Lentiviruses have a long-documented association with macrophages. Abundant evidence exists for in vitro and, in a tissue-specific manner, in vivo infection of macrophages by the primate lentiviruses HIV-1 and SIV. However, macrophage contribution to aspects of HIV-1 and SIV pathogenesis, and their role in viral persistence in individuals on suppressive antiretroviral therapy, remains unclear. Here we discuss recent evidence implicating macrophages in HIV-1-mediated disease and highlight directions for further investigation.
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http://dx.doi.org/10.1016/j.chom.2016.02.013 | DOI Listing |
Int J Mol Sci
January 2025
MRL, Merck & Co., Inc., Rahway, NJ 07065, USA.
Despite the success of combination antiretroviral therapy (cART) to suppress HIV replication, HIV persists in a long-lived reservoir that can give rise to rebounding viremia upon cART cessation. The translationally active reservoir consists of HIV-infected cells that continue to produce viral proteins even in the presence of cART. These active reservoir cells are implicated in the resultant viremia upon cART cessation and likely contribute to chronic immune activation in people living with HIV (PLWH) on cART.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
Clinic of Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany.
The peptidyl-prolyl isomerase A (PPIA), also known as cyclophilin A (CYPA), is involved in multiple steps of the HIV-1 replication cycle. CYPA regulates the restriction of many host factors by interacting with the CYPA-binding loop on the HIV-1 capsid (CA) surface. TRIM5 (tripartite motif protein 5) in primates is a key species-specific restriction factor defining the HIV-1 pandemic.
View Article and Find Full Text PDFVaccines (Basel)
January 2025
The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7DQ, UK.
After four decades of intensive research, traditional vaccination strategies for HIV-1 remain ineffective due to HIV-1's extraordinary genetic diversity and complex immune evasion mechanisms. Cytomegaloviruses (CMV) have emerged as a novel type of vaccine vector with unique advantages due to CMV persistence and immunogenicity. Rhesus macaques vaccinated with molecular clone 68-1 of RhCMV (RhCMV68-1) engineered to express simian immunodeficiency virus (SIV) immunogens elicited an unconventional major histocompatibility complex class Ib allele E (MHC-E)-restricted CD8 T-cell response, which consistently protected over half of the animals against a highly pathogenic SIV challenge.
View Article and Find Full Text PDFCell Rep Med
January 2025
IrsiCaixa Immunopathology Research Institute, Badalona, Spain; Germans Trias i Pujol Research Institute, Badalona, Spain; CIBERINFEC, Institute of Health Carlos III, Madrid, Spain. Electronic address:
High-efficacy antiretroviral treatment (ART) has been a game-changer for HIV/AIDS pandemic, but incomplete CD4 T cell recovery and persistent chronic immune activation still affect HIV-suppressed people. Exceptional cases of HIV infection that naturally exhibit delayed disease progression provide invaluable insights into protective biological mechanisms with potential clinical application. Viremic non-progressors (VNPs) represent an extremely rare population of individuals with HIV, characterized by preservation of the CD4 T cell compartment despite persistent high levels of viral load (>10,000 copies/mL).
View Article and Find Full Text PDFCell Rep
January 2025
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address:
The membrane-proximal external region (MPER) of the HIV-1 envelope is a target for broadly neutralizing antibodies (bnAbs), and vaccine-elicited MPER-directed antibodies have recently been reported from a human clinical trial. In this study, we sought to identify MPER-directed nAbs in simian immunodeficiency virus (SIV)-infected rhesus macaques. We isolated four lineages of SIV MPER-directed nAbs from two SIV-infected macaques.
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