Objectives: SAMHD1 and the CDKN1A (p21) cyclin-dependent kinase inhibitor have been postulated to mediate HIV-1 restriction in CD4+ cells. We have shown that p21 affects HIV replication through its effect on SAMHD1. Thus, we aimed at evaluating the expression of SAMHD1 and p21 in different HIV+ phenotypic groups.
Patients And Methods: We evaluated SAMHD1 and CDKN1A mRNA expression in CD4+ T cells from HIV+ individuals including elite controllers (n = 12), individuals who control HIV without the need for antiretroviral treatment, viraemic progressors (n = 10) and HIV-1 seronegative healthy donors (n = 14). Immunological variables were measured by flow cytometry.
Results: We show that a subset of HIV+ elite controllers with lower T cell proliferation levels (Ki67+ cells) expressed higher SAMHD1 compared with healthy donors or viraemic progressors. Conversely, there was no difference in p21 expression before or after T cell activation with a bispecific CD3/CD8 antibody.
Conclusions: Our results suggest that SAMHD1 may play a role in controlling virus replication in HIV+ individuals and slow the rate of disease progression.
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http://dx.doi.org/10.1093/jac/dku276 | DOI Listing |
Curr 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.
View Article and Find Full Text PDFFront Immunol
September 2024
Department of Medicine, Case Western Reserve University, Cleveland, OH, United States.
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