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1.
PLoS Pathog ; 19(1): e1011080, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36634147

RESUMO

Kaposi's sarcoma-associated herpesvirus (KSHV) causes the inflammatory and angiogenic endothelial cell neoplasm, Kaposi's sarcoma (KS). We previously demonstrated that the KSHV Kaposin B (KapB) protein promotes inflammation via the disassembly of cytoplasmic ribonucleoprotein granules called processing bodies (PBs). PBs modify gene expression by silencing or degrading labile messenger RNAs (mRNAs), including many transcripts that encode inflammatory or angiogenic proteins associated with KS disease. Although our work implicated PB disassembly as one of the causes of inflammation during KSHV infection, the precise mechanism used by KapB to elicit PB disassembly was unclear. Here we reveal a new connection between the degradative process of autophagy and PB disassembly. We show that both latent KSHV infection and KapB expression enhanced autophagic flux via phosphorylation of the autophagy regulatory protein, Beclin. KapB was necessary for this effect, as infection with a recombinant virus that does not express the KapB protein did not induce Beclin phosphorylation or autophagic flux. Moreover, we showed that PB disassembly mediated by KSHV or KapB, depended on autophagy genes and the selective autophagy receptor NDP52/CALCOCO2 and that the PB scaffolding protein, Pat1b, co-immunoprecipitated with NDP52. These studies reveal a new role for autophagy and the selective autophagy receptor NDP52 in promoting PB turnover and the concomitant synthesis of inflammatory molecules during KSHV infection.


Assuntos
Infecções por Herpesviridae , Herpesvirus Humano 8 , Sarcoma de Kaposi , Humanos , Autofagia , Células Endoteliais/metabolismo , Infecções por Herpesviridae/metabolismo , Herpesvirus Humano 8/genética , Corpos de Processamento , Proteínas Nucleares/metabolismo
2.
Semin Nephrol ; 37(3): 211-223, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28532551

RESUMO

In Africa, the combination of noncommunicable diseases, infectious diseases, exposure to environmental toxins, and acute kidney injury related to trauma and childbirth are driving an epidemic of chronic kidney disease and end-stage renal disease (ESRD). Good registry data can inform the planning of renal services and can be used to argue for better resource allocation, audit the delivery and quality of care, and monitor the impact of interventions. Few African countries have established renal registries and most have failed owing to resource constraints. In this article we briefly review the burden of chronic kidney disease and ESRD in Africa, and then consider the research questions that could be addressed by renal registries. We describe examples of the impact of registry data and summarize the sparse primary literature on country-wide renal replacement therapy in African countries over the past 20 years. Finally, we highlight some initiatives and opportunities for strengthening research on ESRD and renal replacement therapy in Africa. These include the establishment of the African Renal Registry and the availability of new areas for research. We also discuss capacity building, collaboration, open-access publication, and the strengthening of local journals, all measures that may improve the quantity, visibility, and impact of African research outputs.


Assuntos
Pesquisa Biomédica/normas , Falência Renal Crônica , Indicadores de Qualidade em Assistência à Saúde/organização & administração , Sistema de Registros/normas , África/epidemiologia , Pesquisa Biomédica/tendências , Humanos , Falência Renal Crônica/classificação , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/terapia , Morbidade/tendências
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