Passive Immunotherapy of Cynomolgus Monkeys with Anti-Rotavirus IgY.

Immunoglobulins Y (IgY) purified from egg yolks of hens represents an attractive, cost-effective alternative for the development of new diagnostic and therapeutic platforms. In this study, we evaluated the therapeutic efficacy of rotavirus-specific IgY in a cynomolgus monkey (Macaca fascicularis) model. Animals were experimentally infected with human rotavirus Group A (RVA), the most common cause of severe acute diarrhoea among young children worldwide. Animals were administered human RVA (3.1 × 107 FFU/mL) by oral gavage, challenged with 2.5 mg of anti-RVA IgY orally, and monitored for five days according to clinical, haematological and biochemical parameters; serum electrolyte levels; viral shedding; and histopathological changes. Immunotherapy with anti-RVA IgY had a protective effect against severe rotavirus-induced enteritis in four of the ten treated monkeys, as evidenced by histopathological findings. Although only one animal had diarrhoea, all but one exhibited virus shedding regardless of the treatment.

Association between detection rate of norovirus GII and climatic factors in the Northwest Amazon region.

Worldwide, approximately one fifth of all cases of diarrhea are associated with norovirus, mainly in children, with a defined seasonality in temperate climates, but seasonal dynamics are less known in tropical climates. The objective was to investigate the impact of external clinical, epidemiological, and climatic factors on norovirus detection rates in samples from children under 5 years of age from Roraima, the Amazon region of Brazil. A total of 941 samples were included. According to climatic factors, we observed correlations between external climatic factors and weekly positivity rates, where temperature (P = 0.002), relative humidity (P = 0.0005), absolute humidity (P < 0.0001) and wind speed had the strongest effect (P = 0.0006). The Brazilian Amazon region presents a typical and favorable scenario for the persistence, expansion, and distribution of viral gastroenteritis. Importance: This study is important as it will serve as a basis for studies carried out in Brazil and Latin American countries on the epidemiological importance, seasonality, climate change, antigenic diversity, among other factors in the circulation of gastroenteric virus.

Evaluation of Extraction Methods to Detect Noroviruses in Ready-to-Eat Raw Milk Minas Artisanal Cheese.

This study aimed to assess two homogenization methods to recover norovirus from Minas artisanal cheese (MAC) made with raw bovine milk obtained from four microregions of the Minas Gerais state, Brazil, with different ripening times and geographical and abiotic characteristics. For this purpose, 33 fiscal samples were artificially contaminated with norovirus GI and GII, and Mengovirus (MgV), used as an internal process control (IPC). TRIzol® reagent and Proteinase K homogenization methods were evaluated for all samples were then subjected to RNA extraction using viral magnetic beads and RT-qPCR Taqman® for viral detection/quantification. Proteinase K method showed better efficiency results for both norovirus GI and GII, with means recovery efficiency of 45.7% (95% CI 34.3-57.2%) and 41.4% (95% CI 29.1-53.6%), respectively, when compared to TRIzol method (16.6% GI, 95% CI 8.4-24.9%, and 12.3% GII, 95% CI 7.0-17.6%). The limits of detection for norovirus GI and GII for this method were 101GC/g and 103GC/g, respectively, independent of cheese origin. MgV was detected and revealed in 100% success rate in all types of cheese, with mean recovery efficiency of 25.6% for Proteinase K, and 3.8% for the TRIzol method. According to cheese origin, Triangulo Mineiro MAC had the highest mean recovery rates for the three viral targets surveyed (89% GI, 87% GII, and 51% MgV), while Serro MAC showed the lowest rates (p < 0.001). Those results indicate that the proteinase K adapted method is suitable for norovirus GI and GII detection in MAC and corroborated MgV as an applicable IPC to be used during the process.

Assessment of Gastroenteric Viruses in Marketed Bivalve Mollusks in the Tourist Cities of Rio de Janeiro, Brazil, 2022.

