CCR5 blockers inhibit CCR5-tropic (R5) HIV-1, including strains resistant to other antiretrovirals. We demonstrate that the CCR5 antibody HGS004 and the CCR5 antagonist maraviroc have potent antiviral synergy against R5 HIV-1, translating into dose reductions of more than 10-fold for maraviroc and more than 150-fold for HGS004. These data, together with the high barrier of resistance to HGS004, suggest that combinations of maraviroc and HGS004 could provide effective preventive and therapeutic strategies against R5 HIV-1.
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http://dx.doi.org/10.1097/QAD.0b013e3283471edb | DOI Listing |
Front Immunol
January 2025
Laboratorio de Pediatria Clinica (LIM36), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil.
Introduction: Chemokines and their receptors are essential for leukocyte migration to several tissues, including human milk. Here, we evaluated the homing of T and B lymphocyte subsets to breast milk in response to ongoing respiratory infections in the nursing infant.
Methods: Blood and mature milk were collected from healthy mothers of nurslings with respiratory infections (Group I) and from healthy mothers of healthy nurslings (Group C).
J Biol Chem
January 2025
Department of Bioengineering, School of Engineering, The University of Tokyo; Institute of Medical Science, The University of Tokyo; Department of Chemistry and Biotechnology, School of Engineering, The University of Tokyo; Medical Device Development and Regulation Research Center, School of Engineering, The University of Tokyo, Japan. Electronic address:
Post-translational modification of proteins is a crucial biological reaction that regulates protein functions by altering molecular properties. The specific detection of such modifications in proteins has made significant contributions to molecular biology research and holds potential for future drug development applications. In HIV research, for example, tyrosine sulfation at the N-terminus of C-C chemokine receptor type 5 (CCR5) is considered to significantly enhance HIV infection efficiency.
View Article and Find Full Text PDFViruses
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 PDFToxicology
December 2024
Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing 100850, China. Electronic address:
Radon (Rn) is a naturally occurring radioactive gas, ionizing radiation emitted by the radon induces oxidative stress and the up-regulation of inflammatory proteins, which may cause lung damage or cancer. However, the underlying pathogenesis remains to be determined. Effector T helper cells are key in mediating the host's protection and immune homeostasis.
View Article and Find Full Text PDFVirology
December 2024
Section of Infectious Diseases, Department of Internal Medicine, Yale University, New Haven, CT, United States. Electronic address:
CCR5, a co-receptor critical for R5-tropic HIV entry into host cells, remains a key target for therapeutic interventions. HIV utilizes CCR5, expressed on T cells and macrophages, to facilitate viral entry. Genetic variants, such as the CCR5Δ32 homozygous mutation that confers protection to HIV infection, have made CCR5 a main target for gene-editing technologies, small-molecule inhibitors, and monoclonal antibody-based therapies.
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