Characterization of Two Highly Specific Monoclonal Antibodies Targeting the Glycan Loop of the Zika Virus Envelope Protein.

Zika virus (ZIKV) is an emerging flavivirus associated with several neurological diseases such as Guillain-Barré syndrome in adults and microcephaly in newborn children. Its distribution and mode of transmission (via Aedes aegypti and Aedes albopictus mosquitoes) collectively cause ZIKV to be a serious concern for global health. High genetic homology of flaviviruses and shared ecology is a hurdle for accurate detection. Distinguishing infections caused by different viruses based on serological recognition can be misleading as many anti-flavivirus monoclonal antibodies (mAbs) discovered to date are highly cross-reactive, especially those against the envelope (E) protein. To provide more specific research tools, we produced ZIKV E directed hybridoma cell lines and characterized two highly ZIKV-specific mAb clones (mAbs A11 and A42) against several members of the Flavivirus genus. Epitope mapping of mAb A11 revealed glycan loop specificity in Domain I of the ZIKV E protein. The development of two highly specific mAbs targeting the surface fusion protein of ZIKV presents a significant advancement in research capabilities as these can be employed as essential tools to enhance our understanding of ZIKV identification on infected cells ex vivo or in culture.

Detection of anti-premembrane antibody as a specific marker of four flavivirus serocomplexes and its application to serosurveillance in endemic regions.

In the past few decades, several emerging/re-emerging mosquito-borne flaviviruses have resulted in disease outbreaks of public health concern in the tropics and subtropics. Due to cross-reactivities of antibodies recognizing the envelope protein of different flaviviruses, serosurveillance remains a challenge. Previously we reported that anti-premembrane (prM) antibody can discriminate between three flavivirus infections by Western blot analysis. In this study, we aimed to develop a serological assay that can discriminate infection or exposure with flaviviruses from four serocomplexes, including dengue (DENV), Zika (ZIKV), West Nile (WNV) and yellow fever (YFV) viruses, and explore its application for serosurveillance in flavivirus-endemic countries. We employed Western blot analysis including antigens of six flaviviruses (DENV1, 2 and 4, WNV, ZIKV and YFV) from four serocomplexes. We tested serum samples from YF-17D vaccinees, and from DENV, ZIKV and WNV panels that had been confirmed by RT-PCR or by neutralization assays. The overall sensitivity/specificity of anti-prM antibodies for DENV, ZIKV, WNV, and YFV infections/exposure were 91.7%/96.4%, 91.7%/99.2%, 88.9%/98.3%, and 91.3%/92.5%, respectively. When testing 48 samples from Brazil, we identified multiple flavivirus infections/exposure including DENV and ZIKV, DENV and YFV, and DENV, ZIKV and YFV. When testing 50 samples from the Philippines, we detected DENV, ZIKV, and DENV and ZIKV infections with a ZIKV seroprevalence rate of 10%, which was consistent with reports of low-level circulation of ZIKV in Asia. Together, these findings suggest that anti-prM antibody is a flavivirus serocomplex-specific marker and can be employed to delineate four flavivirus infections/exposure in regions where multiple flaviviruses co-circulate.

Identification of the flavivirus conserved residues in the envelope protein hinge region for the rational design of a candidate West Nile live-attenuated vaccine.

