Dorsal root ganglia damage in SIV-infected rhesus macaques: an animal model of HIV-induced sensory neuropathy.
HIV-associated sensory neuropathy (HIV-SN) is currently the most common neurological complication of chronic HIV infection and continues to substantially affect patient quality of life. Mechanisms underlying the neuronal damage and loss observed in sensory ganglia of HIV-infected individuals have not been sufficiently studied. The present study aimed to develop and characterize a model of HIV-SN using SIV-infected CD8 T-lymphocyte-depleted rhesus macaques (Macaca mulatta). Uninfected controls (n = 5), SIV-infected CD8-depleted (n = 4), and SIV-infected non-CD8-depleted (n = 6) animals were used. Of the six non-CD8-depleted animals, three were conventional progressors (progressing to AIDS >1 year after infection) and three were rapid progressors (AIDS within 6 months). Dorsal root ganglia (DRG) were examined for histological hallmarks of HIV-SN, including satellitosis, presence of Nageotte nodules, and neuronophagia, as well as increased numbers of CD68(+) macrophages and abundant viral replication. In contrast to non-CD8-depleted animals, which had mild to moderate DRG pathology, the CD8-depleted SIV-infected animals had moderate to severe DRG damage, with increased numbers of CD68(+) satellite cells. Additionally, there was marked active viral replication in the affected DRG. These findings confirm that many features of HIV-SN can be recapitulated in the CD8-depleted SIV-infected rhesus macaque model within a short time frame and illustrate the importance of this model for study of sensory neuropathy.
Department of Biology, Boston College, Chestnut Hill, Massachusetts 02467, USA.
Tricia H
TH
Burdo
Krystyna
K
Orzechowski
Heather L
HL
Knight
Andrew D
AD
Miller
Kenneth
K
Williams
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D018450:Disease Progression; D005727:Ganglia, Spinal / Q000276:immunology / Q000473:pathology*; D015658:HIV Infections / Q000150:complications / Q000276:immunology / Q000473:pathology; D006801:Humans; D008253:Macaca mulatta; D008262:Macrophage Activation / Q000276:immunology; D010523:Peripheral Nervous System Diseases / Q000276:immunology / Q000473:pathology / Q000821:virology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000150:complications / Q000276:immunology / Q000473:pathology*; D015302:Simian Immunodeficiency Virus / Q000502:physiology; D014779:Virus Replication; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; C067980:CD68 antigen, human; D000097382:CD68 Molecule