The HIV-1 Protein Vpr Targets the Endoribonuclease Dicer for Proteasomal Degradation to Boost Macrophage Infection

The HIV-1 protein Vpr enhances macrophage infection, triggers G2 cell cycle arrest, and targets cells for NK-cell killing. Vpr acts through the CRL4DCAF1 ubiquitin ligase complex to cause G2 arrest and trigger expression of NK ligands. Corresponding ubiquitination targets have not been identified. UNG2 and SMUG1 are the only known substrates for Vpr-directed depletion through CRL4DCAF1. Here we identify the endoribonuclease Dicer as a target of HIV-1 Vpr-directed proteasomal degradation through CRL4DCAF1. We show that HIV-1 Vpr inhibits short hairpin RNA function as expected upon reduction of Dicer levels. Dicer inhibits HIV-1 replication in T cells. We demonstrate that Dicer also restricts HIV-1 replication in human monocyte-derived macrophages (MDM) and that reducing Dicer expression in MDMs enhances HIV-1 infection in a Vpr-dependent manner. Our results support a model in which Vpr complexes with human Dicer to boost its interaction with the CRL4DCAF1 ubiquitin ligase complex and its subsequent degradation

HIV-1 Vpr Enhances Viral Burden by Facilitating Infection of Tissue Macrophages but Not Nondividing CD4+ T Cells

Prior experiments in explants of human lymphoid tissue have demonstrated that human immunodeficiency virus type 1 (HIV-1) productively infects diverse cellular targets including T cells and tissue macrophages. We sought to determine the specific contribution of macrophages and T cells to the overall viral burden within lymphoid tissue. To block infection of macrophages selectively while preserving infection of T cells, we used viruses deficient for viral protein R (Vpr) that exhibit profound replication defects in nondividing cells in vitro. We inoculated tonsil histocultures with matched pairs of congenic viruses that differed only by the presence of a wild-type or truncated vpr gene. Although these viruses exhibited no reduction in the infection or depletion of T cells, the ability of the Vpr-deficient R5 virus to infect tissue macrophages was severely impaired compared with matched wild-type R5 virus. Interestingly, the Vpr-deficient R5 virus also exhibited a 50% reduction in overall virus replication compared with its wild-type counterpart despite the fact that macrophages represent a small fraction of the potential targets of HIV-1 infection in these tissues. Collectively, these data highlight the importance of tissue macrophages in local viral burden and further implicate roles for CC chemokine receptor 5, macrophages, and Vpr in the life cycle and pathogenesis of HIV-1

Estruturas de governança em arranjos produtivos locais: um estudo comparativo nos arranjos calçadistas e sucroalcooleiro no estado de São Paulo

A governança nos arranjos produtivos refere-se ao modo de coordenação, comando, intervenção e participação dos atores do arranjo. Devido ao significativo aumento do interesse da política pública em arranjos produtivos locais no Brasil, é oportuno compreender essa variação e/ou interdependência de governança de cada arranjo territorial. O presente artigo compara estruturas de governança em três arranjos produtivos locais (APLs): a) Birigui (calçados infantis), b) Jaú (calçados femininos) e c) Piracicaba (APL do álcool). A coleta de dados em organizações de interesses e em 31 empresas dos três arranjos paulistas foi realizada por entrevistas em profundidade in loco nas empresas. No artigo são identificadas as influências distintas nas governanças dos arranjos produtivos. Os resultados da pesquisa revelam: 1) a governança teve interferência positiva na cooperação e no desenvolvimento de empresas; 2) as possibilidades de desenvolvimento dos APLs dependem em grande parte das formas de governança pública ou privada; 3) as governanças desses arranjos produtivos locais são heterogêneas, complexas e, em alguns casos, interdependentes com outras distintas; e 4) os atores coordenadores dos arranjos determinam as relações, recursos e regras, propondo novas ordens institucionais e organizacionais

Local hydrological conditions influence tree diversity and composition across the Amazon basin

Tree diversity and composition in Amazonia are known to be strongly determined by the water supplied by precipitation. Nevertheless, within the same climatic regime, water availability is modulated by local topography and soil characteristics (hereafter referred to as local hydrological conditions), varying from saturated and poorly drained to well-drained and potentially dry areas. While these conditions may be expected to influence species distribution, the impacts of local hydrological conditions on tree diversity and composition remain poorly understood at the whole Amazon basin scale. Using a dataset of 443 1-ha non-flooded forest plots distributed across the basin, we investigate how local hydrological conditions influence 1) tree alpha diversity, 2) the community-weighted wood density mean (CWM-wd) – a proxy for hydraulic resistance and 3) tree species composition. We find that the effect of local hydrological conditions on tree diversity depends on climate, being more evident in wetter forests, where diversity increases towards locations with well-drained soils. CWM-wd increased towards better drained soils in Southern and Western Amazonia. Tree species composition changed along local soil hydrological gradients in Central-Eastern, Western and Southern Amazonia, and those changes were correlated with changes in the mean wood density of plots. Our results suggest that local hydrological gradients filter species, influencing the diversity and composition of Amazonian forests. Overall, this study shows that the effect of local hydrological conditions is pervasive, extending over wide Amazonian regions, and reinforces the importance of accounting for local topography and hydrology to better understand the likely response and resilience of forests to increased frequency of extreme climate events and rising temperatures