title: Pathogenesis of simian immunodeficiency virus-induced alterations in macaque trigeminal ganglia.
abstract: Peripheral neuropathy is the most frequent neurologic complication associated with human immunodeficiency virus (HIV) infection, yet its pathogenesis remains poorly understood. To study the mechanisms causing HIV-induced peripheral nervous system disease, we examined trigeminal ganglia obtained from simian immunodeficiency virus (SIV)-inoculated macaques. SIV-infected macaques developed multifocal trigeminal ganglionitis of varying severity characterized by multifocal mononuclear infiltrates, neuronophagia, and neuronal loss resembling reports of HIV-associated changes present in dorsal root ganglia. Neuronal density, measured by calculating the fractional area of trigeminal ganglia occupied by neurons, was significantly lower in SIV-infected macaques versus uninfected macaques (p = 0.001). To characterize the inflammatory cell population and measure productive viral infection in ganglia, trigeminal ganglia from SIV-infected macaques were immunostained for macrophage or cytotoxic lymphocyte markers and for SIV gp41. The extent of macrophage infiltration in trigeminal ganglia was inversely correlated with neuronal loss (p = 0.001), whereas cytotoxic lymphocyte infiltration was not associated with neuronal loss. These studies demonstrate that alterations in the somatosensory ganglia of SIV-infected macaques closely parallel those observed in HIV-infected individuals and show that study of SIV-infected macaques may help elucidate the pathophysiology of HIV-induced peripheral neuropathy.
authors.affiliation: Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Victoria A
authors.initials: VA
authors.lastname: Laast
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Pardo
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Tarwater
authors.forename: Suzanne E
authors.initials: SE
authors.lastname: Queen
authors.forename: Todd A
authors.initials: TA
authors.lastname: Reinhart
authors.forename: Mimi
authors.initials: M
authors.lastname: Ghosh
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Adams
authors.forename: M Christine
authors.initials: MC
authors.lastname: Zink
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Mankowski
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D018791:CD4 Lymphocyte Count / Q000379:methods; D002452:Cell Count / Q000379:methods; D002490:Central Nervous System / Q000473:pathology; D015967:Gene Expression Regulation, Viral / Q000502:physiology; D015683:Gene Products, gag / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D007239:Infections; D008251:Macaca; D018613:Microscopy, Confocal / Q000379:methods; D017933:Peripheral Nervous System / Q000473:pathology / Q000821:virology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000473:pathology* / Q000821:virology; D015302:Simian Immunodeficiency Virus; D013997:Time Factors; D012668:Trigeminal Ganglion / Q000473:pathology* / Q000821:virology*; D019562:Viral Load; D054334:Viral Regulatory and Accessory Proteins / Q000235:genetics / Q000378:metabolism; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015683:Gene Products, gag; D054334:Viral Regulatory and Accessory Proteins; C067980:CD68 antigen, human; D000097382:CD68 Molecule