NS1 Antibodies Research Articles

Retrospective study on the dengue fever outbreak in Puntland State, Somalia

BackgroundDengue infection is a mosquito-borne, endemic viral disease, particularly in developing countries. Here, we report the results of the clinicodemographic, serologic profile and the monthly occurrence of a recent dengue fever outbreak in Puntland State (Somalia).MethodologyWe analyzed the data of 956 dengue-suspected patients who were investigated using the rapid diagnostic testing (RDT) method for detecting NS1 (dengue virus non-structural protein) and IgM antibodies employing the SD Biosensor Dengue Dou NS Ag and IgM test kit (Germany) at the Puntland Public Health Referral Laboratory from November 21, 2022, to May 27, 2023.ResultsWe found that 118 cases were positive for dengue among the suspected patients enrolled in the present study. Of these cases, 76.2% were dengue NSI positive, 13.6% were dengue IgM positive, and 10.2% were both NSI and IgM positive. The number of females and males in the confirmed cases was equal, and most (48.3%) were aged 20 years or less. 43.1% of them lived in the Nugal region, particularly in Garowe. Clinically, fever was the most frequent symptom (88.9%). The cases peaked in December 2022 but dropped from January to March, with a slight rise in February, and then increased in April and May 2023.ConclusionThis study highlights the clinicodemographic characteristics, seroprevalence, and monthly occurrence of dengue in Puntland. We recommend improving vector control measures, enhancing case management, strengthening dengue surveillance, developing an early warning system, and conducting future studies to characterize the circulating strains.

Dengue NS1 antibodies are associated with clearance of viral NS1.

Dengue vascular permeability syndrome is the primary cause of death in severe dengue infections. The protective versus potentially pathogenic role of dengue NS1 antibodies are not well understood. The main goal of this analysis was to characterize the relationship between free NS1 concentration and NS1 antibody titers in primary and secondary dengue infection in order to better understand the presence and duration of NS1 antibody complexes in clinical dengue infections. Hospitalized participants with acute dengue infection were recruited from Northern Colombia between 2018 to 2020. Symptom assessment including dengue signs and symptoms, chart review and blood collection was performed. Primary versus secondary Dengue was assessed serologically. NS1 titers and anti-NS1 antibodies were measured daily. Patients with secondary infection have higher antibody titers than those in primary infection, and we find a negative correlation between anti-NS1 antibody titer and NS1 protein. We demonstrate that in a subset of secondary infection, there are indeed NS1 antibody-antigen complexes at the admission day during the febrile phase that are not detectable by the recovery phase. Furthermore, dengue infection status is associated with higher circulating sialidases. The negative correlation between antibody and protein suggests that antibodies may play a role in clearing this viral protein.

First DFT-supported point of care and novel electrochemical biosensing: Determination of yellow fever NS1 antibody in human plasma

In our study, we developed a point of care electrochemical biosensing platform based on the functionalized cysteine-positioned gold electrode to diagnose yellow fever disease from human plasma samples. The developed platform underwent characterization through diverse methods encompassing cyclic voltammetry, electrochemical impedance spectroscopy, scanning electron microscopy, energy dispersive X-ray spectroscopy, and density-functional theory. The capacitive interaction between yellow fever virus non-structural antigen and antibody gave a cathodic signal at approximately −260 mV, and increased in proportion to the amount of non-structural antibody. The created electrochemical biosensor has an ability to detect 96 ag/mL of the yellow fever non-structural antibody with an extensive analytical range varied from 0.1 fg/mL to 1 μg/mL. The interference effects of various substances that could be found in human plasma, and the performance of the method were examined from the point of recovery and relative standard deviation for human plasma samples; hereby, the results confirmed the unprecedented selectivity and accuracy of the proposed method.

