 25- and 35-day conceptuses; however, no effects of supplementation were found on the antioxidative defense pathway in 25-day embryos.

Zika structural genes determine the virulence of African and Asian lineages.

The Asian lineage of Zika virus (ZIKV) is responsible for the recent epidemics in the Americas and severe disease, whereas the African lineage of ZIKV has not been reported to cause epidemics or severe disease. We constructed a cDNA infectious clone (IC) of an African ZIKV strain, which, together with our previously developed Asian ZIKV strain IC, allowed us to engineer chimeric viruses by swapping the structural and non-structural genes between the two lineages. Recombinant parental and chimeric viruses were analyzed in A129 and newborn CD1 mouse models. In the A129 mice, the African strain developed higher viremia, organ viral loading, and mortality rate. In CD1 mice, the African strain exhibited a higher neurovirulence than the Asian strain. A chimeric virus containing the structural genes from the African strain is more virulent than the Asian strain, whereas a chimeric virus containing the non-structural genes from the African strain exhibited a virulence comparable to the Asian strain. These results suggest that (i) African strain is more virulent than Asian strain and (ii) viral structural genes primarily determine the virulence difference between the two lineages in mouse models. Other factors may contribute to the discrepancy between the mouse and epidemic results.