HIV-1 competition experiments in humanized mice show that APOBEC3H imposes selective pressure and promotes virus adaptation

APOBEC3 (A3) family proteins are DNA cytosine deaminases recognized for contributing to HIV-1 restriction and mutation. Prior studies have demonstrated that A3D, A3F, and A3G enzymes elicit a robust anti-HIV-1 effect in cell cultures and in humanized mouse models. Human A3H is polymorphic and can be categorized into three phenotypes: stable, intermediate, and unstable. However, the anti-viral effect of endogenous A3H in vivo has yet to be examined. Here we utilize a hematopoietic stem cell-transplanted humanized mouse model and demonstrate that stable A3H robustly affects HIV-1 fitness in vivo. In contrast, the selection pressure mediated by intermediate A3H is relaxed. Intriguingly, viral genomic RNA sequencing reveled that HIV-1 frequently adapts to better counteract stable A3H during replication in humanized mice. Molecular phylogenetic analyses and mathematical modeling suggest that stable A3H may be a critical factor in human-to-human viral transmission. Taken together, this study provides evidence that stable variants of A3H impose selective pressure on HIV-1

The conservation impacts of ecological disturbance:Time-bound estimates of population loss and recovery for fauna affected by the 2019–2020 Australian megafires

Aim: After environmental disasters, species with large population losses may need urgent protection to prevent extinction and support recovery. Following the 2019-2020 Australian megafires, we estimated population losses and recovery in fire-affected fauna, to inform conservation status assessments and management. Location: Temperate and subtropical Australia. Time period 2019-2030 and beyond. Major taxa: Australian terrestrial and freshwater vertebrates; one invertebrate group. Methods: From > 1,050 fire-affected taxa, we selected 173 whose distributions substantially overlapped the fire extent. We estimated the proportion of each taxon's distribution affected by fires, using fire severity and aquatic impact mapping, and new distribution mapping. Using expert elicitation informed by evidence of responses to previous wildfires, we estimated local population responses to fires of varying severity. We combined the spatial and elicitation data to estimate overall population loss and recovery trajectories, and thus indicate potential eligibility for listing as threatened, or uplisting, under Australian legislation. Results: We estimate that the 2019-2020 Australian megafires caused, or contributed to, population declines that make 70-82 taxa eligible for listing as threatened; and another 21-27 taxa eligible for uplisting. If so-listed, this represents a 22-26% increase in Australian statutory lists of threatened terrestrial and freshwater vertebrates and spiny crayfish, and uplisting for 8-10% of threatened taxa. Such changes would cause an abrupt worsening of underlying trajectories in vertebrates, as measured by Red List Indices. We predict that 54-88% of 173 assessed taxa will not recover to pre-fire population size within 10 years/three generations. Main conclusions We suggest the 2019-2020 Australian megafires have worsened the conservation prospects for many species. Of the 91 taxa recommended for listing/uplisting consideration, 84 are now under formal review through national processes. Improving predictions about taxon vulnerability with empirical data on population responses, reducing the likelihood of future catastrophic events and mitigating their impacts on biodiversity, are critical