This study investigated the prevalence and genetic diversity of gastroenteric viruses in mussels and oysters in Rio de Janeiro, Brazil. One hundred and thirty-four marketed bivalve samples were obtained between January and December 2022. The viral analysis was performed according to ISO/TS 15216, and the screening revealed the detection of norovirus GII/GI (40.3%), sapovirus (SaV; 12.7%), human mastadenovirus (7.5%), and rotavirus A (RVA; 5.9%). In total, 44.8% (60) of shellfish samples tested positive for one or more viruses, 46.7% (28/60) of the positive samples tested positive for a single viral agent, 26.7% (16) tested positive for two viral agents, 8.3% (5) for three viral agents, and 13.3% (8) for four viral agents. Additionally, three mussel samples were contaminated with the five investigated viruses (5%, 3/60). Norovirus GII showed the highest mean viral load (3.4 × 105 GC/g), followed by SaV (1.4 × 104 GC/g), RVA (1.1 × 104 GC/g), human mastadenovirus (3.9 × 103 GC/g), and norovirus GI (6.7 × 102 GC/g). Molecular characterization revealed that the recovered norovirus strains belonged to genotypes GII.2, GII.6, GII.9, GII.17, and GII.27; SaV belonged to genotypes GI.1 and GIV.1; RVA to genotypes G6, G8, P[8]-III, and human mastadenovirus to types F40 and F41. The GII.27 norovirus characterized in this study is the only strain of this genotype reported in Brazil. This study highlights the dissemination and diversity of gastroenteric viruses present in commercialized bivalves in a touristic area, indicating the potential risk to human health and the contribution of bivalves in the propagation of emerging pathogens.

Microbiome and virome on indoor surfaces of an Antarctic research ship.

BACKGROUND: Few studies have focused on microbial diversity in indoor environments of ships, as well as the role of the microbiome and its ecological interconnections. In this study, we investigated the microbiome and virome present on the internal surfaces of a polar ship in different stages (beginning, during, and at the end) of the Brazilian Antarctic expedition in order to evaluate abundance of microorganisms in different periods. OBJECTIVES AND METHODS: We used shotgun metagenomic analysis on pooled samples from sampling surfaces in the ship's interior to track the microbial diversity. FINDINGS: Considering the total fraction of the microbiome, the relative abundance of bacteria, eukaryotes, viruses, and archaea was 83.7%, 16.2%, 0.04%, and 0.002%, respectively. Proteobacteria was the most abundant bacterial phyla, followed by Firmicutes, Actinobacteria, and Bacteroidetes. Concerning the virome, the greatest richness of viral species was identified during the middle of the trip, including ten viral families after de novo assembly: Autographiviridae, Chrysoviridae, Genomoviridae, Herelleviridae, Myoviridae, Partitiviridae, Podoviridae, Potyviridae, Siphoviridae, and Virgaviridae. MAIN CONCLUSIONS: This study contributed to the knowledge of microbial diversity in naval transportation facilities, and variations in the abundance of microorganisms probably occurred due to factors such as the number of passengers and activities on the ship.

G6P[8] Rotavirus a Possessing a Wa-like VP3 Gene from a Child with Acute Gastroenteritis Living in the Northwest Amazon Region.

The introduction of rotavirus A (RVA) vaccines has considerably reduced the RVA-associated mortality among children under 5 years of age worldwide. The ability of RVA to reassort gives rise to different combinations of surface proteins G (glycoprotein, VP7) and P (protease sensitive, VP4) RVA types infecting children. During the epidemiological surveillance of RVA in the Northwest Amazon region, an unusual rotavirus genotype G6P[8] was detected in feces of a 2-year-old child with acute gastroenteritis (AGE) that had been vaccinated with one dose of Rotarix® (RV1). The G6P[8] sample had a DS-1-like constellation with a Wa-like VP3 gene mono-reassortment similar to equine-like G3P[8] that has been frequently detected in Brazil previously. The results presented here reinforce the evolutionary dynamics of RVA and the importance of constant molecular surveillance.

Circulation of Vaccine-derived Rotavirus G1P[8] in a Vulnerable Child Cohort in Rio de Janeiro.

