Pathogenesis of simian immunodeficiency virus-induced alterations in macaque trigeminal ganglia.
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.
Laast
Victoria A
VA
Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Pardo
Carlos A
CA
Tarwater
Patrick M
PM
Queen
Suzanne E
SE
Reinhart
Todd A
TA
Ghosh
Mimi
M
Adams
Robert J
RJ
Zink
M Christine
MC
Mankowski
Joseph L
JL
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
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015683:Gene Products, gag; D054334:Viral Regulatory and Accessory Proteins; C067980:CD68 antigen, human; D000097382:CD68 Molecule