Genetic Adaptation by Dengue Virus Serotype 2 to Enhance Infection of Mosquito Midguts.

Dengue viruses (DENVs), serotypes 1-4, are arthropod-borne viruses transmitted to humans by mosquitoes, primarily Aedes aegypti. The transmission cycle begins when ingest blood from a viremic human and the virus infects midgut epithelial cells. In studying viruses derived from the DENV2 infectious clone 30P-NBX, we found that when the virus was delivered to female in an infectious blood meal, the midgut infection rate (MIR) was very low.

Exposing cryptic epitopes on the Venezuelan equine encephalitis virus E1 glycoprotein prior to treatment with alphavirus cross-reactive monoclonal antibody allows blockage of replication early in infection.

Eastern equine encephalitis virus (EEEV), western equine encephalitis virus (WEEV) and Venezuelan equine encephalitis virus (VEEV) can cause fatal encephalitis in humans and equids. Some MAbs to the E1 glycoprotein are known to be cross-reactive, weakly neutralizing in vitro but can protect from disease in animal models. We investigated the mechanism of neutralization of VEEV infection by the broadly cross-reactive E1-specific MAb 1A4B-6.

A Monoclonal Antibody Specific for Japanese Encephalitis Virus with High Neutralizing Capability for Inclusion as a Positive Control in Diagnostic Neutralization Tests.

Japanese encephalitis virus (JEV) is the most common cause of viral encephalitis in Asia, and it is increasingly a global public health concern because of its recent geographic expansion. Although commercial vaccines are available and used in some endemic countries, JEV continues to cause illness, with more than 60,000 cases reported annually. To develop a reproducible positive control antibody useable in diagnosis of JEV infections, murine hybridomas were developed from mice inoculated with a combination of IXIARO JEV vaccine and JEV domain III of the envelope protein (E-DIII).

A DENV-2-type-specific monoclonal antibody binds to the DENV-complex-reactive antigenic site on envelope protein domain 3.

The Dengue virus (DENV) envelope (E) protein is the major component of the viral surface and is structurally subdivided into three domains, ED1, ED2 and ED3. ED3 elicits potent neutralizing antibodies and contains two major antigenic sites: the DENV-type-specific and DENV-complex-reactive antigenic sites. Each site is composed of a limited subset of residues that are required for monoclonal antibody (mAb) binding.

A humanized monoclonal antibody neutralizes yellow fever virus strain 17D-204 in vitro but does not protect a mouse model from disease.

The yellow fever virus (YFV) vaccine 17D-204 is considered safe and effective, yet rare severe adverse events (SAEs), some resulting in death, have been documented following vaccination. Individuals exhibiting post-vaccinal SAEs are ideal candidates for antiviral monoclonal antibody (MAb) therapy; the time until appearance of clinical signs post-exposure is usually short and patients are quickly hospitalized. We previously developed a murine-human chimeric monoclonal antibody (cMAb), 2C9-cIgG, reactive with both virulent YFV and 17D-204, and demonstrated its ability to prevent and treat YF disease in both AG129 mouse and hamster models of infection.

Next generation dengue vaccines: A review of the preclinical development pipeline.

Dengue represents a significant and growing public health problem across the globe, with approximately half of the world's population at risk. The increasing and expanding burden of dengue has highlighted the need for new tools to prevent dengue, including development of dengue vaccines. Recently, the first dengue vaccine candidate was evaluated in Phase 3 clinical trials, and other vaccine candidates are under clinical evaluation.

Locking and blocking the viral landscape of an alphavirus with neutralizing antibodies.

Unlabelled: Alphaviruses are serious, sometimes lethal human pathogens that belong to the family Togaviridae. The structures of human Venezuelan equine encephalitis virus (VEEV), an alphavirus, in complex with two strongly neutralizing antibody Fab fragments (F5 and 3B4C-4) have been determined using a combination of cryo-electron microscopy and homology modeling. We characterize these monoclonal antibody Fab fragments, which are known to abrogate VEEV infectivity by binding to the E2 (envelope) surface glycoprotein.

Molecular determinants of dengue virus 2 envelope protein important for virus entry in FcγRIIA-mediated antibody-dependent enhancement of infection.