IJCM_299A: Clinical profile of patients with dengue: a cross-sectional study from a tertiary care hospital, Karnataka

Background: Dengue fever (DF) are among the most important mosquito- borne diseases of the Indian subcontinent and have become a major global public health concern. Its clinical manifestations of which vary from influenza- like illness (DF) to life-threatening dengue hemorrhagic fever (DHF)/dengue shock syndrome (DSS). The purpose of the study was to find out the mode of presentation, biochemical profile and complications of Dengue cases in an apical level. Objectives: 1. To identify socio-demographic characteristics and clinical features; 2. To document the disease specific management and outcomes Methodology: A cross-sectional study of admitted patients was conducted in the department of medicine and Infectious Diseases over a period of 9 months (15/2/2023 -15/11/2023). Patients aged above 18 years with serology proven (nonstructural protein 1 [NS1]/dengue immunoglobulin M [IgM]) DF were included in this study. Their Socio demographic Details, clinical and laboratory data was recorded and analyzed. Results: Preliminary Results: Out of 125 cases, - 89 (71.2 %) patients were males and 36 (28.8%) were females. - The most common presentations were fever (96%) followed by Nausea/vomiting (40%), Headache (35%) and myalgia (31%). - Dengue NS1 and IgM antibodies were positive in 87.3% and 88.12% of the patients, respectively. - the incidence of DF, DHF, and DSS was 87.2, 11.2, and 1.6% respectively. - Shock, bleeding, and elevated serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase levels predicted adverse outcome. Conclusion: DF can present with a spectrum of clinical manifestations ranging from mild self-limiting illness to severe fatal disease. It can have varied and multi-systemic manifestations which can go unrecognized. Continuous seroepidemiological surveillance is essential to control outbreak and minimize morbidity and mortality.

Urinary dengue NS1 detection on Au-decorated ZnO nanowire platform

Biodetection for non-invasive diagnostics of fluids, especially urine, remains a challenge to scientists due to low target concentrations. And biological complexes of the detection target may contain contaminants that also interfere with any assay. Dengue non-structural 1 protein (Dengue NS1) is an important biomarker for dengue hemorrhagic fever and dengue shock syndrome. Here, we developed an Au-decorated nanowire platform and applied it with a sandwich fluorophore-linked immunosorbent well plate assay (FLISA) to detect Dengue NS1 in urine. For the platform, we fabricated zinc oxide (ZnO) nanowires to provide a high surface area and then coated them with gold nanoparticles (ZnO/Au nanowires) to simply modify the Dengue NS1 antibody and enhance the fluorescence intensity. Our platform employs a sandwich FLISA that exhibits high sensitivity, specifically detecting Dengue NS1 with a limit of detection (LOD) of 1.35 pg/mL. This LOD was 4500-fold lower than the LOD of a commercially available kit for Dengue NS1 enzyme-linked immunosorbent assay. We believe that our ZnO/Au nanowire platform has the potential to revolutionize the field of non-invasive diagnostics for dengue.

Tick-borne encephalitis virus IgG antibody surveillance: vaccination- and infection-induced seroprevalences, south-western Germany, 2021.

BackgroundThe exact epidemiology of tick-borne encephalitis virus (TBEV) infections is unknown because many TBEV infections have an influenza-like or asymptomatic course. Surveillance data are based on patients with any (predominantly neurological) symptoms that prompted diagnostic testing. Infection- and vaccine-induced antibodies against TBEV can be distinguished using an NS1IgG ELISA.AimIn a seroprevalence study we aimed to investigate TBEV antibody prevalence, incidences, manifestation indices and potential protection rates in a highly endemic district in south-western Germany.MethodsWe analysed 2,220 samples from healthy blood donors collected between May and September 2021. The reported number of TBEV infections was provided on a sub-district level by the local public health authorities. Blood samples were first screened using a TBEVIgG ELISA. In a second step, all positive samples were further analysed with a recently established NS1IgG ELISA. The presence of specific antibodies against TBEV (excluding cross-reacting antibodies against other flaviviruses) was confirmed by testing screening-positive samples with a microneutralisation assay.ResultsOf 2,220 included samples, 1,257 (57%) tested positive by TBEVIgG ELISA and 125 tested positive for infection-induced TBEV NS1 antibodies, resulting in a TBEV NS1IgG seroprevalence at 5.6% in our population. The yearly incidence based on the NS1 ELISA findings resulted in 283 cases per 100,000 inhabitants.ConclusionUsing the TBEV NS1IgG assay, we confirmed a manifestation index of ca 2% and a high incidence of predominantly silent TBEV infections (> 250/100,000/year), which exceeds the incidence of notified cases (4.7/100,000/year) considerably.

