title: Neuropathology of wild-type and nef-attenuated T cell tropic simian immunodeficiency virus (SIVmac32H) and macrophage tropic neurovirulent SIVmac17E-Fr in cynomolgus macaques.
abstract: The neuropathology of simian immunodeficiency (SIV) infection in cynomolgus macaques (Macaca fascicularis) was investigated following infection with either T cell tropic SIVmacJ5, SIVmacC8 or macrophage tropic SIVmac17E-Fr. Formalin fixed, paraffin embedded brain tissue sections were analysed using a combination of in situ techniques. Macaques infected with either wild-type SIVmacJ5 or neurovirulent SIVmac17E-Fr showed evidence of neuronal dephosphorylation, loss of oligodendrocyte and CCR5 staining, lack of microglial MHC II expression, infiltration by CD4⁺ and CD8⁺ T cells and mild astrocytosis. SIVmacJ5-infected animals exhibited activation of microglia whilst those infected with SIVmac17E-Fr demonstrated a loss of microglia staining. These results are suggestive of impaired central nervous system (CNS) physiology. Furthermore, infiltration by T cells into the brain parenchyma indicated disruption of the blood brain barrier (BBB). Animals infected with the Δnef-attenuated SIVmacC8 showed microglial activation and astrogliosis indicative of an inflammatory response, lack of MHC II and CCR5 staining and infiltration by CD8⁺ T cells. These results demonstrate that the SIV infection of cynomolgus macaque can be used as a model to replicate the range of CNS pathologies observed following HIV infection of humans and to investigate the pathogenesis of HIV associated neuropathology.
authors.affiliation: Division of Retrovirology, National Institute of Biological Standards and Control, Blanche Lane, South Mimms, Hertfordshire, EN6 3QG, UK.
authors.forename: Sean
authors.initials: S
authors.lastname: Clarke
authors.forename: Neil
authors.initials: N
authors.lastname: Berry
authors.forename: Claire
authors.initials: C
authors.lastname: Ham
authors.forename: Jack
authors.initials: J
authors.lastname: Alden
authors.forename: Neil
authors.initials: N
authors.lastname: Almond
authors.forename: Debbie
authors.initials: D
authors.lastname: Ferguson
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000473:pathology; D001921:Brain / Q000473:pathology* / Q000821:virology; D002465:Cell Movement; D004195:Disease Models, Animal; D005260:Female; D008252:Macaca fascicularis; D008264:Macrophages / Q000473:pathology / Q000821:virology*; D008297:Male; D017628:Microglia / Q000473:pathology; D009474:Neurons / Q000473:pathology; D019713:Receptors, CCR5 / Q000096:biosynthesis; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000473:pathology* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000472:pathogenicity / Q000502:physiology*; D013601:T-Lymphocytes / Q000473:pathology / Q000821:virology*; D056189:Viral Tropism; D014774:Virulence
chemical_list: D019713:Receptors, CCR5