Antibody-dependent enhancement (ADE) of infection may cause severe illness in patients suffering a secondary infection by a heterologous dengue virus (DENV) serotype. During ADE of infection, cross-reactive non- or poorly-neutralizing antibodies form infectious virus-Ab complexes with the newly infecting serotype and enhance virus infection by binding to the Fcγ receptors (FcγR) on FcγR-bearing cells. In this study, we determined that molecular determinants of DENV2 envelope protein critical for virus entry during non-ADE infection are also required for ADE infection mediated by FcγRIIA, and binding of virus-Ab complexes with FcγRIIA alone is not sufficient for ADE of infection.

Humanized monoclonal antibody 2C9-cIgG has enhanced efficacy for yellow fever prophylaxis and therapy in an immunocompetent animal model.

Yellow fever virus (YFV) causes significant human disease and mortality in tropical regions of South and Central America and Africa, despite the availability of an effective vaccine. No specific therapy for YF is available. We previously showed that the humanized monoclonal antibody (MAb) 2C9-cIgG provided prophylactic and therapeutic protection from mortality in interferon receptor-deficient strain AG129 mice challenged with YF 17D-204 vaccine.

West nile virus in the United States - a historical perspective.

Prior to 1999, West Nile virus (WNV) was a bit player in the screenplay of global vector-borne viral diseases. First discovered in the West Nile District of Uganda in 1937, this Culex sp.-transmitted virus was known for causing small human febrile outbreaks in Africa and the Middle East.

Development of a small animal peripheral challenge model of Japanese encephalitis virus using interferon deficient AG129 mice and the SA14-14-2 vaccine virus strain.

Japanese encephalitis virus (JEV) is the most common cause of viral encephalitis in Asia, and it is increasingly a global public health concern due to its recent geographic expansion. While commercial vaccines are available and used in some endemic countries, JEV continues to be a public health problem, with 50,000 cases reported annually. Research with virulent JEV in mouse models to develop new methods of prevention and treatment is restricted to BSL-3 containment facilities, confining these studies to investigators with access to these facilities.

BodiMojo: effective Internet-based promotion of positive body image in adolescent girls.

This study tested the efficacy of an Internet-based health promotion program, BodiMojo, designed to promote positive body image in adolescents. Participants were 178 students (mean age 15.2 years, 67.

Race/ethnicity, education, and treatment parameters as moderators and predictors of outcome in binge eating disorder.

Objective: Binge eating disorder (BED) is prevalent among individuals from minority racial/ethnic groups and among individuals with lower levels of education, yet the efficacy of psychosocial treatments for these groups has not been examined in adequately powered analyses. This study investigated the relative variance in treatment retention and posttreatment symptom levels accounted for by demographic, clinical, and treatment variables as moderators and predictors of outcome.

Method: Data were aggregated from 11 randomized, controlled trials of psychosocial treatments for BED conducted at treatment sites across the United States.

Mutation of the dengue virus type 2 envelope protein heparan sulfate binding sites or the domain III lateral ridge blocks replication in Vero cells prior to membrane fusion.

Using an infectious cDNA clone we engineered seven mutations in the putative heparan sulfate- and receptor-binding motifs of the envelope protein of dengue virus serotype 2, strain 16681. Four mutant viruses, KK122/123EE, E202K, G304K, and KKK305/307/310EEE, were recovered following transfection of C6/36 cells. A fifth mutant, KK291/295EE, was recovered from C6/36 cells with a compensatory E295V mutation.

Long-term safety assessment of live attenuated tetravalent dengue vaccines: deliberations from a WHO technical consultation.

Dengue is a rapidly growing public health threat with approximately 2.5 billion people estimated to be at risk. Several vaccine candidates are at various stages of pre-clinical and clinical development.

Application of the radiating effect concept to implement measures stipulated by the European Water Framework Directive.

Hydromorphological deficits of European rivers and creeks are a major reason for the fact that the good ecological status stipulated by the European Water Framework Directive has not been achieved. In order to overcome these deficits, the German state of North Rhine-Westphalia calls for the implementation of a radiating effect concept to facilitate the planning of cost-effective restoration measures. The radiating effect concept states that natural or near-natural sections of water bodies have a positive impact on adjacent hydromorphologically altered sections.

