Nef is one of the non-structural genes encoded by human immunodeficiency viruses. The protein product is associated with the cellular and plasma membranes, and is synthesized soon after entry of the virus. However, little is known about its functions relevant to viral replication and cytopathogenesis. CD4 is considered to be a crucial molecule for the signal transduction and maturation of T cells, and also serves as the receptor for HIV-1. It has been suggested that the down-regulation of cell surface CD4 by Nef proteins is somehow controversial. In order to evaluate the effects of Nef on the CD4 molecule, we constructed a CD4+ monocytoid cell line in which the HIV-1 nef gene was placed under the transcriptional control of the human metallothionein IIA promoter. The analysis of this cellular clone showed that CD4 on the cell surface was down-regulated when Nef proteins were induced. The amount of CD4 antigens on the cell surface correlated inversely with the level of Nef protein expression. This down-regulation of CD4 antigens by Nef was found to occur at the post-translational level. These results showed that the nef gene could modulate the pathophysiology of AIDS by altering the surface CD4 expression.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1093/intimm/5.9.1067 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Plasma anti-CD4 IgG levels are associated with poor immune recovery in people with HIV initiating antiretroviral therapy.
AIDS
February 2025
Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine, New York, NY.
A segment of people with HIV on effective antiretroviral therapy (ART) continue to experience poor immune recovery, leaving them at heightened risk of non-AIDS-defining events (NAEs). The production of anti-CD4 IgG autoreactive antibodies is suggested as one contributing mechanism to these complications. Here, we found that plasma anti-CD4 levels do not discriminate immunological responders from nonresponders nor predict the occurrence of NAEs, suggesting it is unlikely a contributing immunopathological factor associated with these complications.
View Article and Find Full Text PDFAdaptive ımmune system evaluation in familial mediterranean fever: clinical and ımmunological analysis.
Allergol Immunopathol (Madr)
January 2025
Faculty of Medicine, Department of Pediatric Allergy and Immunology, Ondokuz Mayıs University, Samsun, Turkey.
Background: Familial Mediterranean Fever is a common genetic autoinflammatory disease prevalent in the Mediterranean region. The clinical course of the disease is characterized by fever and serositis attacks. While defects in the innate immune system are known to play a role in the pathogenesis of the disease, the impact of the adaptive immune system remains unclear.
View Article and Find Full Text PDFEBV-specific T-cell immunity: relevance for multiple sclerosis.
Front Immunol
January 2025
Department of Neurology with Institute of Translational Neurology, University Hospital Münster, Münster, Germany.
Genetic and environmental factors jointly determine the susceptibility to develop multiple sclerosis (MS). Improvements in the design of epidemiological studies have helped to identify consistent environmental risk associations such as the increased susceptibility for MS following Epstein-Barr virus (EBV) infection, while biological mechanisms that drive the association between EBV and MS remain incompletely understood. An increased and broadened repertoire of antibody and T-cell immune responses to EBV-encoded antigens, especially to the dominant CD4 T-cell EBV nuclear antigen 1 (EBNA1), is consistently observed in patients with MS, indicating that protective EBV-specific immune responses are deregulated in MS and potentially contribute to disease development.
View Article and Find Full Text PDFAnti-CD4 monoclonal antibody prevents chronic graft-versus-host disease in mice by inducing immune tolerance of CD8 T cells and alleviating thymus injury.
Front Immunol
January 2025
Department of Hematology, Changhai Hospital, The Second Military Medical University, Shanghai, China.
Background: Chronic graft-versus-host disease (cGVHD) manifests with characteristics of autoimmune disease with organs attacked by pathogenic helper T cells. Recent studies have highlighted the role of T cells in cGVHD pathogenesis. Due to limited understanding of underlying mechanisms, preventing cGVHD after allogenic hematopoietic cell transplantation (HCT) has become a major challenge.
View Article and Find Full Text PDFAnti-Inflammatory Effects of Clarstatin, a Shared-Epitope-Antagonistic Cyclic Peptide, on Experimental Autoimmune Uveitis in Mice.
Invest Ophthalmol Vis Sci
January 2025
Department of Ophthalmology, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.
Purpose: Polymorphism and mutations of human leukocyte antigens (HLAs) and calreticulin are risk factors for uveitis. Here, we sought to determine the therapeutic effects of Clarstatin, a cyclic peptide antagonist of the HLA shared-epitope-calreticulin interaction, in experimental autoimmune uveitis (EAU) models.
Methods: Mice were injected with Clarstatin intraperitoneally and its effect was compared to that of corticosteroid.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!