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A simple phylogenetic approach to analyze hypermutated HIV proviruses reveals insights into their dynamics and persistence during antiretroviral therapy.
Virus Evol
November 2024
Faculty of Health Sciences, Simon Fraser University, 8888 University Drive, Burnaby, BC V5A 1S6, Canada.
Hypermutated proviruses, which arise in a single Human Immunodeficiency Virus (HIV) replication cycle when host antiviral APOBEC3 proteins introduce extensive guanine to adenine mutations throughout the viral genome, persist in all people living with HIV receiving antiretroviral therapy (ART). However, hypermutated sequences are routinely excluded from phylogenetic trees because their extensive mutations complicate phylogenetic inference, and as a result, we know relatively little about their within-host evolutionary origins and dynamics. Using >1400 longitudinal single-genome-amplified HIV sequences isolated from six women over a median of 18 years of follow-up-including plasma HIV RNA sequences collected over a median of 9 years between seroconversion and ART initiation, and >500 proviruses isolated over a median of 9 years on ART-we evaluated three approaches for masking hypermutation in nucleotide alignments.
View Article and Find Full Text PDFReactive molecular dynamics simulations investigating ROS-mediated HIV damage from outer gp120 protein to internal capsid protein.
RSC Adv
January 2025
Xinjiang Laboratory of Phase Transitions and Microstructures in Condensed Matter Physics, College of Physical Science and Technology, Yili Normal University Yining 835000 China
Molecular dynamics (MD) with the ReaxFF force field is used to study the structural damage to HIV capsid protein and gp120 protein mediated by reactive oxygen species (ROS). Our results show that with an increase in ROS concentration, the structures of the HIV capsid protein and gp120 protein are more severely damaged, including dehydrogenation, increase in oxygen-containing groups, helix shortening or destruction, and peptide bond breaking. In particular, we noticed that extraction of H atoms from N atoms by ROS was significantly higher than that from C atoms.
View Article and Find Full Text PDFPKR Inhibitor C16 Regulates HIV-gp120 Induced Neuronal Injury and Cognitive Impairment in Vivo and in Vitro Models.
Neurochem Res
January 2025
College of Pharmacy, Guangxi Medical University, Guangxi Zhuang Autonomous Region, Nanning, 530021, China.
To study the neuronal protective effect and its potential mechanism of C16 against gp120-induced cognitive impairment in vitro and in vivo. The NORT method was used to evaluate the short-term memory abilities of rats, the morphological changes in hippocampus were observed by Nissl staining. Cell viability and damage degree were detected by MTT and LDH.
View Article and Find Full Text PDFp62 Binding to Protein Kinase C Regulates HIV-1 gp120 V3 Loop Induced Microglial Inflammation.
Inflammation
December 2024
Department of Pathophysiology, Key Laboratory of the State Administration of Traditional Chinese Medicine, Medical College of Jinan University, Guangzhou, Guangdong Province, China.
The main pathogenic mechanism of HIV-associated neurocognitive disorders (HAND) is neuronal apoptosis induced by inflammatory mediators, in which microglial inflammation plays a crucial role. However, the exact pathogenic mechanism remains unclear. Previous studies have shown that the HIV-1 gp120 V3 loop can trigger inflammation in CHME-5 microglia.
View Article and Find Full Text PDFTwo Disaccharide-Bearing Polyethers, K-41B and K-41Bm, Potently Inhibit HIV-1 via Mechanisms Different from That of Their Precursor Polyether, K-41A.
Curr Issues Mol Biol
November 2024
Guangxi Key Laboratory of AIDS Prevention and Treatment, School of Public Health, Guangxi Medical University, Nanning 530021, China.
The screening of novel antiviral agents from marine microorganisms is an important strategy for new drug development. Our previous study found that polyether K-41A and its analog K-41Am, derived from a marine Streptomyces strain, exhibit anti-HIV activity by suppressing the activities of HIV-1 reverse transcriptase (RT) and its integrase (IN). Among the K-41A derivatives, two disaccharide-bearing polyethers-K-41B and K-41Bm-were found to have potent anti-HIV-1 activity in vitro.
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