Hepatocellular Damage in the Patients presenting with Dengue Fever

Background: Dengue fever is becoming endemic in Pakistan as shown by its increasing prevalence in the summer seasons for almost the last decade. Elevation of liver enzymes indicating underlying liver damage, is a common phenomenon and may be associated with other complications. Objective: To find out the frequency of hepatocellular damage in the patients presenting with dengue fever as evident by elevated liver enzymes.Material and Methods: This was a descriptive study performed in the medical unit of Hayatabad Medical Complex Peshawar Pakistan. Patients were consecutively collected from the wards, outpatients, and emergency department. The patient's collection was from the year 2022 epidemic from 10th Jul to 23rd Oct. Patients with consistent clinical features, were diagnosed on the bases of dengue NS1 test and antibodies titers. Liver enzymes, complete blood counts and ultrasound were performed to find out any evidence of liver damage and plasma leaks as evident by pleural effusion or ascites. Alanine aminotransferase (ALT) of more than 50 U/L was considered as elevated in our study. Patients with elevated liver enzymes due to expected reasons other than dengue fever as per clinical records, were excluded from the study. The patient's data was noted on a preformed Performa for further analysis. Results: We consecutively collected 500 patients for the study. The number of male patients was 59% (n=295) while female patients were 41% (n=205). The age range was 15 to 75 years (mean 45, SD 21.32). The overall frequency of elevated (ALT) was 68.2% (n=341). Stratification of patients according to the ALT level shows that only 13.68% were having an ALT level of more than 300 U/L. The frequency was 45.45% in patients without complications, 91.60% in patients with warning signs, 85.71% in severe dengue and 100% with acute liver failure. Patients with an alanine aminotransferase (ALT) of =>300U/L were having a hospital stay of 5 to 12 days (mean 8.81, SD 2.6) days verses 4 to 9 days (mean 5.8, SD 1.9) in the patients having <300U/LConclusion: Most of the patients with dengue fever have elevated alanine aminotransferase level indicative of underlying hepatocellular damage. Such patients usually recover without any serious consequences except those having elevation of 300U/l or more whose hospital stay was prolonged, and a smaller percentage was associated with acute liver failure.Keywords: dengue fever, dengue NS1, hepatocellular damage, liver enzymes, hospital stay.

Dengue fever ophthalmic manifestations: A review and update.

Dengue fever, the most common arbovirus disease, affects an estimated 390 million people annually. Dengue virus (DENV) is an RNA virus of the Flaviviridae family with four different serotypes. Dengue haemorrhagic fever is the deadliest form of dengue infection and is characterised by thrombocytopaenia, hypotension, and the possibility of multi-system organ failure. The mechanism hypothesised for DENV viral replication is intrinsic antibody-dependent enhancement, which refers to Fcγ receptor-mediated viral amplification. This hypothesis suggests that the internalisation of DENV through the Fcγ receptor inhibits antiviral genes by suppressing type-1 interferon-mediated antiviral responses. DENV NS1 antibodies can promote the release of various inflammatory mediators in the nuclear transcription factor pathway (NF-κB-dependent), including monocyte chemoattractant protein (MCP)-1, interleukin (IL)-6, and IL-8. As a result, MCP-1 increases ICAM-1 expression and facilitates leukocyte transmigration. In addition, anti-DENV NS1 antibodies induce endothelial cell apoptosis via a nitric oxide-regulated pathway. A chain reaction involving pre-existing DENV heterotypic antibodies and innate immune cells causes dysfunction in complement system activity and contributes to the action of autoantibodies and anti-endothelial cells, resulting in endothelial cell dysfunction, blood-retinal barrier breakdown, haemorrhage, and plasma leakage. A spectrum of ocular diseases associated with DENV infection, ranging from haemorrhagic to inflammatory manifestations, has been reported in the literature. Although rare, ophthalmic manifestations can occur in both the anterior and posterior segments and are usually associated with thrombocytopenia. The most common ocular complication is haemorrhage. However, ophthalmic complications, such as anterior uveitis and vasculitis, suggest an immune-mediated pathogenesis.

