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Exploitation of Unconventional CD8 T-Cell Responses Induced by Engineered Cytomegaloviruses for the Development of an HIV-1 Vaccine.
Vaccines (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 PDFViremic non-progression in HIV/SIV infection: A tied game between virus and host.
Cell 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 PDFTransformation of brain myeloid cell populations by SIV in rhesus macaques revealed by multiomics.
Commun Biol
January 2025
Department of Neurological Sciences, University of Nebraska Medical Center, Omaha, NE, USA.
The primary immune constituents in the brain, microglia and macrophages, are the target for HIV in people and simian immunodeficiency virus (SIV) in nonhuman primates. This infection can lead to neurological dysfunction, known as HIV-associated neurocognitive disorder (HAND). Given the gaps in our knowledge on how these cells respond in vivo to CNS infection, we perform single-cell multiomic sequencing, including gene expression and ATAC-seq, on myeloid cells from the brains of rhesus macaques with SIV-induced encephalitis (SIVE) as well as uninfected controls.
View Article and Find Full Text PDFHIV-1 Vpu and SARS-CoV-2 ORF3a proteins disrupt STING-mediated activation of antiviral NF-κB signaling.
Sci Signal
January 2025
Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310000, China.
Activation of the stimulator of interferon genes (STING) pathway by cytosolic DNA leads to the activation of the transcription factors interferon regulatory factor 3 (IRF3) and nuclear factor κB (NF-κB). Although many viruses produce proteins that inhibit IRF3-dependent antiviral responses, some viruses produce proteins that inhibit STING-induced NF-κB activation without blocking IRF3 activation. Here, we found that STING-activated, NF-κB-dependent, and IRF3-independent innate immunity inhibited the replication of the DNA virus herpes simplex virus type 1 (HSV-1), the RNA virus coxsackievirus A16 (CV-A16), and the retrovirus HIV-1.
View Article and Find Full Text PDFPlasma galectin-9 levels correlate with blood monocyte turnover and predict simian/human immunodeficiency virus disease progression.
Transl Med Commun
January 2024
Department of Anatomy, Physiology, & Cell Biology, School of Veterinary Medicine, and California National Primate Research Center, University of California, Davis, County Road 98 & Hutchison Drive, Davis, CA, USA.
Background: Late-stage human immunodeficiency virus (HIV) infection is typically characterized by low CD4 + T-cell count. We previously showed that profound changes in the monocyte turnover (MTO) rate in rhesus macaques infected by the simian immunodeficiency virus (SIV) outperforms declining CD4 + T-cell counts in predicting rapid health decline associated with progression to terminal disease. High MTO is associated with increased tissue macrophage death.
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