BACKGROUND: The expansion of rotavirus (RV) immunization in several countries reduced the burden of acute diarrheal disease (ADD) and diarrhea-associated mortality. Although community transmission of live attenuated monovalent rotavirus vaccine (G1P[8] RV1) virus has been demonstrated in children and household contacts, fecal shedding of these strains in neonates and infants under six weeks of age has never been demonstrated. The objective of the study was to assess ADD and rotavirus vaccine strain shedding before and after immunization through 24 months of age. METHODS: This was a prospective cohort study in a low-resource community in which stool samples were collected from neonates from 15 to 45 days of age every 2 weeks, after both doses of G1P[8] RV1, and in subsequent ADD episodes until 2 years of age. RV was detected and genotyped in stool samples by RT-PCR. RESULTS: We enrolled 242 participants who were followed for an average of 23 months. The specific prevalence of G1P[8] RV1 virus was 3.3% in neonates and infants less than six weeks of age, 50% after the first dose, and 25.6% after the second dose. Among the 70 participants with ADD, G1P[8] RV1 virus was identified in only one participant (1.4% prevalence). CONCLUSIONS: In vaccinated children, there were no breakthrough infections with G1P[8] RV1 and ADD was rare supporting high vaccine effectiveness. We observed G1P[8] RV1 virus shedding among neonates and infants before the first vaccine dose, providing evidence of transmission of the vaccine strain from immunized children to those who are not yet vaccinated.

Microbiome and virome on indoor surfaces of an Antarctic research ship

BACKGROUND Few studies have focused on microbial diversity in indoor environments of ships, as well as the role of the microbiome and its ecological interconnections. In this study, we investigated the microbiome and virome present on the internal surfaces of a polar ship in different stages (beginning, during, and at the end) of the Brazilian Antarctic expedition in order to evaluate abundance of microorganisms in different periods. OBJECTIVES AND METHODS We used shotgun metagenomic analysis on pooled samples from sampling surfaces in the ship's interior to track the microbial diversity. FINDINGS Considering the total fraction of the microbiome, the relative abundance of bacteria, eukaryotes, viruses, and archaea was 83.7%, 16.2%, 0.04%, and 0.002%, respectively. Proteobacteria was the most abundant bacterial phyla, followed by Firmicutes, Actinobacteria, and Bacteroidetes. Concerning the virome, the greatest richness of viral species was identified during the middle of the trip, including ten viral families after de novo assembly: Autographiviridae, Chrysoviridae, Genomoviridae, Herelleviridae, Myoviridae, Partitiviridae, Podoviridae, Potyviridae, Siphoviridae, and Virgaviridae. MAIN CONCLUSIONS This study contributed to the knowledge of microbial diversity in naval transportation facilities, and variations in the abundance of microorganisms probably occurred due to factors such as the number of passengers and activities on the ship.

Molecular Epidemiology of Sapovirus in Children Living in the Northwest Amazon Region.

Sapovirus is an important etiological agent of acute gastroenteritis (AGE), mainly in children under 5 years old living in lower-income communities. Eighteen identified sapovirus genotypes have been observed to infect humans. The aim of this study was to identify sapovirus genotypes circulating in the Amazon region. Twenty-eight samples were successfully genotyped using partial sequencing of the capsid gene. The genotypes identified were GI.1 (n = 3), GI.2 (n = 7), GII.1 (n = 1), GII.2 (n = 1), GII.3 (n = 5), GII.5 (n = 1), and GIV.1 (n = 10). The GIV genotype was the most detected genotype (35.7%, 10/28). The phylogenetic analysis identified sapovirus genotypes that had no similarity with other strains reported from Brazil, indicating that these genotypes may have entered the Amazon region via intense tourism in the Amazon rainforest. No association between histo-blood group antigen expression and sapovirus infection was observed.

Epidemiology of enteric virus infections in children living in the Amazon region.

