The E2 glycoprotein holds key residues for Mayaro virus adaptation to the urban Aedes aegypti mosquito.

Adaptation to mosquito vectors suited for transmission in urban settings is a major driver in the emergence of arboviruses. To better anticipate future emergence events, it is crucial to assess their potential to adapt to new vector hosts. In this work, we used two different experimental evolution approaches to study the adaptation process of an emerging alphavirus, Mayaro virus (MAYV), to Ae. aegypti, an urban mosquito vector of many other arboviruses. We identified E2-T179N as a key mutation increasing MAYV replication in insect cells and enhancing transmission after escaping the midgut of live Ae. aegypti. In contrast, this mutation decreased viral replication and binding in human fibroblasts, a primary cellular target of MAYV in humans. We also showed that MAYV E2-T179N generates reduced viremia and displays less severe tissue pathology in vivo in a mouse model. We found evidence in mouse fibroblasts that MAYV E2-T179N is less dependent on the Mxra8 receptor for replication than WT MAYV. Similarly, exogenous expression of human apolipoprotein receptor 2 and Mxra8 enhanced WT MAYV replication compared to MAYV E2-T179N. When this mutation was introduced in the closely related chikungunya virus, which has caused major outbreaks globally in the past two decades, we observed increased replication in both human and insect cells, suggesting E2 position 179 is an important determinant of alphavirus host-adaptation, although in a virus-specific manner. Collectively, these results indicate that adaptation at the T179 residue in MAYV E2 may result in increased vector competence-but coming at the cost of optimal replication in humans-and may represent a first step towards a future emergence event.

Development and Feasibility of an Online Brief Emotion Regulation Training (BERT) Program for Emerging Adults.

Mental wellness is a critical component of healthy development in emerging adulthood and serves to protect against stress and promote resilience against psychopathology. Emotion regulation is a key mechanism for effective prevention because of its role in socio-emotional competence and its transdiagnostic significance for psychopathology. In this feasibility study, a brief, time and cost-effective emotion regulation training program for emerging adults (BERT) was developed and tested using the RE-AIM framework. Importantly, building interventions within the context of an implementation framework, such as the RE-AIM framework, enhances the chances that an intervention will be able to scale out and scale up. First, the brainwriting premortem method was utilized to refine program content, conducting focus groups a priori to identify potential program failures prior to program implementation. Undergraduate students (n = 12) attended four focus groups presenting initial program content. Four clinicians were also interviewed to determine program barriers. Qualitative analyses aggregated participant feedback to identify compliments, changes, and concerns about BERT and critical feedback was immediately implemented prior to initial testing. BERT was rooted in cognitive-behavioral practices and informed by the Gross model of emotion regulation. The 5-week program was then examined in a college sample (N = 42) to evaluate implementation (low attrition, high content engagement, favorable attitudes, low incidence of technical errors, costs), reach (enrollment and completion demographics comparable to the population in which recruitment took place), and efficacy (positive change in emotion regulation pre- to post-program). Of the recruited participants, 36 remained in the study where 27 completed at least 80% of program content. Repeated-measures ANOVAs exhibited significant improvements in emotion regulation, psychological distress, and negative affectivity, suggesting promising initial efficacy. Initial data provide support for feasibility and a future randomized control trial. BERT has potential significance for promoting healthy development as its brief electronic format reduced barriers and the program development process incorporated stakeholder feedback at multiple levels to inform better implementation and dissemination.