During chronic human immunodeficiency virus (HIV) infection, virus-specific CD8(+) T cells become functionally exhausted. Unlike most chronically infected individuals, elite controllers of HIV retain CD8(+) T-cell polyfunctionality and cytolytic capacity. It remains unclear whether elite controllers manifest T-cell exhaustion similar to subjects with chronic progression of HIV infection. Here we assessed coexpression of PD-1, Lag-3, CD160, and 2B4 as a measure of T-cell exhaustion in a cohort of elite controllers and in chronic progressors. We found that elite controllers have a high proportion of potentially exhausted (PD1(+)CD160(+)2B4(+)) HIV-specific CD8(+) T cells that is comparable to the proportion in chronic progressors. However, elite controllers also harbor a population of HIV-specific CD160(+)2B4(+) CD8(+) T cells that correlates with cytolytic capacity, as measured by perforin expression, a population not commonly present in chronic progressors. We therefore propose that coexpression of CD160 and 2B4 delineates a population of cytolytic CD8(+) T cells important for the control of HIV.
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http://dx.doi.org/10.1093/infdis/jiv226 | DOI Listing |
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.
View Article and Find Full Text PDFRetrovirology
October 2024
Department of Pediatrics, Weill Cornell Medicine, New York, NY, 10021, USA.
Despite the efficacy of antiretroviral therapy (ART) in reducing the global incidence of vertical HIV transmissions, more than 120,000 children are still infected with the virus each year. Since ART cannot clear the HIV reservoir that is established soon after infection, children living with HIV (CLWH) are forced to rely on therapy for their lives and suffer from long-term drug-related complications. Pediatric HIV infection, like adult infection, is associated with gut microbial dysbiosis, loss of gut epithelial integrity, bacterial translocation, CD4 + T cell depletion, systemic immune activation, and viral reservoir establishment.
View Article and Find Full Text PDFJCI Insight
September 2024
Infectious Diseases Department, Hospital Universitari Vall d'Hebron, Institut de Recerca (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain.
Elite controllers (ECs), a unique group of people with HIV (PWH), exhibit remarkable control of viral replication in the absence of antiretroviral therapy. In this study, we comprehensively characterized the NK cell repertoire in ECs after long-term viral control. Phenotypic profiling of NK cells revealed profound differences compared with other PWH, but marked similarities to uninfected individuals, with a distinctive prevalence of NKG2C+CD57+ memory-like NK cells.
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