Characteristics of predrinking and associated risks: a survey in a sample of German high school students.

Objectives: Finding predictors for predrinking and placing the new phenomenon of predrinking on a greater database. Predrinking is defined as alcohol consumption, alone or with friends, at home or at public places, before going out in the evening to a party or in bars or discotheques.

Methods: Data were collected from a representative sample of 757 ninth- and tenth-grade students from 31 high schools located in a south German rural region and a city.

Social-cognitive correlates of fruit and vegetable consumption in minority and non-minority youth.

Objective: Inadequate fruit and vegetable (FV) consumption signals a need for identifying predictors and correlates of intake, particularly in diverse adolescents.

Design: Participants completed an on-line assessment in early 2010.

Setting: Computer classrooms in 4 high schools.

Mutations in the West Nile prM protein affect VLP and virion secretion in vitro.

Mutation of the West Nile virus-like particle (WN VLP) prM protein (T20D, K31A, K31V, or K31T) results in undetectable VLP secretion from transformed COS-1 cells. K31 mutants formed intracellular prM-E heterodimers; however these proteins remained in the ER and ER-Golgi intermediary compartments of transfected cells. The T20D mutation affected glycosylation, heterodimer formation, and WN VLP secretion.

Considering J.Lo and Ugly Betty: a qualitative examination of risk factors and prevention targets for body dissatisfaction, eating disorders, and obesity in young Latina women.

Latina women are vulnerable to poor body image, eating disorders, and obesity, particularly during the college years. This study sought to identify common cultural antecedents of these concerns in order to inform the development of prevention programs for this population. Six groups of university students who identified as Latina (N=27) discussed cultural aspects of body image, eating disorders, and obesity.

A small animal peripheral challenge model of yellow fever using interferon-receptor deficient mice and the 17D-204 vaccine strain.

Yellow fever virus (YFV), a member of the genus Flavivirus, is a mosquito-borne pathogen that requires wild-type (wt), virulent strains to be handled at biosafety level (BSL) 3, with HEPA-filtration of room air exhaust (BSL3+). YFV is found in tropical regions of Africa and South America and causes severe hepatic disease and death in humans. Despite the availability of effective vaccines (17D-204 or 17DD), YFV is still responsible for an estimated 200,000 cases of illness and 30,000 deaths annually.

A humanized IgG but not IgM antibody is effective in prophylaxis and therapy of yellow fever infection in an AG129/17D-204 peripheral challenge mouse model.

Yellow fever virus (YFV), a member of the genus Flavivirus, is a mosquito-borne virus found in tropical regions of Africa and South America that causes severe hepatic disease and death in humans. Despite the availability of effective vaccines, YFV is responsible for an estimated 200,000 cases and 30,000 deaths annually. There are currently no prophylactic or therapeutic strategies approved for use in human YFV infections.

Psychometric properties of measures of eating disorder risk in Latina college women.

Objective: Latina college women are at risk for eating disorders (EDs), but assessment is problematic, because the psychometric properties of risk factor measures have not been evaluated with this group.

Method: Reliability and validity estimates of the Eating Disorder Examination Questionnaire, Body Esteem Scale, Sociocultural Attitudes Toward Appearance Questionnaire-3, and Body Shape Questionnaire were examined in a sample of 173 female Latina college students.

Results: Cronbach α coefficients (.

Racial/ethnic differences in adults in randomized clinical trials of binge eating disorder.

Objective: Recent studies suggest that binge eating disorder (BED) is as prevalent among African American and Hispanic Americans as among Caucasian Americans; however, data regarding the characteristics of treatment-seeking individuals from racial and ethnic minority groups are scarce. The purpose of this study was to investigate racial/ethnic differences in demographic characteristics and eating disorder symptoms in participants enrolled in treatment trials for BED.

Method: Data from 11 completed randomized, controlled trials were aggregated in a single database, the Clinical Trials of Binge Eating Disorder (CT-BED) database, which included 1,204 Caucasian, 120 African American, and 64 Hispanic participants assessed at baseline.