OBJECTIVES: To verify the frequency of viruses causing acute gastroenteritis (AGE) in association with the histo-blood group antigen (HBGA) and Rotarix™ vaccination coverage in children from the Amazon region. DESIGN: Fecal and saliva samples were collected from children with AGE (n = 485) and acute respiratory infection (ARI) (n = 249) clinical symptoms. Rotavirus A (RVA), norovirus, human adenovirus (HAdV), and sapovirus (SaV) were verified in feces by molecular detection. Saliva samples were used for HBGA phenotyping/FUT3 genotyping. Blood group types, clinical aspects and Rotarix™ RVA vaccination data were recorded. RESULTS: Norovirus remained the most prevalently detected cause of AGE (38%, 184/485 and ARI 21.3%, 53/249). High HAdV frequencies were observed in AGE children (28.6%, 139/485) and ARI children (37.3%, 93/249). RVA was the third most prevalent virus causing AGE (22.7%, 110/485 and ARI 19.3%, 48/249) and a low RV1 coverage (61%, 448/734) was verified. The SaV frequencies were lower (7.2%, 35/485 for AGE and 6.8%, 17/249 for ARI). Secretor children were HBGA susceptible to HAdV infection (OR 1.5, 95% CI 1.0-2.3; P = 0.04) but not to RVA, norovirus or SaV infection. CONCLUSIONS: Norovirus could be considered the main etiological agent of AGE. No association was verified for HBGA susceptibility to RVA, norovirus and SaV. Secretor children showed a slight susceptibility to HAdV infection and the Le (a-b-) heterogeneous SNPs on the FUT3 gene.

Should COVID-19 be branded to viral thrombotic fever?

Coronaviruses can cause a diverse array of clinical manifestations, from fever with symptoms of the common cold to highly lethal severe acute respiratory syndrome (SARS) and middle east respiratory syndrome (MERS). SARS-CoV-2, the coronavirus discovered in Hubei province, China, at the end of 2019, became known worldwide for causing coronavirus disease 2019 (COVID-19). Over one year's time period, the scientific community has produced a large bulk of knowledge about this disease and countless reports about its immune-pathological aspects. This knowledge, including data obtained in postmortem studies, points unequivocally to a hypercoagulability state. However, the name COVID-19 tells us very little about the true meaning of the disease. Our proposal is more comprehensive; it intends to frame COVID-19 in more clinical terminology, making an analogy to viral haemorrhagic fever (VHF). Thus, we found irrefutable evidence in the current literature that COVID-19 is the first viral disease that can be branded as a viral thrombotic fever. This manuscript points out that SARS-CoV-2 goes far beyond pneumonia or SARS. COVID-19 infections promote remarkable interactions among the endothelium, coagulation, and immune response, building up a background capable of promoting a "thrombotic storm," much more than a "cytokine storm." The importance of a viral protease called main protease (Mpro) is highlighted as a critical component for its replication in the host cell. A deeper analysis of this protease and its importance on the coagulation system is also discussed for the first time, mainly because of its similarity with the thrombin and factor Xa molecules, as recently pointed out by structural comparison crystallographic structures.

First report of human astrovirus MLB2 in Brazil detected in feces of children with acute gastroenteritis living in the state of Roraima, Northern Brazil.

Human astrovirus (HAstV) 1-8 and highly divergent HAstVMLB1-3 genotypes have been detected in children both with and without acute gastroenteritis (AGE). One hundred and seventy fecal samples from children (≤5 years old) living in the Amazon region were evaluated for the presence of HAstV1-8, HAstV MLB1-3 and HAstVVA1-3, using an usual RT-PCR protocol and a new protocol with specific primers designed to detect HAstVMLB1-3. HAstVMLB1 and HAstV MLB2, as well as the HAstV3 and 5 genotypes were detected. HAstVMLB1-2 genotype was detected for the first time in Brazil at a frequency of 3.5% (6/170).

FUT2, Secretor Status and FUT3 Polymorphisms of Children with Acute Diarrhea Infected with Rotavirus and Norovirus in Brazil.