The flavivirus envelope protein is a class II fusion protein that drives flavivirus-cell membrane fusion. The membrane fusion process is triggered by the conformational change of the E protein from dimer in the virion to trimer, which involves the rearrangement of three domains, EDI, EDII, and EDIII. The movement between EDI and EDII initiates the formation of the E protein trimer. The EDI-EDII hinge region utilizes four motifs to exert the hinge effect at the interdomain region and is crucial for the membrane fusion activity of the E protein. Using West Nile virus (WNV) NY99 strain derived from an infectious clone, we investigated the role of eight flavivirus-conserved hydrophobic residues in the EDI-EDII hinge region in the conformational change of E protein from dimer to trimer and viral entry. Single mutations of the E-A54, E-I130, E-I135, E-I196, and E-Y201 residues affected infectivity. Importantly, the E-A54I and E-Y201P mutations fully attenuated the mouse neuroinvasive phenotype of WNV. The results suggest that multiple flavivirus-conserved hydrophobic residues in the EDI-EDII hinge region play a critical role in the structure-function of the E protein and some contribute to the virulence phenotype of flaviviruses as demonstrated by the attenuation of the mouse neuroinvasive phenotype of WNV. Thus, as a proof of concept, residues in the EDI-EDII hinge region are proposed targets to engineer attenuating mutations for inclusion in the rational design of candidate live-attenuated flavivirus vaccines.

Detection of anti-premembrane antibody as a specific marker of four flavivirus serocomplexes and its application to serosurveillance in endemic regions.

In the past few decades, several emerging/re-emerging mosquito-borne flaviviruses have resulted in disease outbreaks of public health concern in the tropics and subtropics. Due to cross-reactivities of antibodies recognizing the envelope protein of different flaviviruses, serosurveillance remains a challenge. Previously we reported that anti-premembrane (prM) antibody can discriminate between three flavivirus infections by Western blot analysis. In this study, we aimed to develop a serological assay that can discriminate infection or exposure with flaviviruses from four serocomplexes, including dengue (DENV), Zika (ZIKV), West Nile (WNV) and yellow fever (YFV) viruses, and explore its application for serosurveillance in flavivirus-endemic countries. We employed Western blot analysis including antigens of six flaviviruses (DENV1, 2 and 4, WNV, ZIKV and YFV) from four serocomplexes. We tested serum samples from YF-17D vaccinees, and from DENV, ZIKV and WNV panels that had been confirmed by RT-PCR or by neutralization assays. The overall sensitivity/specificity of anti-prM antibodies for DENV, ZIKV, WNV, and YFV infections/exposure were 91.7%/96.4%, 91.7%/99.2%, 88.9%/98.3%, and 91.3%/92.5%, respectively. When testing 48 samples from Brazil, we identified multiple flavivirus infections/exposure including DENV and ZIKV, DENV and YFV, and DENV, ZIKV and YFV. When testing 50 samples from the Philippines, we detected DENV, ZIKV, and DENV and ZIKV infections with a ZIKV seroprevalence rate of 10%, which was consistent with reports of low-level circulation of ZIKV in Asia. Together, these findings suggest that anti-prM antibody is a flavivirus serocomplex-specific marker and can be employed to delineate four flavivirus infections/exposure in regions where multiple flaviviruses co-circulate.

Infection of Feral Phenotype Swine with Japanese Encephalitis Virus.

Background: Japanese encephalitis virus (JEV) is a mosquito-borne zoonotic flavivirus and the leading cause of pediatric encephalitis in the Asian Pacific region. The transmission cycle primarily involves Culex spp. mosquitoes and Ardeid birds, with domestic pigs (Sus scrofa domestica) being the source of infectious viruses for the spillover of JEV from the natural endemic transmission cycle into the human population. Although many studies have concluded that domestic pigs play an important role in the transmission cycle of JEV, and infection of humans, the role of feral pigs in the transmission of JEV remains unclear. Since domestic and feral pigs are the same species, and because feral pig populations in the United States are increasing and expanding geographically, the current study aimed to test the hypothesis that if JEV were introduced into the United States, feral pigs might play a role in the transmission cycle. Materials and Methods: Sinclair miniature pigs, that exhibit the feral phenotype, were intradermally inoculated with JEV genotype Ib. These pigs were derived from crossing miniature domestic pig with four strains of feral pigs and were used since obtaining feral swine was not possible. Results: The Sinclair miniature pigs became viremic and displayed pathological outcomes similar to those observed in domestic swine. Conclusion: Based on these findings, we conclude that in the event of JEV being introduced into the United States, feral pig populations could contribute to establishment and maintenance of a transmission cycle of JEV and could lead to the virus becoming endemic in the United States.

