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(American Journal of Pathology. 2004;164:1157-1172.)
© 2004 American Society for Investigative Pathology

Correlation of Acute Humoral Response with Brain Virus Burden and Survival Time in Pig-Tailed Macaques Infected with the Neurovirulent Simian Immunodeficiency Virus SIVsmmFGb

Shawn P. O’Neil*{dagger}{ddagger}, Carolyn Suwyn*{dagger}, Daniel C. Anderson{dagger}, Genevieve Niedziela*, Juliette Bradley*, Francis J. Novembre*{ddagger}, James G. Herndon§ and Harold M. McClure{dagger}

From the Divisions of Microbiology and Immunology, * Research Resources, {dagger} and Neuroscience, § Yerkes National Primate Research Center; and the Departments of Microbiology and Immunology, {ddagger} and Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia

Infection of pig-tailed macaques with the simian immunodeficiency virus (SIV) isolate SIVsmmFGb frequently results in SIV encephalitis (SIVE) in addition to immunodeficiency and acquired immune deficiency syndrome. We used in situ hybridization to quantitate the number of SIV-infected cells in brain parenchyma, choroid plexus, and meninges from 17 macaques that developed acquired immune deficiency syndrome after infection with SIVsmmFGb. SIV-infected cells and histopathological lesions of SIVE were identified in 15 of 17 animals (88.2%), including 12 of 12 rapid progressors (RP) and 3 of 5 slow progressors (SP). The parenchymal virus burden was much greater in RP macaques than in the three SP macaques with SIVE (median values of 24.3 versus 0.3 infected cells/mm2, respectively; P < 0.05). Viral load differences between RP and SP with SIVE were less marked in choroid plexus (29.6 versus 12.8 infected cells/mm2, respectively) and meninges (133.0 versus 34.2 infected cells/mm2, respectively). A significant negative correlation was observed between the magnitude of the anti-SIV antibody titer at 1 month after inoculation and brain virus burden at necropsy (r = -0.614; P < 0.01). The close association between immune response and SIVE in this model should prove useful for identifying correlates of immune protection against primate lentiviral encephalitis.




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