Despite multiple exposures to HIV-1, some individuals remain uninfected. This resistance to HIV infection has been associated with homozygosity for a 32-basepair deletion in the CCR5 receptor gene. This variant is frequent in caucasians but extremely rare in Asians and Africans. Identifying variations in the CCR5 gene that affect susceptibility to HIV infection in non-caucasians is therefore of great interest. In this report, we identify 5 CCR5 coding region variants in a Chinese population. The K26R mutation is an undescribed gene variant, whereas 228delK was already found in caucasians and G106R, C178R, and R223Q were previously described in Asian populations and functionally analyzed. As the function of K26R was still unknown, we focused our work on studying its chemokine receptor activity and HIV coreceptor properties compared with wild-type CCR5 and G106R, an already analyzed mutant taken as another control. We observed that K26R displayed alteration in MIP1-beta/CCL4 and RANTES/CCL5 ligand binding and exhibited a slightly decrease for HIV coreceptor properties.
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http://dx.doi.org/10.1097/01.qai.0000158761.71165.e9 | DOI Listing |
Viruses
November 2024
Department of Virology & Biotechnology, ICMR-National Institute for Research in Tuberculosis, Chennai 600031, India.
The biological characteristics of early transmitted/founder (T/F) variants are crucial factors for viral transmission and constitute key determinants for the development of better therapeutics and vaccine strategies. The present study aimed to generate T/F viruses and to characterize their biological properties. For this purpose, we constructed 18 full-length infectious molecular clones (IMCs) of HIV from recently infected infants.
View Article and Find Full Text PDFSci Rep
January 2025
Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA, 52242, USA.
α-Klotho (KLA) is a type-1 membranous protein that can associate with fibroblast growth factor receptor (FGFR) to form co-receptor for FGF23. The ectodomain of unassociated KLA is shed as soluble KLA (sKLA) to exert FGFR/FGF23-independent pleiotropic functions. The previously determined X-ray crystal structure of the extracellular region of sKLA in complex with FGF23 and FGFR1c suggests that sKLA functions solely as an on-demand coreceptor for FGF23.
View Article and Find Full Text PDFPathol Res Pract
December 2024
Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Sydney, NSW 2007, Australia; Faculty of Health, Australian Research Consortium in Complementary and Integrative Medicine, University of Technology Sydney, Ultimo, Australia. Electronic address:
Chronic inflammatory conditions, which include respiratory diseases and other ailments, are characterized by persistent inflammation and oxidative stress, and represent a significant health burden, often inadequately managed by current therapies which include conventional inhaled bronchodilators and oral or inhaled corticosteroids in the case of respiratory disorders. The present study explores the potential of Vedicinals®9 Advanced, a polyherbal formulation, to mitigate LPS-induced inflammation and oxidative stress in RAW264.7 mouse macrophages.
View Article and Find Full Text PDFMol Ther
December 2024
Department of Immunology and Microbiology, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation and Technology, Jupiter, FL 33458, USA. Electronic address:
eCD4-immunoglobulin (Ig) is an HIV entry inhibitor that mimics the engagement of both CD4 and CCR5 with the HIV envelope (Env) protein, a property that imbues it with remarkable potency and breadth. However, env is exceptionally genetically malleable and can evolve to escape a wide variety of entry inhibitors. Here we document the evolution of partial eCD4-Ig resistance in SHIV-AD8-infected rhesus macaques (RMs) treated with adeno-associated virus vectors encoding eCD4-Ig.
View Article and Find Full Text PDFCytokine
January 2025
Department of Medical Biotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran; Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran. Electronic address:
Background: To overcome the limitations of IL-15 and to improve the efficacy of IL-15 in immunotherapy, several strategies have been introduced.
Objective: The objective of this study was to generate and evaluate a novel anti-CD8/IL-15 (N72D)/Sushi fusion protein with the potential to target CD8 T cells and enhance functionality of CD8 T cells against tumor cells.
Methods: In this connection, a novel fusokine that contains IL-15(N72D), a Sushi domain, and anti-CD8 single-chain fragment variable (scFv) was designed.
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