The intentions of information sources can affect what information people think qualifies as true.

The concept of truth is at the core of science, journalism, law, and many other pillars of modern society. Yet, given the imprecision of natural language, deciding what information should count as true is no easy task, even with access to the ground truth. How do people decide whether a given claim of fact qualifies as true or false? Across two studies (N = 1181; 16,248 observations), participants saw claims of fact alongside the ground truth about those claims. Participants classified each claim as true or false. Although participants knew precisely how accurate the claims were, participants classified claims as false more often when they judged the information source to be intending to deceive (versus inform) their audience, and classified claims as true more often when they judged the information source to be intending to provide an approximate (versus precise) account. These results suggest that, even if people have access to the same set of facts, they might disagree about the truth of claims if they attribute discrepant intentions to information sources. Such findings may shed light on the robust and persistent disagreements over claims of fact that have arisen in the "post-truth era".

Association between obsessive-compulsive disorder and the risk of schizophrenia using the Korean National Health Insurance Service-National Sample Cohort: a retrospective cohort study.

AIMS: Obsessive-compulsive disorder (OCD) and schizophrenia are often reported as co-morbid conditions. However, the evidence of an association between OCD and the risk of schizophrenia is limited. This study investigated the risk of schizophrenia in patients newly diagnosed with OCD using a nationally representative sample cohort in South Korea. METHODS: Data were obtained from the 2002-2013 Korean National Health Insurance Service-National Sample Cohort of the National Health Insurance Service. Using propensity score matching, 2509 patients with OCD and a control group of 7527 patients were included in the analysis. Chi-squared tests were used to investigate and compare the general characteristics of the study population. The risk of schizophrenia was analysed using the Cox proportional hazard model. RESULTS: The incidence rate was 45.79/10 000 person-year for patients with OCD and 4.19/10 000 person-year for patients without OCD. Patients with OCD had a higher risk of schizophrenia compared to the control group after adjusting for covariates (hazard ratio = 10.46, 95% confidence interval = 6.07-18.00). CONCLUSIONS: This study identified an association between the diagnosis of OCD and the risk of schizophrenia in a South Korean national representative cohort. Further research using a prospective design to clarify the causality of OCD in schizophrenia in a controlled environment should be conducted to validate these findings.

Comparison of Immunogenicity Between a Candidate Live Attenuated Vaccine and an Inactivated Vaccine for Cache Valley Virus.

Cache Valley virus (CVV) is a mosquito-borne bunyavirus that is enzootic throughout the new world. Although CVV is known as an important agricultural pathogen, primarily associated with embryonic lethality and abortions in ruminants, it has recently been recognized for its expansion as a zoonotic pathogen. With the increased emergence of bunyaviruses with human and veterinary importance, there have been significant efforts dedicated to the development of bunyavirus vaccines. In this study, the immunogenicity of a candidate live-attenuated vaccine (LAV) for CVV, which contains the deletion of the nonstructural small (NSs) and nonstructural medium (NSm) genes (2delCVV), was evaluated and compared with an autogenous candidate vaccine created through the inactivation of CVV using binary ethylenimine (BEI) with an aluminum hydroxide adjuvant (BEI-CVV) in sheep. Both 2delCVV and BEI-CVV produced a neutralizing antibody response that exceeds the correlate of protection, that is, plaque reduction neutralization test titer >10. However, on day 63 postinitial immunization, 2delCVV was more immunogenic than BEI-CVV. These results warrant further development of 2delCVV as a candidate LAV and demonstrate that the double deletion of the NSs and NSm genes can be applied to the development of vaccines and as a common attenuation strategy for orthobunyaviruses.

Indicative factors for surgical or angiographic intervention in hemodynamically stable patients with blunt abdominal trauma: A retrospective cohort study.

