Magnetic resonance spectroscopy reveals that activated monocytes contribute to neuronal injury in SIV neuroAIDS
Year: 2005
Type: article
Abstract: Difficulties in understanding the mechanisms of HIV neuropathogenesis include the inability to study dynamic processes of infection, cumulative effects of the virus, and contributing host immune responses. We used H magnetic resonance spectroscopy and studied monocyte activation and progression of CNS neuronal injury in a CD8 lymphocyte depletion model of neuroAIDS in SIV-infected rhesus macaque monkeys. We found early, consistent neuronal injury coincident with viremia and SIV infection/activation of monocyte subsets and sought to define the role of plasma virus and monocytes in contributing to CNS disease. Antiretroviral therapy with essentially non-CNS-penetrating agents resulted in slightly decreased levels of plasma virus, a significant reduction in the number of activated and infected monocytes, and rapid, near-complete reversal of neuronal injury. Robust macrophage accumulation and productive virus replication were found in brains of infected and CD8 lymphocyte-depleted animals, but no detectable virus and few scattered infiltrating macrophages were observed in CD8 lymphocyte-depleted animals compared with animals not receiving antiretroviruses that were sacrificed at the same time after infection. These results underscore the role of activated monocytes and monocyte infection outside of the brain in driving CNS disease.
DOI: 10.1172/jci22953
Institutions: Beth Israel Deaconess Medical Center, Harvard University, Massachusetts General Hospital, Athinoula A. Martinos Center for Biomedical Imaging, Emory University, Atlanta VA Medical Center, Gilead Sciences (United States), National Cancer Institute, Science Applications International Corporation (United States), University of California San Diego
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: bronze
Funders: U.S. Department of Veterans Affairs, Massachusetts General Hospital, Emory University, National Institutes of Health, Center for AIDS Research, University of Washington, National Institute of Mental Health, National Institute of Allergy and Infectious Diseases, National Institute of Neurological Disorders and Stroke, National Center for Research Resources
Awards: G1579668542, G1717234197, G1947016736, Resource for Nonhuman Primate Cell Depleting Antibodies, G2637518854, G3582068888, G401230023, CHEMOKINE RECEPTORS AND SIV NEUROPATHOGENESIS, Monocyte Traffic and Neuropathogenesis of AIDS, MR Spectroscopy of SIV Brain Injury, Center for Functional Imaging Technologies, MOUSE MODELS OF CANCER, BONE DISEASE, AND LACTATION, G7021969697, HIV NEUROBEHAVIORAL RESEARCH CENTER, MOLECULAR NEUROIMAGING OF AIDS DEMENTIA--ANIMAL MODELS, G8794105464, G9000074708, G9000106381, New England Primate Research Center Base Grant, G9000296683, Center for AIDS Research at Emory University
OpenAlex ID: W2115316421