Background: Human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) is a major target for antiretroviral strategy to block or curtail HIV infection. A suitable RT-SHIV/macaque model is urgently needed for the evaluation of HIV/AIDS therapies and microbicides specifically targeting HIV-1 RT.
Methods: Fifteen cynomolgus macaques (Macaca fascicularis) were divided into three groups (n = 5) and intravaginally inoculated with 4800, 1200, or 300 TCID(50) of RT-SHIVtc. Systemic infections of RT-SHIVtc exposed macaques were determined by both virological and immunologic parameters during 24 weeks post-challenge.
Results: Within 2 weeks post-inoculation, 13 of 15 macaques became infected as confirmed by virus isolation, plasma viral RNA, proviral DNA, declined CD4(+)T cell counts in peripheral blood and seroconversion.
Conclusions: Results serve to validate the infectivity and pathogenicity of RT-SHIVtc following vaginal exposure in M. fascicularis. This RT-SHIVtc/macaque model could be suitable for the pre-clinical evaluation of non-nucleoside RT inhibitor-based anti-HIV microbicides.
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http://dx.doi.org/10.1111/j.1600-0684.2009.00374.x | DOI Listing |
Transl Vis Sci Technol
January 2025
STZ eyetrial at the Centre for Ophthalmology, Tuebingen, Germany.
Purpose: Reports of gene therapy-associated retinal atrophies and inflammation have highlighted the importance of preclinical safety assessments of adeno-associated virus (AAV) vector systems. We evaluated in nonhuman primates (NHPs) the ocular safety and toxicology of a novel AAV gene therapy targeting retinitis pigmentosa caused by mutations in PDE6A, which has since been used in a phase I/II clinical trial (NCT04611503).
Methods: A total of 34 healthy cynomolgus animals (Macaca fascicularis) were treated with subretinal injections of rAAV.
Heliyon
January 2025
Guangdong Provincial Biotechnology Research Institute (Guangdong Provincial Laboratory Animals Monitoring Center), Guangzhou, Guangdong, 510663, China.
Spondyloarthritis is a prevalent and persistent condition that significantly impacts the quality of life. Its intricate pathological mechanisms have led to a scarcity of animal models capable of replicating the disease progression in humans, making it a prominent area of research interest in the field. To delve into the pathological and physiological traits of spontaneous non-human primate spondyloarthritis, this study meticulously examined the disease features of this natural disease model through an array of techniques including X-ray imaging, MRI imaging, blood biochemistry, markers of bone metabolism, transcriptomics, proteomics, and metabolomics.
View Article and Find Full Text PDFBirth Defects Res
February 2025
Translational Research Division, Chugai Pharmaceutical Co. Ltd., Chuo, Japan.
Background: Nemolizumab, a humanized monoclonal antibody against interleukin-31 receptor A (IL-31RA), is used to treat atopic dermatitis and prurigo nodularis. These inflammatory skin diseases affect a wide range of age groups, including pregnant women and children; however, little is known about their biological effects on pre- and postnatal development. Therefore, we report and discuss the results of an enhanced pre- and postnatal development study in cynomolgus monkeys treated with nemolizumab, which also incorporates an assessment of juvenile toxicities.
View Article and Find Full Text PDFMicroorganisms
January 2025
Department of Psychology, University of Houston, Houston, TX 77004, USA.
Social housing changes are likely stressful and can be associated with diarrhea, the most common health problem noted in captive macaque populations. Diarrhea may reflect a negative shift in the gut flora ("gut dysbiosis"). This study reported on changes in the gut microbiome composition of juvenile primates () that experienced a change in social housing and exhibited diarrhea.
View Article and Find Full Text PDFInt J Pharm
January 2025
Université Paris-Saclay, Inserm, Maladies et hormones du système nerveux, 94276 Le Kremlin-Bicêtre, France. Electronic address:
Small interfering RNA (siRNA) has shown promising results for the treatment of Charcot-Marie-Tooth disease 1A (CMT1A) caused by overexpression of peripheral myelin protein (PMP22), leading to myelin dysfunction and axonal damage. Recently, we developed siRNA PMP22-squalene (SQ) nanoparticles (NPs) for intravenous use. Three consecutive injections of siRNA PMP22-SQ NPs at a cumulative dose of 1.
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