INTRODUCTION: The standard of care for intraperitoneal injury in hemodynamically stable patients after blunt abdominal trauma has been replaced by non-operative management (NOM). However, selective NOM, depending on the situation, seems necessary in determining the treatment plan. In this study, we attempted to identify risk factors for surgical or angiographic intervention (SAI) in hemodynamically stable blunt abdominal trauma patients. METHODS: This retrospective study which included adult patients who were brought to a regional trauma center was conducted from March 2015 to October 2019. We evaluated the characteristics of blunt abdominal trauma patients and analyzed factors that were related to the requirement of SAI in these patients. Patients were divided into SAI and conservative management (CM) groups. RESULTS: We reviewed 1,176 patients, and after exclusions, of whom 248 blunt abdominal trauma and free fluid observed on CT were identified. The mean pulse rate was higher in the SAI than in the CM (P=0.025). Laboratory findings showed that lactate and delta neutrophil index (DNI) levels were higher in the SAI than in the CM (P=0.002 and 0.026 respectively). Additionally, the mean free fluid size in the SAI (85.69mm) was significantly larger than that in the CM (68.12mm; P=0.001), and blush was more frequently observed in the SAI (P<0.001). In multivariate analysis, only blush was an independent prognostic factor for SAI (OR 11.7, 95% CI, 5.1-30.8, P<0.001). CONCLUSION: In hemodynamically stable patients with blunt abdominal trauma, blush but also high lactate and DNI are associated with the requirement of interventional radiology and/or surgery.

Immunogenicity of a Candidate Live Attenuated Vaccine for Rift Valley Fever Virus with a Two-Segmented Genome.

Rift Valley fever virus (RVFV) is an emerging arbovirus that affects both ruminants and humans. RVFV causes severe and recurrent outbreaks in Africa and the Arabian Peninsula with a significant risk for emergence into new locations. Although there are a variety of RVFV veterinary vaccines for use in endemic areas, there is currently no licensed vaccine for human use; therefore, there is a need to develop and assess new vaccines. Herein, we report a live-attenuated recombinant vaccine candidate for RVFV, based on the previously described genomic reconfiguration of the conditionally licensed MP12 vaccine. There are two general strategies used to develop live-attenuated RVFV vaccines, one being serial passage of wild-type RVFV strains to select attenuated mutants such as Smithburn, Clone 13, and MP12 vaccine strains. The second strategy has utilized reverse genetics to attenuate RVFV strains by introducing deletions or insertions within the viral genome. The novel candidate vaccine characterized in this report contains a two-segmented genome that lacks the medium viral segment (M) and two virulence genes (nonstructural small and nonstructural medium). The vaccine candidate, named r2segMP12, was evaluated for the production of neutralizing antibodies to RVFV in outbred CD-1 mice. The immune response induced by the r2segMP12 vaccine candidate was directly compared to the immune response induced by the rMP12 parental strain vaccine. Our study demonstrated that a single immunization with the r2segMP12 vaccine candidate at 105 plaque-forming units elicited a higher neutralizing antibody response than the rMP12 vaccine at the same vaccination titer without the need for a booster.

Replication Kinetics of a Candidate Live-Attenuated Vaccine for Cache Valley Virus in Aedes albopictus.

Background: The emergence or re-emergence of several orthobunyaviruses (order: Bunyavirales; family: Peribunyaviridae), including Cache Valley virus (CVV) and Oropouche virus, warrants the development and evaluation of candidate live-attenuated vaccines (LAVs). Ideally, these vaccines would elicit long-lasting immunity with one single immunization. Materials and Methods: Since the deletion of two virulence factors, NSs and NSm, has been shown to attenuate the virulence phenotype of orthobunyaviruses, phleboviruses, and nairoviruses, genetic manipulation of the viral genome is considered an effective strategy for the rational design of candidate LAVs for bunyaviruses across multiple families. In addition, the deletion of Rift Valley fever virus NSs and NSm genes has been shown to reduce transmission by mosquitoes. Results: In this study, the ability of a CVV mutant lacking the NSs and NSm genes (2delCVV) to replicate in intrathoracically injected Aedes albopictus was compared with the parental wild-type CVV (wtCVV) 6V633 strain. In contrast to the robust replication of wtCVV in injected mosquitoes, the multiplication kinetics of the 2delCVV mutant was reduced by more than a 100-fold. Conclusion: These results suggest that the deletion of NSm and NSs genes is a feasible approach to rationally design candidate orthobunyavirus LAVs that are highly attenuated in mosquitoes and, therefore, pose little risk of reversion to virulence and transmission.