268. Dengue - SARS-CoV-2 co-infection: Experience in hospitalized patients during COVID-19 pandemic

Abstract Background Dengue fever and COVID-19 co-infection constitute a significant public health concern in Latin America, becoming a clinical challenge to distinguish these two entities in early stages of the disease. Clinical outcomes of coinfected hospitalized patients have not been well established. Methods A cross-sectional study was conducted. We included suspected patients diagnosed with COVID-19/dengue co-infection admitted at Hospital Fundación Valle del Lili, Cali – Colombia, from March 2020 to March 2021. All dengue patients had positive NS1 and/or IgM dengue antibodies. SARS-CoV-2 infection was confirmed by RT-PCR or antigen rapid test from nasopharyngeal swab. Laboratory and clinical data were recollected from the clinical laboratory database, clinical charts, and institutional COVID-19 registry. Results A total of 90 COVID-19 patients were included. 72 patients were confirmed only with COVID-19, and 18 with dengue co-infection. Most patients were male: 46 (63.9%) vs. 13 (72.2%). None of these study patients were vaccinated against COVID-19 or dengue. The median time from symptoms onset and the diagnosis was five days, and fever was the most common symptom for both groups. There were significant differences between COVID-19 patients and coinfected patients regarding presence of dyspnea (22.2% vs. 61.1%; p=0.003), desaturation (13.4% vs. 53.3%; p=0.002) and a higher neutrophil/lymphocyte ratio (NLR) (3.84 vs. 5.59; p = 0.038). The co-infection was associated with a worse presentation of the COVID-19 infection (p=0.002), an increased requirement of initial supplemental oxygen therapy (p=0.007), mechanical ventilation (p=0.0004), ICU management at the admission (p=0.002), and ICU final management (p=0.002). Overall mortality in patients with co-infection was 44.4% vs. 6.9% in only COVID-19 infected patients (p< 0.001). Conclusion Despite the pandemic era, the possibility of co-infection of these two entities must be considered. Admitted coinfected patients were associated with worse clinical outcomes and higher mortality. According to our results, patients with co-infection present with severe respiratory symptoms and an elevated NLR. The impact of the Covid 19 vaccination on this coinfection is unknown. Disclosures Olga Agudelo, n/a, Fundación valle del lili: Board Member.

Look Out for Fever: Clinical Profile of Dengue in Young Adults in a Tertiary Care Center in North India.

Background Dengue fever (DF) is a common viral disease, clinical manifestations of which vary from influenza-like illness (DF) to life-threatening dengue hemorrhagic fever (DHF)/dengue shock syndrome (DSS). The aim of this article was to study the clinical profile of DF in young adults. Material and Methods This was an observational study conducted in the department of medicine over a period of 2 years (January 1, 2013-December 31, 2014). Patients aged between 18 and 30 years with serology proven (nonstructural protein 1 [NS1]/dengue immunoglobulin M [IgM]) DF were included in this study. The clinical and laboratory data was recorded and analyzed. Results Out of 418 cases, the incidence of DF, DHF, and DSS was 87.32, 7.66, and 5.02%, respectively. The most common presentations were fever (99.76%) followed by vomiting (29.43%), pain abdomen (17.94%), myalgias (13.16%), petechial rash (12.92%), and bleeding (10.29%). Dengue NS1 and IgM antibodies were positive in 87.3% and 88.12% of the patients, respectively. Ascites, splenomegaly, hepatomegaly, pleural effusion, gall bladder wall edema, and pericardial effusion were present in 8.13, 6.94, 6.70, 5.98, 2.63, and 0.72% of the patients, respectively. Complications included bleeding (10.29%), acute respiratory distress syndrome (1.67%), myocarditis (1.44%), seizures (1.44%), hemarthrosis (0.24%), and encephalopathy (0.24%). The mortality rate was 3.35% with death of 14 patients. Shock, bleeding, and elevated serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase levels predicted adverse outcome. Conclusion DF can present with a plethora of clinical manifestations in endemic areas. Adverse outcome is more likely if patients have elevated SGOT levels, shock, and bleeding. Continuous seroepidemiological surveillance is essential to control outbreak and minimize morbidity and mortality.

Epidemiological and hematological investigation of dengue virus infection.

