Purpose Of Review: Elite controllers constitute a rare group of HIV-infected individuals who control HIV replication and maintain normal CD4 cell counts without antiretroviral therapy (ART). The mechanisms involved in the control of infection are poorly understood. This review will focus on the identification of signaling pathways upregulated or downregulated in different memory T-cell subsets in elite controllers by using systems biology approaches. Features of memory T cells in simian immunodeficiency virus (SIV) natural hosts will be also highlighted. Finally, we will discuss how these approaches will guide the development of new vaccines and therapeutic interventions.
Recent Findings: Studies by our group identified the FOXO3a, STAT5, and Wnt/beta-catenin pathways as unique molecular signatures associated with survival of memory T cells in elite controllers. These discoveries open the path for the design of new strategies to prevent T-cell depletion in HIV-infected individuals.
Summary: The use of systems biology to identify molecular pathways involved in the survival of memory T cells is a powerful tool toward the understanding of mechanisms of HIV control in elite controllers. This will help to identify correlates of immune protection leading to the design of effective HIV vaccines and new targeted therapeutic interventions.
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http://dx.doi.org/10.1097/COH.0b013e32834589a1 | DOI Listing |
Curr Opin HIV AIDS
December 2024
Institute of Biomedicine of Seville (IBiS), Virgen del Rocio University Hospital, Spanish National Research Council (CSIC), University of Seville, Clinical Unit of Infectious Diseases, Microbiology and Parasitology, Seville, Spain.
Purpose Of Review: To summarize the heterogeneity in the elite controllers population with the aim to identify a compatible profile with a persistent HIV remission, making distinction between persistent elite controllers, people with HIV (PWHIV) who permanently maintain virological control in the absence of antiretroviral treatment (ART), and transient elite controllers, PWHIV who eventually lose virological control. For this purpose, it is important to consider the mechanisms and biomarkers that have previously been associated with the maintenance and loss of the natural virological control.
Recent Findings: Transient elite controllers, before losing virological control, exhibit a distinct metabolomic, proteomic, microRNAs (miRNA), immunological and virological profile compared to persistent elite controllers.
BMC Immunol
January 2025
Laboratoire Génomique, Bioinformatique, et Chimie Moléculaire, Conservatoire National des Arts et Métiers, 2 rue Conté 75003, Paris, EA7528, France.
Introduction: We have reanalyzed the genomic data from the International Collaboration for the Genomics of HIV (ICGH), focusing on HIV-1 Elite Controllers (EC).
Methods: A genome-wide association study (GWAS) was performed, comparing 543 HIV-1 EC individuals with 3,272 uninfected controls (CTR) of European ancestry. 8 million single nucleotide polymorphisms (SNPs) and HLA class I and class II gene alleles were imputed to compare EC and CTR.
Epigenetics Chromatin
January 2025
Department of Biomedical Sciences, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Kepala Batas, Penang, Malaysia.
Despite significant advances in HIV treatment, a definitive cure remains elusive. The first-in-human clinical trial of Excision BioTherapeutics' CRISPR-based HIV cure, EBT-101, demonstrated safety but failed to prevent viral rebound. These outcomes may result from the interplay of several factors.
View Article and Find Full Text PDFCurr HIV/AIDS Rep
November 2024
Department of Internal Medicine and Infectious Diseases, Radboud University Medical Center, Geert Grooteplein Zuid 8, 6525 GA, Nijmegen, The Netherlands.
Purpose Of Review: To review the role of innate immune cells in shaping the viral reservoir and maintenance of long-term viral control of spontaneous Elite and Viremic HIV controllers.
Recent Findings: HIV controllers exhibit a smaller and transcriptionally suppressed viral reservoir. Different studies report that early responses from innate cells play a pivotal role in this reservoir configuration.
iScience
November 2024
Quantitative Virology Research Group, Population Diagnostics Center, Łukasiewicz Research Network - PORT Polish Center for Technology Development, Stabłowicka 147, 54-066 Wrocław, Poland.
HIV-1 reservoirs display a heterogeneous nature, lodging both intact and defective proviruses. To deepen our understanding of such heterogeneous HIV-1 reservoirs and their functional implications, we integrated basic concepts of graph theory to characterize the composition of HIV-1 reservoirs. Our analysis revealed noticeable topological properties in networks, featuring immunologic signatures enriched by genes harboring intact and defective proviruses, when comparing antiretroviral therapy (ART)-treated HIV-1-infected individuals and elite controllers.
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