Viral capsids: Mechanical characteristics, genome packaging and delivery mechanisms

The main functions of viral capsids are to protect, transport and deliver their genome. The mechanical properties of capsids are supposed to be adapted to these tasks. Bacteriophage capsids also need to withstand the high pressures the DNA is exerting onto it as a result of the DNA packaging and its consequent confinement within the capsid. It is proposed that this pressure helps driving the genome into the host, but other mechanisms also seem to play an important role in ejection. DNA packaging and ejection strategies are obviously dependent on the mechanical properties of the capsid. This review focuses on the mechanical properties of viral capsids in general and the elucidation of the biophysical aspects of genome packaging mechanisms and genome delivery processes of double-stranded DNA bacteriophages in particular

Cabotegravir for HIV Prevention in Cisgender Men and Transgender Women

Background: Safe and effective long-acting injectable agents for preexposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) infection are needed to increase the options for preventing HIV infection. Methods: We conducted a randomized, double-blind, double-dummy, noninferiority trial to compare long-acting injectable cabotegravir (CAB-LA, an integrase strand-transfer inhibitor [INSTI]) at a dose of 600 mg, given intramuscularly every 8 weeks, with daily oral tenofovir disoproxil fumarate-emtricitabine (TDF-FTC) for the prevention of HIV infection in at-risk cisgender men who have sex with men (MSM) and in at-risk transgender women who have sex with men. Participants were randomly assigned (1:1) to receive one of the two regimens and were followed for 153 weeks. HIV testing and safety evaluations were performed. The primary end point was incident HIV infection. Results: The intention-to-treat population included 4566 participants who underwent randomization; 570 (12.5%) identified as transgender women, and the median age was 26 years (interquartile range, 22 to 32). The trial was stopped early for efficacy on review of the results of the first preplanned interim end-point analysis. Among 1698 participants from the United States, 845 (49.8%) identified as Black. Incident HIV infection occurred in 52 participants: 13 in the cabotegravir group (incidence, 0.41 per 100 person-years) and 39 in the TDF-FTC group (incidence, 1.22 per 100 person-years) (hazard ratio, 0.34; 95% confidence interval, 0.18 to 0.62). The effect was consistent across prespecified subgroups. Injection-site reactions were reported in 81.4% of the participants in the cabotegravir group and in 31.3% of those in the TDF-FTC group. In the participants in whom HIV infection was diagnosed after exposure to CAB-LA, INSTI resistance and delays in the detection of HIV infection were noted. No safety concerns were identified. Conclusions: CAB-LA was superior to daily oral TDF-FTC in preventing HIV infection among MSM and transgender women. Strategies are needed to prevent INSTI resistance in cases of CAB-LA PrEP failure

Herbivory: effects on plant abundance, distribution and population growth

Plants are attacked by many different consumers. A critical question is how often, and under what conditions, common reductions in growth, fecundity or even survival that occur due to herbivory translate to meaningful impacts on abundance, distribution or dynamics of plant populations. Here, we review population-level studies of the effects of consumers on plant dynamics and evaluate: (i) whether particular consumers have predictably more or less influence on plant abundance, (ii) whether particular plant life-history types are predictably more vulnerable to herbivory at the population level, (iii) whether the strength of plant–consumer interactions shifts predictably across environmental gradients and (iv) the role of consumers in influencing plant distributional limits. Existing studies demonstrate numerous examples of consumers limiting local plant abundance and distribution. We found larger effects of consumers on grassland than woodland forbs, stronger effects of herbivory in areas with high versus low disturbance, but no systematic or unambiguous differences in the impact of consumers based on plant life-history or herbivore feeding mode. However, our ability to evaluate these and other patterns is limited by the small (but growing) number of studies in this area. As an impetus for further study, we review strengths and challenges of population-level studies, such as interpreting net impacts of consumers in the presence of density dependence and seed bank dynamics