Ion beam figuring with focused anode layer thruster.

This work presents the peculiarities of cone ion beam formation with a focused thruster with anode layer (TAL) and its application to silicon carbide (SiC) ion beam figuring. Modeling results of Lorentz E × B force distribution in the discharge gap are presented. 3D particle tracing for keV Ar ions is carried out for the first time in the beam drift region of TAL with magnetic lens. Extracted ion beam full width at half maxima is about 2 mm in the focal plane, where the SiC etching rate reaches 0.5 µm/min. The SiC sputter yields are measured as a function of the Ar ion impact energy and beam incidence angle. The maximum sputter yield of 2.8 atom/ion is observed at 45° of the beam-sample angle for the Si targets. Furthermore, the maximum sputter yield value of 1.7 atom/ion is measured at 30° of the beam-sample angle for the SiC targets. The novelty of present research is in the application of focused TAL keV Ar ion beam to the SiC ion beam figuring.

Inactivation of SARS-CoV-2 in All Blood Components Using Amotosalen/Ultraviolet A Light and Amustaline/Glutathione Pathogen Reduction Technologies.

No cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transfusion-transmitted infections (TTI) have been reported. The detection of viral RNA in peripheral blood from infected patients and blood components from infected asymptomatic blood donors is, however, concerning. This study investigated the efficacy of the amotosalen/UVA light (A/UVA) and amustaline (S-303)/glutathione (GSH) pathogen reduction technologies (PRT) to inactivate SARS-CoV-2 in plasma and platelet concentrates (PC), or red blood cells (RBC), respectively. Plasma, PC prepared in platelet additive solution (PC-PAS) or 100% plasma (PC-100), and RBC prepared in AS-1 additive solution were spiked with SARS-CoV-2 and PR treated. Infectious viral titers were determined by plaque assay and log reduction factors (LRF) were determined by comparing titers before and after treatment. PR treatment of SARS-CoV-2-contaminated blood components resulted in inactivation of the infectious virus to the limit of detection with A/UVA LRF of >3.3 for plasma, >3.2 for PC-PAS-plasma, and >3.5 for PC-plasma and S-303/GSH LRF > 4.2 for RBC. These data confirm the susceptibility of coronaviruses, including SARS-CoV-2 to A/UVA treatment. This study demonstrates the effectiveness of the S-303/GSH treatment to inactivate SARS-CoV-2, and that PRT can reduce the risk of SARS-CoV-2 TTI in all blood components.

Re-Examining the Importance of Pigs in the Transmission of Japanese Encephalitis Virus.

Japanese encephalitis virus (JEV), a mosquito-borne flavivirus, is the leading cause of pediatric encephalitis in Southeast Asia. The enzootic transmission of JEV involves two types of amplifying hosts, swine and avian species. The involvement of pigs in the transmission cycle makes JEV a unique pathogen because human Japanese encephalitis cases are frequently linked to the epizootic spillover from pigs, which can not only develop viremia to sustain transmission but also signs of neurotropic and reproductive disease. The existing knowledge of the epidemiology of JEV largely suggests that viremic pigs are a source of infectious viruses for competent mosquito species, especially Culex tritaeniorhynchus in the endemic regions. However, several recently published studies that applied molecular detection techniques to the characterization of JEV pathogenesis in pigs described the shedding of JEV through multiple routes and persistent infection, both of which have not been reported in the past. These findings warrant a re-examination of the role that pigs are playing in the transmission and maintenance of JEV. In this review, we summarize discoveries on the shedding of JEV during the course of infection and analyze the available published evidence to discuss the possible role of the vector-free JEV transmission route among pigs in viral maintenance.

