RESUMEN
Targeted HIV cure strategies require definition of the mechanisms that maintain the virus. Here, we tracked HIV replication and the persistence of infected CD4 T cells in individuals with natural virologic control by sequencing viruses, T cell receptor genes, HIV integration sites, and cellular transcriptomes. Our results revealed three mechanisms of HIV persistence operating within distinct anatomic and functional compartments. In lymph node, we detected viruses with genetic and transcriptional attributes of active replication in both T follicular helper (TFH) cells and non-TFH memory cells. In blood, we detected inducible proviruses of archival origin among highly differentiated, clonally expanded cells. Linking the lymph node and blood was a small population of circulating cells harboring inducible proviruses of recent origin. Thus, HIV replication in lymphoid tissue, clonal expansion of infected cells, and recirculation of recently infected cells act together to maintain the virus in HIV controllers despite effective antiviral immunity.
Asunto(s)
Infecciones por VIH/virología , VIH-1/fisiología , Sangre/virología , Linfocitos T CD4-Positivos/inmunología , Enfermedad Crónica , ADN Viral/genética , Infecciones por VIH/inmunología , VIH-1/genética , Humanos , Leucocitos Mononucleares , Ganglios Linfáticos/virología , Provirus/inmunología , Análisis de Secuencia de ADN , Fenómenos Fisiológicos de los Virus , Replicación ViralRESUMEN
Invasive aspergillosis (IA) is an important opportunistic infection among patients with liver disease and liver transplants. Diagnosis of IA may be challenging, especially among patients with central nervous system infection. Herein, we demonstrate the utility of next-generation sequencing of microbial cell-free DNA in the diagnosis of fungal brain abscess in a liver transplant recipient.
Asunto(s)
Aspergilosis , Trasplante de Hígado , Neuroaspergilosis , Aspergilosis/diagnóstico , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Trasplante de Hígado/efectos adversos , Neuroaspergilosis/diagnóstico , Análisis de Secuencia de ADNRESUMEN
Tuberculosis (TB) causes approximately 2 million deaths annually worldwide, with 2 billion persons estimated to be actively infected with TB. While rates of active TB disease in the US military are low, military service in TB-endemic countries remains an uncommon, but important source of infection. United States Special Operations Forces (USSOF) and enablers often operate in TB-endemic countries and, as an inherent risk of their mission sets, are more likely to have high-risk exposure to TB disease. Military medical authorities have provided excellent diagnostic guidance; the Centers for Disease Control and Prevention (CDC) recently updated preferred regimens for the treatment of latent TB infection (LTBI). This review serves as a refresher and update to the management of LTBI in USSOF to optimize medical readiness through targeted testing and short treatment regimens.
Asunto(s)
Tuberculosis Latente , Personal Militar , Tuberculosis , Centers for Disease Control and Prevention, U.S. , Humanos , Tuberculosis Latente/diagnóstico , Tuberculosis Latente/tratamiento farmacológico , Tuberculosis Latente/epidemiología , Tuberculosis/diagnóstico , Tuberculosis/tratamiento farmacológico , Tuberculosis/epidemiología , Estados Unidos/epidemiologíaAsunto(s)
Catéteres de Permanencia , Cistitis/diagnóstico por imagen , Cistostomía , Enfisema/diagnóstico por imagen , Infecciones por Enterobacteriaceae/diagnóstico , Pielitis/diagnóstico por imagen , Anciano de 80 o más Años , Antibacterianos/uso terapéutico , Citrobacter , Cistitis/tratamiento farmacológico , Enterobacter cloacae , Infecciones por Enterobacteriaceae/tratamiento farmacológico , Humanos , Masculino , Hiperplasia Prostática/complicaciones , Pielitis/tratamiento farmacológico , Estrechez Uretral/complicaciones , Obstrucción del Cuello de la Vejiga Urinaria/etiología , Obstrucción del Cuello de la Vejiga Urinaria/terapia , Infecciones UrinariasRESUMEN
We studied the effects of a C60 water suspension at 4 microg/mL (nC60) and the water soluble fullerenol C60(OH)24 at final concentrations of 1-100 microg/mL on human umbilical vein endothelial cells (HUVECs) in culture. We found that a 24 hr treatment of HUVECs with C60(OH)24 at 100 microg/mL significantly increased cell surface expression of ICAM-1(CD54) (67 +/- 4% CD54+ cells vs. 19 +/- 2 % CD540 cells in control; p < 0.001). In addition, this treatment induced the expression of tissue factor (CD142) on HUVECs (54 +/- 20% CD142+ cells vs 4 +/- 2% CD142+ cells in control; p = 0.008) and increased exposure of phosphatidylserine (PS) (29 +/- 2% PS+ cells vs. 12 +/- 5% PS+ cells in control; p < 0.001). Analysis of cell cycle and DNA fragmentation (TUNEL) showed that both nC60 and C60(OH)24 caused G1 arrest of HUVECs and C60(OH)24 induced significant apoptosis (21 +/- 2% TUNEL+ cells at 100 microg/mL of C60(OH)24 vs. 4 +/- 2% TUNEL+ cells in control; p < 0.001). We also demonstrated that both nC60 and C60(OH)24 induced a rapid concentration dependent elevation of intracellular calcium [Ca2+]i. This could be inhibited by EGTA, suggesting that the source of [Ca2+]i in fullerene stimulated calcium flux is predominantly from the extracellular environment. In conclusion, fullerenol C60(OH)24 had both pro-inflammatory and pro-apoptotic effects on HUVECs, indicating possible adverse effects of fullerenes on the endothelium.