Host susceptibility according to human histo-blood group antigens (HBGAs) is widely known for norovirus infection, but is less described for rotavirus. Due to the variable HBGA polymorphism among populations, we aimed to evaluate the association between HBGA phenotypes (ABH, Lewis and secretor status) and susceptibility to rotavirus and norovirus symptomatic infection, and the polymorphisms of FUT2 and FUT3, of children from southeastern Brazil. Paired fecal-buccal specimens from 272 children with acute diarrhea were used to determine rotavirus/norovirus genotypes and HBGAs phenotypes/genotypes, respectively. Altogether, 100 (36.8%) children were infected with rotavirus and norovirus. The rotavirus P[8] genotype predominates (85.7%). Most of the noroviruses (93.8%) belonged to genogroup II (GII). GII.4 Sydney represented 76% (35/46) amongst five other genotypes. Rotavirus and noroviruses infected predominantly children with secretor status (97% and 98.5%, respectively). However, fewer rotavirus-infected children were Lewis-negative (8.6%) than the norovirus-infected ones (18.5%). FUT3 single nucleotide polymorphisms (SNP) occurred mostly at the T59G > G508A > T202C > C314T positions. Our results reinforce the current knowledge that secretors are more susceptible to infection by both rotavirus and norovirus than non-secretors. The high rate for Lewis negative (17.1%) and the combination of SNPs, beyond the secretor status, may reflect the highly mixed population in Brazil.

Simple, Low-Cost and Long-Lasting Film for Virus Inactivation Using Avian Coronavirus Model as Challenge.

The COVID-19 infection, caused by SARS-CoV-2, is inequitably distributed and more lethal among populations with lower socioeconomic status. Direct contact with contaminated surfaces has been among the virus sources, as it remains infective up to days. Several disinfectants have been shown to inactivate SARS-CoV-2, but they rapidly evaporate, are flammable or toxic and may be scarce or inexistent for vulnerable populations. Therefore, we are proposing simple, easy to prepare, low-cost and efficient antiviral films, made with a widely available dishwashing detergent, which can be spread on hands and inanimate surfaces and is expected to maintain virucidal activity for longer periods than the current sanitizers. Avian coronavirus (ACoV) was used as model of the challenge to test the antivirus efficacy of the proposed films. Polystyrene petri dishes were covered with a thin layer of detergent formula. After drying, the films were exposed to different virus doses for 10 min and virus infectivity was determined using embryonated chicken eggs, and RNA virus quantification in allantoic fluids by RT-qPCR. The films inactivated the ACoV (ranging from 103.7 to 106.7 EID50), which is chemically and morphologically similar to SARS-CoV-2, and may constitute an excellent alternative to minimize the spread of COVID-19.

Epidemiology of Shigella infections and diarrhea in the first two years of life using culture-independent diagnostics in 8 low-resource settings.

Culture-independent diagnostics have revealed a larger burden of Shigella among children in low-resource settings than previously recognized. We further characterized the epidemiology of Shigella in the first two years of life in a multisite birth cohort. We tested 41,405 diarrheal and monthly non-diarrheal stools from 1,715 children for Shigella by quantitative PCR. To assess risk factors, clinical factors related to age and culture positivity, and associations with inflammatory biomarkers, we used log-binomial regression with generalized estimating equations. The prevalence of Shigella varied from 4.9%-17.8% in non-diarrheal stools across sites, and the incidence of Shigella-attributable diarrhea was 31.8 cases (95% CI: 29.6, 34.2) per 100 child-years. The sensitivity of culture compared to qPCR was 6.6% and increased to 27.8% in Shigella-attributable dysentery. Shigella diarrhea episodes were more likely to be severe and less likely to be culture positive in younger children. Older age (RR: 1.75, 95% CI: 1.70, 1.81 per 6-month increase in age), unimproved sanitation (RR: 1.15, 95% CI: 1.03, 1.29), low maternal education (<10 years, RR: 1.14, 95% CI: 1.03, 1.26), initiating complementary foods before 3 months (RR: 1.10, 95% CI: 1.01, 1.20), and malnutrition (RR: 0.91, 95% CI: 0.88, 0.95 per unit increase in weight-for-age z-score) were risk factors for Shigella. There was a linear dose-response between Shigella quantity and myeloperoxidase concentrations. The burden of Shigella varied widely across sites, but uniformly increased through the second year of life and was associated with intestinal inflammation. Culture missed most clinically relevant cases of severe diarrhea and dysentery.