SARS-CoV-2 and Arthropods: A Review.

The emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that led to the unprecedented COVID-19 pandemic exemplifies how a lack of understanding and preparedness for emerging viruses can result in consequences on a global scale. Statements that SARS-CoV-2 could not be transmitted by arthropod vectors were made without experimental support. Here we review laboratory-based research, field studies, and environmental studies to evaluate the potential for the virus to be transmitted either biologically or mechanically by arthropods. Based on these data, we conclude that transmission by arthropods is highly unlikely to play a significant epidemiological role in the transmission of SARS-CoV-2.

Interventions to mitigate COVID-19 misinformation: protocol for a scoping review.

BACKGROUND: The duration and impact of the COVID-19 pandemic depends in a large part on individual and societal actions which is influenced by the quality and salience of the information to which they are exposed. Unfortunately, COVID-19 misinformation has proliferated. To date, no systematic efforts have been made to evaluate interventions that mitigate COVID-19-related misinformation. We plan to conduct a scoping review that seeks to fill several of the gaps in the current knowledge of interventions that mitigate COVID-19-related misinformation. METHODS: A scoping review focusing on interventions that mitigate COVID-19 misinformation will be conducted. We will search (from January 2020 onwards) MEDLINE, EMBASE, CINAHL, PsycINFO, Web of Science Core Collection, Africa-Wide Information, Global Health, WHO Global Literature on Coronavirus Disease Database, WHO Global Index Medicus, and Sociological Abstracts. Gray literature will be identified using Disaster Lit, Google Scholar, Open Science Framework, governmental websites, and preprint servers (e.g., EuropePMC, PsyArXiv, MedRxiv, JMIR Preprints). Study selection will conform to Joanna Briggs Institute Reviewers' Manual 2020 Methodology for JBI Scoping Reviews. Only English language, original studies will be considered for inclusion. Two reviewers will independently screen all citations, full-text articles, and abstract data. A narrative summary of findings will be conducted. Data analysis will involve quantitative (e.g., frequencies) and qualitative (e.g., content and thematic analysis) methods. DISCUSSION: Original research is urgently needed to design interventions to mitigate COVID-19 misinformation. The planned scoping review will help to address this gap. SYSTEMATIC REVIEW REGISTRATIONS: Systematic Review Registration: Open Science Framework (osf/io/etw9d).

Impact of COVID-19 on CT-diagnosed acute appendicitis and diverticulitis: was there collateral damage?

AIM: To evaluate the change in diagnosis rates, disease severity at presentation, and treatment of acute appendicitis and diverticulitis during the COVID-19 shutdown. MATERIALS AND METHODS: Following institutional review board approval, 6,002 CT examinations performed at five hospitals for suspected acute appendicitis and/or diverticulitis over the 12 weeks preceding and following the shutdown were reviewed retrospectively. Semi-automated language analysis (SALA) of the report classified 3,676 CT examinations as negative. Images of the remaining 2,326 CT examinations were reviewed manually and classified as positive or negative. Positive cases were graded as non-perforated; perforated, contained; and perforated, free. RESULTS: CT examinations performed for suspected appendicitis and/or diverticulitis decreased from 3,558 to 2,200 following the shutdown. The rates of positive diagnoses before and after shutdown were 4% (144) and 4% (100) for appendicitis and 8% (284) and 7% (159) for diverticulitis (p>0.2 for both). For positive CT examinations, the rates of perforation, hospitalisation, surgery, and catheter drainage changed by -2%, -3%, -2%, and -3% for appendicitis (n=244, p>0.3 for all) and +6% (p=0.2) +9% (p=0.06), +4% (p=0.01) and +1% (p=0.6) for diverticulitis (n=443). CONCLUSION: CT examinations performed for suspected appendicitis or diverticulitis declined after the shutdown, likely reflecting patients leaving urban centres and altered triage of non-COVID-19 patients. The diagnosis rates, disease severity at presentation, and treatment approach otherwise remained mostly unchanged.

