التفاصيل البيبلوغرافية
| العنوان: |
Direct interaction of HIV gp120 with neuronal CXCR4 and CCR5 receptors induces cofilin-actin rod pathology via a cellular prion protein- and NOX-dependent mechanism |
| المؤلفون: |
Smith, Lisa K., Babcock, Isaac W., Minamide, Laurie S., Shaw, Alisa E., Bamburg, James R., Kuhn, Thomas B. |
| المساهمون: |
Wu, Yuntao, National Institute on Aging, National Institutes of Health, National Institute of Neurological Disorders and Stroke, National Institute of General Medical Sciences, Colorado State University Microscopy Imaging Core, Alzheimer’s Research Foundation of Alaska |
| المصدر: |
PLOS ONE ; volume 16, issue 3, page e0248309 ; ISSN 1932-6203 |
| بيانات النشر: |
Public Library of Science (PLoS) |
| سنة النشر: |
2021 |
| المجموعة: |
PLOS Publications (via CrossRef) |
| الوصف: |
Nearly 50% of individuals with long-term HIV infection are affected by the onset of progressive HIV-associated neurocognitive disorders (HAND). HIV infiltrates the central nervous system (CNS) early during primary infection where it establishes persistent infection in microglia (resident macrophages) and astrocytes that in turn release inflammatory cytokines, small neurotoxic mediators, and viral proteins. While the molecular mechanisms underlying pathology in HAND remain poorly understood, synaptodendritic damage has emerged as a hallmark of HIV infection of the CNS. Here, we report that the HIV viral envelope glycoprotein gp120 induces the formation of aberrant, rod-shaped cofilin-actin inclusions (rods) in cultured mouse hippocampal neurons via a signaling pathway common to other neurodegenerative stimuli including oligomeric, soluble amyloid-β and proinflammatory cytokines. Previous studies showed that synaptic function is impaired preferentially in the distal proximity of rods within dendrites. Our studies demonstrate gp120 binding to either chemokine co-receptor CCR5 or CXCR4 is capable of inducing rod formation, and signaling through this pathway requires active NADPH oxidase presumably through the formation of superoxide (O 2- ) and the expression of cellular prion protein (PrP C ). These findings link gp120-mediated oxidative stress to the generation of rods, which may underlie early synaptic dysfunction observed in HAND. |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
English |
| DOI: |
10.1371/journal.pone.0248309 |
| الإتاحة: |
https://doi.org/10.1371/journal.pone.0248309Test |
| حقوق: |
http://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: |
edsbas.447E3EFD |
| قاعدة البيانات: |
BASE |