Rotavirus A in Brazil: Molecular Epidemiology and Surveillance during 2018-2019.

Rotavirus A (RVA) vaccines succeeded in lowering the burden of acute gastroenteritis (AGE) worldwide, especially preventing severe disease and mortality. In 2019, Brazil completed 13 years of RVA vaccine implementation (Rotarix™) within the National Immunization Program (NIP), and as reported elsewhere, the use of Rotarix™ in the country has reduced childhood mortality and morbidity due to AGE. Even though both marketed vaccines are widely distributed, the surveillance of RVA causing AGE and the monitoring of circulating genotypes are important tools to keep tracking the epidemiological scenario and vaccines impact. Thus, our study investigated RVA epidemiological features, viral load and G and P genotypes circulation in children and adults presenting AGE symptoms in eleven states from three out of five regions in Brazil. By using TaqMan®-based one-step RT-qPCR, we investigated a total of 1536 stool samples collected from symptomatic inpatients, emergency department visits and outpatients from January 2018 to December 2019. G and P genotypes of RVA-positive samples were genetically characterized by multiplex RT-PCR or by nearly complete fragment sequencing. We detected RVA in 12% of samples, 10.5% in 2018 and 13.7% in 2019. A marked winter/spring seasonality was observed, especially in Southern Brazil. The most affected age group was children aged >24-60 months, with a positivity rate of 18.8% (p < 0.05). Evaluating shedding, we found a statistically lower RVA viral load in stool samples collected from children aged up to six months compared to the other age groups (p < 0.05). The genotype G3P[8] was the most prevalent during the two years (83.7% in 2018 and 65.5% in 2019), and nucleotide sequencing of some strains demonstrated that they belonged to the emergent equine-like G3P[8] genotype. The dominance of an emergent genotype causing AGE reinforces the need for continuous epidemiological surveillance to assess the impact of mass RVA immunization as well as to monitor the emergence of novel genotypes.

Rotavirus A shedding and HBGA host genetic susceptibility in a birth community-cohort, Rio de Janeiro, Brazil, 2014-2018.

Recent studies have investigated whether the human histo-blood group antigen (HBGAs) could affect the effectiveness of the oral rotavirus vaccines, suggesting secretor positive individuals develop a more robust response. We investigated the Rotavirus A (RVA) shedding in association with the host susceptibility profile in children from a birth community-cohort in Rio de Janeiro, Brazil, from 2014 to 2018. A total of 132 children were followed-up between 0 to 11-month-old, stool samples were collected before/after the 1st/2nd RV1 vaccination doses and saliva samples were collected during the study. RVA shedding was screened by RT-qPCR and G/P genotypes determined by multiplex RT-PCR and/or Sanger nucleotide sequencing. The sequencing indicated an F167L amino acid change in the RV1 VP8* P[8] in 20.5% of shedding follow-ups and these mutant subpopulations were quantified by pyrosequencing. The HBGA/secretor status was determined and 80.3% of the children were secretors. Twenty-one FUT2 gene SNPs were identified and two new mutations were observed. The mutant F167L RV1 VP8* P[8] was detected significantly more in Le (a+b+) secretors (90.5%) compared to non-secretors and even to secretors Le (a-b+) (9.5%). The study highlights the probable association between RV1 shedding and HBGAs as a marker for evaluating vaccine strain host susceptibility.

Human Bocavirus genotypes 1 and 2 detected in younger Amazonian children with acute gastroenteritis or respiratory infections, respectively.