COVID-19 vaccine perceptions in the initial phases of US vaccine roll-out: an observational study on reddit.

BACKGROUND: Open online forums like Reddit provide an opportunity to quantitatively examine COVID-19 vaccine perceptions early in the vaccine timeline. We examine COVID-19 misinformation on Reddit following vaccine scientific announcements, in the initial phases of the vaccine timeline. METHODS: We collected all posts on Reddit (reddit.com) from January 1 2020 - December 14 2020 (n=266,840) that contained both COVID-19 and vaccine-related keywords. We used topic modeling to understand changes in word prevalence within topics after the release of vaccine trial data. Social network analysis was also conducted to determine the relationship between Reddit communities (subreddits) that shared COVID-19 vaccine posts, and the movement of posts between subreddits. RESULTS: There was an association between a Pfizer press release reporting 90% efficacy and increased discussion on vaccine misinformation. We observed an association between Johnson and Johnson temporarily halting its vaccine trials and reduced misinformation. We found that information skeptical of vaccination was first posted in a subreddit (r/Coronavirus) which favored accurate information and then reposted in subreddits associated with antivaccine beliefs and conspiracy theories (e.g. conspiracy, NoNewNormal). CONCLUSIONS: Our findings can inform the development of interventions where individuals determine the accuracy of vaccine information, and communications campaigns to improve COVID-19 vaccine perceptions, early in the vaccine timeline. Such efforts can increase individual- and population-level awareness of accurate and scientifically sound information regarding vaccines and thereby improve attitudes about vaccines, especially in the early phases of vaccine roll-out. Further research is needed to understand how social media can contribute to COVID-19 vaccination services.

Impact of yellow fever virus envelope protein on wild-type and vaccine epitopes and tissue tropism.

The envelope (E) protein of flaviviruses is functionally associated with viral tissue tropism and pathogenicity. For yellow fever virus (YFV), viscerotropic disease primarily involving the liver is pathognomonic for wild-type (WT) infection. In contrast, the live-attenuated vaccine (LAV) strain 17D does not cause viscerotropic disease and reversion to virulence is associated with neurotropic disease. The relationship between structure-function of the E protein for WT strain Asibi and its LAV derivative 17D strain is poorly understood; however, changes to WT and vaccine epitopes have been associated with changes in virulence. Here, a panel of Asibi and 17D infectious clone mutants were generated with single-site mutations at the one membrane residue and each of the eight E protein amino acid substitutions that distinguish the two strains. The mutants were characterized with respect to WT-specific and vaccine-specific monoclonal antibodies (mAbs) binding to virus plus binding of virus to brain, liver, and lung membrane receptor preparations (MRPs) generated from AG129 mice. This approach shows that amino acids in the YFV E protein domains (ED) I and II contain the WT E protein epitope, which overlap with those that mediate YFV binding to mouse liver. Furthermore, amino acids in EDIII associated with the vaccine epitope overlap with those that facilitate YFV binding mouse brain MRPs. Taken together, these data suggest that the YFV E protein is a key determinant in the phenotype of WT and 17D vaccine strains of YFV.

The Politicization of Health and Science: Role of Political Cues in Shaping the Beliefs of the Vaccine-Autism Link.

One critical lesson learned from public opinion research about climate change is that the cost of politicization is disastrous. Although the literature has shown the dire consequences of politicized science issues, few have examined how such politicization is possibly triggered by political leaders in a seemingly nonpartisan science topic. Using two experiments (total n = 1,249), this article demonstrates how political cues over scientific expertise shape individuals' beliefs in the vaccine and autism debate. The results indicate that Republicans tend to follow President Trump compared to scientists in the subject matter. On the other hand, Democrats follow scientists but are not influenced by Trump. The implications of political encroachment into health and science are discussed.