HIV-1 capsid stability enables inositol phosphate-independent infection of target cells and promotes integration into genes.

The mature HIV-1 capsid is stabilized by host and viral determinants. The capsid protein CA binds to the cellular metabolites inositol hexakisphosphate (IP6) and its precursor inositol (1, 3, 4, 5, 6) pentakisphosphate (IP5) to stabilize the mature capsid. In target cells, capsid destabilization by the antiviral compounds lenacapavir and PF74 reveals a HIV-1 infectivity defect due to IP5/IP6 (IP5/6) depletion. To test whether intrinsic HIV-1 capsid stability and/or host factor binding determines HIV-1 insensitivity to IP5/6 depletion, a panel of CA mutants was assayed for infection of IP5/6-depleted T cells and wildtype cells. Four CA mutants with unstable capsids exhibited dependence on host IP5/6 for infection and reverse transcription (RTN). Adaptation of one such mutant, Q219A, by spread in culture resulted in Vpu truncation and a capsid three-fold interface mutation, T200I. T200I increased intrinsic capsid stability as determined by in vitro uncoating of purified cores and partially reversed the IP5/6-dependence in target cells for each of the four CA mutants. T200I further rescued the changes to lenacapavir sensitivity associated with the parental mutation. The premature dissolution of the capsid caused by the IP5/6-dependent mutations imparted a unique defect in integration targeting that was rescued by T200I. Collectively, these results demonstrate that T200I restored other capsid functions after RTN for the panel of mutants. Thus, the hyperstable T200I mutation stabilized the instability defects imparted by the parental IP5/6-dependent CA mutation. The contribution of Vpu truncation to mutant adaptation was linked to BST-2 antagonization, suggesting that cell-to-cell transfer promoted replication of the mutants. We conclude that interactions at the three-fold interface are adaptable, key mediators of capsid stability in target cells and are able to antagonize even severe capsid instability to promote infection.

Teams in Transition: A Three-Wave Longitudinal Study of Reflection, Implicit and Explicit Coordination and Performance Improvements.

Research has shown that team reflection is a critical transition process for coordination processes and team performance, but our understanding of its dynamics and relationship to action processes and performance is incomplete. The goal of the present study was to examine the long-term change in reflection in teams over time and explore whether these changes are related to implicit and explicit coordination processes and performance improvement. Drawing on the recurring phase model of team processes and team reflexivity theory, we hypothesized that team reflection is at least stable or increases over time for dissimilar tasks, that reflection trajectories are positively associated with implicit and negatively associated with explicit coordination in the later phases, and that implicit coordination mediates the relationship between team reflection and performance improvement. This model was tested in a three-wave longitudinal study (N = 175 teams) over a 2-months period. Results from growth curve modeling and structural equation modeling provided support for our hypotheses.

Ecological and cultural factors underlying the global distribution of prejudice.

Prejudiced attitudes and political nationalism vary widely around the world, but there has been little research on what predicts this variation. Here we examine the ecological and cultural factors underlying the worldwide distribution of prejudice. We suggest that cultures grow more prejudiced when they tighten cultural norms in response to destabilizing ecological threats. A set of seven archival analyses, surveys, and experiments (∑N = 3,986,402) find that nations, American states, and pre-industrial societies with tighter cultural norms show the most prejudice based on skin color, religion, nationality, and sexuality, and that tightness predicts why prejudice is often highest in areas of the world with histories of ecological threat. People's support for cultural tightness also mediates the link between perceived ecological threat and intentions to vote for nationalist politicians. Results replicate when controlling for economic development, inequality, conservatism, residential mobility, and shared cultural heritage. These findings offer a cultural evolutionary perspective on prejudice, with implications for immigration, intercultural conflict, and radicalization.

Development of a bead-based immunoassay using virus-like particles for detection of alphaviral humoral response.

There is a pressing need for sustainable and sensitive immunodiagnostics for use in public health efforts to understand and combat the threat of endemic and emerging infectious diseases. In this proof-of-concept work, we describe an immunodiagnostic approach based on the utilization of virus-like particles (VLPs) in a magnetic bead-based platform for multiplexed detection of antiviral humoral response. A retroviral-based VLP, that presents Venezuelan equine encephalitis virus E1/E2 glycoprotein antigen on its surface, was synthesized and coupled to magnetic beads to create VLP-conjugated microspheres (VCMs). Using these VCMs, IgM and IgG antibodies were detectable in nonhuman primate (NHP) and human clinical serum samples at dilutions of 1 × 10 Basile et al. [4] and greater. We also extended the VCM methodology to an Old World alphavirus, chikungunya virus, demonstrating the flexibility of this approach toward different VLP architectures. When multiplexed on the MAGPIX® platform, this method provided differential detection between Old World and New World alphaviral IgM. This flexible, immunodiagnostic method, based on the MAGPIX® platform, demonstrates compatibility of particulate antigens with bead-based assays, improves sensitivity by up to 2-logs, and has faster sample-to-answer time over traditional methods.