Dengue is a mosquito-borne viral illness that infects humans. For the past few decades, it has been declared a global public health problem. The current study, conducted at the district headquarter hospital (DHQ) Bannu between June to September 2018, was based on the seroprevalence of antibodies against dengue virus serotypes and their hematological parameters among the patients. A total of 1738 individuals suspected of having dengue were diagnosed through NS1, IgG, and IgM antibodies and RT-PCR techniques. Of all the samples, 716 (41.19%) were found to be positive for dengue. A higher infection rate was found in males (65.92%) compared with females (34.07%). The most affected age group was 16-40 years, whereas the most affected tehsil was Bannu, where the DENV-3 serotype was prevalent. The rare serotype (DENV-4) was found in 1% of cases. Symptoms including fever (100%), myalgia (100%), headache (61.31%), vomiting (34.63%), and rashes were common among the dengue patients. However, the mild cases showed fewer clinical signs compared with the severely infected cases. The study also revealed a significant association (P < 0.05) between hematological parameters and dengue infection, showing a significant decrease in TC, eosinophils, neutrophils, and platelets and a significant increase in monocytes and lymphocytes. Based on the current report, it is concluded that patients with the above symptoms and hematological changes may have an increased probability of dengue and should be kept under observation to separate dengue-positive patients and to enhance the treatment process.

Measles-based Zika vaccine induces long-term immunity and requires NS1 antibodies to protect the female reproductive tract

Zika virus (ZIKV) can cause devastating effects in the unborn fetus of pregnant women. To develop a candidate vaccine that can protect human fetuses, we generated a panel of live measles vaccine (MV) vectors expressing ZIKV-E and -NS1. Our MV-based ZIKV-E vaccine, MV-E2, protected mice from the non-lethal Zika Asian strain (PRVABC59) and the lethal African strain (MR766) challenge. Despite 100% survival of the MV-E2 mice, however, complete viral clearance was not achieved in the brain and reproductive tract of the lethally challenged mice. We then tested MV-based vaccines that expressed E and NS1 together or separately in two different vaccines. We observed complete clearance of ZIKV from the female reproductive tract and complete fetal protection in the lethal African challenge model in animals that received the dual antigen vaccines. Additionally, MV-E2 and MV-NS1, when administered together, induced durable plasma cell responses. Our findings suggest that NS1 antibodies are required to enhance the protection of ZIKV-E antibodies in the female reproductive tract.

Impedimetric immunosensor for the NS1 dengue biomarker based on the gold nanorod decorated graphitic carbon nitride modified electrode

Dengue has been a threatening vector-borne viral disease across different countries of the world. NS1 is a non-structural dengue biomarker that is released into the bloodstream during the initial stages of the infection and is used in the early diagnosis of the disease. In this work, we present a high-performance NS1 immunosensor based on gold nanorod decorated graphitic carbon nitride (AuNRs-g-C3N4) modified glassy carbon electrodes (GCE). AuNRs-g-C3N4 composite is synthesized, which possesses excellent electro-activity, fast electron transfer kinetics, and high catalytic property. NS1 antibody is immobilized onto the surface of the AuNRs-g-C3N4 modified GCE and used as an impedimetric sensing probe for the quantitative sensing of NS1 antigen through electrochemical impedance spectroscopy. We have chosen [Fe (CN)6]3−/4− as a redox couple to observe the respective changes in charge transfer resistance (Rct) associated with antigen bonding with an antibody both in PBS buffer as well as in human serum. The prepared immunosensor shows an excellent electrocatalytic response for the quantitative determination of NS1. The analytical parameters obtained by using this immunosensor are found comparable or better to previously reported NS1 sensors and open new insights with great potential for the application of point of care besides application in the diagnosis of Dengue.

Enhanced Seroconversion to West Nile Virus Proteins in Mice by West Nile Kunjin Replicon Virus-like Particles Expressing Glycoproteins from Crimean-Congo Hemorrhagic Fever Virus.