OBJECTIVES: This study aimed to verify the frequency, genotypes, and etiological role of Human Bocavirus (HBoV) in younger Amazonian children with either acute gastroenteritis (AGE) or respiratory infections (ARI). The influence of Rotarix™ vaccination and co-infection status was also investigated. DESIGN: HBoV quantitative polymerase chain reaction (qPCR) testing was done on both fecal and saliva (1468 samples) from 734 children < 5 months old living in the Amazon (Brazil, Guyana, and Venezuela). High and median HBoV viral load samples were used for extraction, nested PCR amplification, and sequencing for genotyping. HBoV mRNA detection was done by reverse transcription following DNA amplification. RESULTS: The overall HBoV frequencies were 14.2% (69/485; AGE) and 14.1% (35/249; ARI) (p = 0.83). HBoV exclusively infected 4.5% (22/485; AGE) and 4% (10/249) of the Amazonian children (Odds ratios 1.13, 95% confidence interval= 2.42-0.52). HBoV 1 was mainly detected in feces and saliva from AGE children; and HBoV2, from ARI children. HBoV mRNA was detected only in feces. The Rotarix™ vaccination status did not affect the HBoV frequencies. CONCLUSIONS: We suggest that, after entry into the air/oral pathways, HBoV1 continues infecting toward the intestinal tract causing AGE. HBoV2 can be a causative agent of AGE and ARI in younger Amazonian children.

Norovirus infection and HBGA host genetic susceptibility in a birth community-cohort, Rio de Janeiro, Brazil.

Norovirus has emerged as an important viral agent of acute pediatric gastroenteritis, with a growing genetic diversity reported in the last decades. Histo-blood group antigens (HBGAs) present on the surface of enterocytes are susceptibility factors for norovirus infection and differ between populations which could affects the epidemiology and evolution of these viruses. This study investigated the frequency, incidence and genetic diversity of noroviruses in a cohort of rotavirus A vaccinated children in association to the host HBGA (Secretor/Lewis) genetic susceptibility profile. Norovirus genogroups I and II (GI/GII) were screened by RT-qPCR in 569 stool samples from 132 children followed-up from birth to 11 months of age during 2014--2018. Noroviruses were identified in 21.2% of children enrolled in this study, with a norovirus detection rate of 5.6% (32/569), in 17.1% and 4.7% of acute diarrheic episodes (ADE) and non-ADE, respectively. The norovirus incidence was 5.8 infections per 100 child-months. Partial nucleotide sequencing characterized six different norovirus genotypes, with GII.4 Sydney 2012 being detected in 50% associated with three different polymerase genotypes (GII·P31, GII·P16 and GII·P4 New Orleans 2009). FUT3 genotyping was yielded seven new mutations in this population. A significant association between symptomatic norovirus infection and secretor profile could be inferred.

Antiviral activity of 4-oxoquinoline-3-carboxamide derivatives against bovine herpesvirus type 5.

BACKGROUND: Bovine herpesvirus type 5 is an important agent of meningoencephalitis in cattle and has been identified in outbreaks of bovine neurological disease in several Brazilian states. In recent years, oxoquinoline derivatives have become an important focus in antiviral drug research. METHODS: The cytotoxicity and anti BoHV-5RJ42/01 activity of a set of synthetic 4-oxoquinoline derivatives 4a-k were assayed on Madin-Darby Bovine Kidney cell and antiviral activity by plaque reduction assay. RESULTS: The most promising substance (4h) exhibited CC50 and EC50 values of 1,239 µM ±5.5 and 6.0 µM ±1.5, respectively, with an SI =206. Two other compounds 4j (CC50 = 35 µM ±2 and EC50 = 24 µM ±7.0) and 4k (CC50= 55 µM ±2 and EC50 = 24 µM ±5.1) presented similar inhibitory profile and selectivity indexes of 1.4 and 2.9, respectively. The results of the time-of-addition studies revealed expressive reduction of virus production (≥80%) in different stages of virus replication cycle except for compound 4h that slightly inhibited virus yield in the first 2 h post infection, but it showed expressive virus inhibition after this time. CONCLUSIONS: All three compounds slightly interact with the virus on the virucidal assay and they are not able to block virus attachment and penetration. Antiviral effect of oxoquinoline 4h was more prominent than acyclovir which leads us to suggest compound 4h as a promising molecule for further anti-BoHV-5 drug design.