Nef of primate lentiviruses is required for viremia and progression to AIDS in monkeys. Negative, positive, and no effects of Nef have also been reported on viral replication in cells. To reconcile these observations, we expressed a hybrid CD8-Nef protein in Jurkat cells. Two opposite phenotypes were found, which depended on the intracellular localization of Nef. Expressed in the cytoplasm or on the cell surface, the chimera inhibited or activated early signaling events from the T cell antigen receptor. Activated Jurkat cells died by apoptosis, and only cells with mutated nef genes expressing truncated Nefs survived, which rendered Nef nonfunctional. These mutations paralleled those in other viral strains passaged in vitro. Not only do these positional effects of Nef reconcile diverse phenotypes of Nef and suggest a role for its N-terminal myristylation, but they also explain effects of Nef in HIV infection and progression to AIDS.
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http://dx.doi.org/10.1016/1074-7613(94)90068-x | DOI Listing |
Pharmaceuticals (Basel)
January 2025
Department of Basic Sciences, Ponce Research Institute, Ponce Health Sciences University, Ponce, PR 00716, USA.
Background/objectives: Cocaine use disorder is an intersecting issue in populations with HIV-1, further exacerbating the clinical course of the disease and contributing to neurotoxicity and neuroinflammation. Cocaine and HIV neurotoxins play roles in neuronal damage during neuroHIV progression by disrupting glutamate homeostasis in the brain. Even with combined antiretroviral therapy (cART), HIV-1 Nef, an early viral protein expressed in approximately 1% of infected astrocytes, remains a key neurotoxin.
View Article and Find Full Text PDFRev Med Chil
November 2024
Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
In the prevailing medical pluralism of contemporary society, alternative and complementary medicine occupy a relevant place, comprising a heterogeneous group of practices with different values depending on tradition and social acceptance. Their scarce regulation and growing use, facilitated by promotion through social networks and distrust of the dominant biomedical model, have generated interest among medical organizations and health authorities in their use and consequences. Appreciations vary from outright rejection to interest in its adoption by public health systems as part of their services.
View Article and Find Full Text PDFBMC Neurol
January 2025
Department of Neurology, University Hospital Bern, Inselspital, University of Bern, Bern, Switzerland.
Background: Effects of subthalamic nucleus deep brain stimulation (STN-DBS) on neuropsychiatric symptoms of Parkinson's disease (PD) remain debated. Sensor technology might help to objectively assess behavioural changes after STN-DBS.
Case Presentation: 5 PD patients were assessed 1 before and 5 months after STN-DBS with the Movement Disorders Society Unified Parkinson's Disease Rating Scale part III in the medication ON (plus postoperatively stimulation ON) condition, the Montreal Cognitive Assessment, the Questionnaire for Impulsive-Compulsive Behaviors in Parkinson's Disease Rating Scale present version, the Hospital Anxiety and Depression Scale and the Starkstein Apathy Scale.
EMBO Rep
January 2025
The Zhongzhou Laboratory for Integrative Biology, Henan University, 450000, Zhengzhou, Henan, China.
Although females typically have a survival advantage, those with PTEN functional abnormalities face a higher risk of developing tumors than males. However, the differences in how each sex responds to PTEN dysfunction have rarely been studied. We use Caenorhabditis elegans to investigate how male and hermaphrodite worms respond to dysfunction of the PTEN homolog daf-18.
View Article and Find Full Text PDFViruses
November 2024
Departments of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
HIV-1 subtype C viruses are responsible for 50% of global HIV burden. However, nearly all currently available reporter viruses widely used in HIV research are based on subtype B. We constructed and characterized a replication-competent HIV-1 subtype C reporter virus expressing mGreenLantern.
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