Removal of genes coding for major parts of capsid (C), premembrane (prM), and envelope (E) proteins on the flavivirus genome aborts the production of infectious virus particles where the remaining genome forms a replicon that retains replicability in host cells. The C-prM-E proteins can also be expressed in trans with the flavivirus replicons to generate single-round infectious replicon virus-like particles (RVPs). In this study, we characterized the use of RVPs based on the Kunjin strain of WNV (WNVKUN) as a putative WNV vaccine candidate. In addition, the WNVKUN C-prM-E genes were substituted with the Crimean–Congo hemorrhagic fever virus (CCHFV) genes encoding the glycoproteins Gn and Gc to generate a WNVKUN replicon expressing the CCHFV proteins. To generate RVPs, the WNVKUN replicon was transfected into a cell line expressing the WNVKUN C-prM-E. Using immunoblotting and immunofluorescence assays, we showed that the replicon can express the CCHFV Gn and Gc proteins and the RVPs can transduce cells to express WNVKUN proteins and the CCHFV Gn and Gc proteins. Our study also revealed that these RVPs have potential as a vaccine platform with low risk of recombination as it infects cells only in one cycle. The immunization of mice with the RVPs resulted in high seroconversion to both WNV E and NS1 but limited seroconversion to CCHFV Gn and Gc proteins. Interestingly, we found that there was enhanced production of WNV E, NS1 antibodies, and neutralizing antibodies by the inclusion of CCHFV Gc and Gn into WNVKUN RVPs. Thus, this study indicates a complementary effect of the CCHFV Gn and Gc proteins on the immunogenicity by WNVKUN RVPs, which may be applied to develop a future vaccine against the WNV.

Development and evaluation of NS1 protein based i-ELISA for serodiagnosis of Bluetongue disease

Bluetongue (BT) is an important viral disease of small ruminants and causes major economic losses in India. For serodiagnosis of BT, recombinant antigen-based assays are considered as alternatives to conventional approaches such as serum neutralization test. The present study aimed at the development of an indirect- enzyme-linked immunosorbent assay (i-ELISA) using bluetongue (BTV) recombinant NS1. NS1 gene of BTV encoding a mature NS1 protein was produced as a recombinant protein (rNS1) in Escherichia coli. The immunogenic potential of purified rNS1 was confirmed by detecting specific NS1 antibody responses in sera collected from immunized sheep using ELISA. An i-ELISA based on rNS1 was developed and optimized. In comparison to a commercially available c-ELISA kit, in the detection of BTV specific antibodies, this new assay exhibited a diagnostic sensitivity of 91.2%. This study highlighted the potential utility of rNS1 protein as a safe and novel diagnostic reagent in comparison to live virus antigen, in the development of serodiagnostic assay for surveillance of BTV infection in sheep and goats.

Pathogenesis of Dengue virus in Host immune system and its genomic variation

Dengue viruses are the most prevalent arthropod-borne viral diseases in humans, infecting 50-100 million people each year. Its serotypes are the most common causes of arboviral illness, putting half of the world's population at risk of infection. Because there is no vaccine or antiviral medicines, the only way to manage the disease is to reduce the Aedes mosquito vectors. DENV infection can be asymptomatic or cause a self-limiting, acute febrile illness with varying degrees of severity. High fever, headache, stomach discomfort, rash, myalgia, and arthralgia are the typical symptoms of dengue fever (DF). Thrombocytopenia, vascular leakage, and hypotension are symptoms of severe dengue, dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS). Systemic shock characterizes DSS, which can be deadly. Dengue virus infection pathogenesis is linked to a complex interaction between virus, host genes, and host immune response. Major drivers of disease vulnerability include host factors such as antibody-dependent enhancement (ADE), memory cross-reactive T cells, anti-DENV NS1 antibodies, autoimmunity, and genetic variables. The NS1 protein and anti-DENV NS1 antibodies were thought to be involved in the development of severe dengue. The progressive infection may change the cytokine response of cross reactive CD4+ T cells. The need for dengue vaccines that can generate strong protective immunity against all four serotypes is required. To create such vaccines, a thorough understanding of DENV adaptive immunity is required. Structural and functional research have shown that the degree of prM protein cleavage as well as the ensemble of conformational states sampled by virions influence DENV sensitivity to antibody-mediated neutralization, which has crucial implications for vaccine formulation.

Nuclear-localized human respiratory syncytial virus NS1 protein modulates host gene transcription.

SUMMARYHuman respiratory syncytial virus (RSV) is a common cause of lower respiratory tract infections in the pediatric, elderly, and immunocompromised individuals. RSV non-structural protein NS1 is a known cytosolic immune antagonist, but how NS1 modulates host responses remains poorly defined. Here, we observe NS1 partitioning into the nucleus of RSV-infected cells, including the human airway epithelium. Nuclear NS1 coimmunoprecipitates with Mediator complex and is chromatin associated. Chromatin-immunoprecipitation demonstrates enrichment of NS1 that overlaps Mediator and transcription factor binding within the promoters and enhancers of differentially expressed genes during RSV infection. Mutation of the NS1 C-terminal helix reduces NS1 impact on host gene expression. These data suggest that nuclear NS1 alters host responses to RSV infection by binding at regulatory elements of immune response genes and modulating host gene transcription. Our study identifies another layer of regulation by virally encoded proteins that shapes host response and impacts immunity to RSV.

The relationship between platelet count and the onset of leaking phase in dengue patients

Introduction: The complications of dengue are related to reduced intravascular volume following plasma leakage. Thrombocytopenia or platelet dysfunctions are detected in all stages of the illness and are related to the clinical outcome. The main objective of the study was to correlate absolute platelet count to the onset of leaking phase in dengue patients who had entered into leaking phase after the hospital admission. Methods: One hundred and sixteen patients (age range 14-74 years, median age 33 years) who entered the leaking phase after admission were recruited to the study. Dengue infection in patients was confirmed with either the presence of positive NS1 or positive IgM antibodies. Serial ultrasonography was done from admission until the leaking phase is detected. Platelet counts were assessed twice per day just prior to the ultrasonography. Results: There were 47 (40.5%) females and 69 (59.5%) males among the recruited patients. The mean number of days at which leaking was detected following onset of fever was 4.9 ± 0.9 days. The mean platelet count at the onset of leaking phase was 30,051 ± 17,023 /μL. Age and the platelet count at the time of onset of leaking phase was significantly negatively correlated (whole group r = -0.323 p &lt; 0.001; in females r = -0.369, p = 0.011; males r = -0.280 p = 0.020). Platelet count at the time of onset of leaking phase was significantly lower in the patients older than 30 years of age (27,577.5 ± 17,361.4) compared to those of the patients younger than 30 years (33,955.6 ± 15,888.8) (p=0.032). Upper limit of the range of platelet count at the onset of leaking phase was 77, 000/ μL which was slightly lower in females. Conclusions: According to this study, the value of platelet count as a predictor of the progression of dengue infection depends on the age of the patients. Young patients are more prone to develop leaking phase with higher platelet counts than the older patients.

Non-primate hepacivirus transmission and prevalence: Novel findings of virus circulation in horses and dogs in Morocco.

Non-primate hepacivirus (NPHV) is a homolog of hepatitis C virus and has been isolated from dogs and horses. Data on NPHV prevalence and distribution are not complete, and there is a particular lack of reports from the African continent. The present study represents the first investigation of NPHV prevalence in horses and dogs in North Africa. Blood was collected from 172 horses and 36 dogs at different locations in Morocco, and screened for NPHV RNA using nested PCR targeting 5'UTR and NS3 regions and analyzed for anti-NPHV NS3 antibody using a Gaussia luciferase immunoprecipitation system-to determine seroprevalence. Eight sequences of the NS3 region isolated from positive serum samples were targeted for phylogenetic analysis. Horses and dogs showed respective NPHV RNA positivity rates of 10.5% and 5.5%, and seroprevalences of 65.7% and 8.33%. Juvenile horses appeared more susceptible to infection, with a 23.5% NHPV RNA positivity rate. Seropositivity was more extensive in mares than stallions (77.14% vs. 46.27%, p<0.0001). Phylogenetically, that NPHV NS3 genes isolated from horses and dog are clustered together. The NPHV strains we detected showed no correlation with geographic location within Morocco. In conclusion, Moroccan horses showed much evidence of previous and/or current NPHV infection, with young age and female sex as noted potential risk factors. Interestingly, NPHV is circulating in dogs as well as horses, suggesting that it has crossed species barriers and that horses and dogs are potential vectors by which an ancestor to hepatitis C virus was transmitted into human populations.

A dark side to NS1 antibodies?

The NS1 protein of flaviviruses is taking center stage. Recent work has made it an attractive target for development of vaccines and immunotherapeutics. Cavazzoni and colleagues (2021. J. Exp. Med.https://doi.org/10.1084/jem.20210580) now reveal a dark side to NS1, linking it to the development of self-reactive antibodies.