Journal Article

Neuropathology associated with feline immunodeficiency virus infection highlights prominent lymphocyte trafficking through both the blood-brain and blood-choroid plexus barriers

Grimes, Terence, Mabruk, Mohamad JEMF, Ryan, Gavin, Brankin, Brenda, Callanan, John J, Hosie, Margaret J., Jarrett, Oswald

2005

Overview

Feline immunodeficiency virus (FIV) infection in the cat is a well-evaluated model of human immunodeficiency virus (HIV)-1 infection in man with both viruses associated with significant neuropathology. Although studies in both HIV and FIV infections have shown that virus enters the brain in the acute stages of disease, little is known of the mechanisms of viral entry. The dissection of this stage is fundamental to the development of therapies that may prevent or modulate central nervous system (CNS) infection. The present study was designed to characterize the early sequential neuropathological changes following infection with FIVGL8, a strain known to enter the CNS in acute infection. Cats were infected either by the intraperitoneal (n = 13) or intravenous (n = 12) route with 2000 cat infectious units of virus. Histopathological assessments following intraperitoneal infections were at 4 (n = 2), 5 (n = 1), 8 (n = 3), 10 (n = 1), 16 (n = 1), 32 (n = 2), 52 (n = 2), and 104 (n = 1) weeks post infection whereas animals infected intravenously were examined (n = 3) at 1, 4, 10, and 23 weeks post infection. The most significant lesions following both routes of infection were lymphocyte-rich perivascular infiltrates within cerebral and cerebellar meninges, in choroid plexus and spinal cord dura mater and within epineurium of the sciatic nerve. In addition, following intravenous infection perivascular infiltrations were noted in parenchymal blood vessels primarily of cerebral white matter. Infiltrates were composed of CD79+ B cells and CD3+ T cells. The latter population contained a mixture of CD4+ and CD8+ cells. The severity of lesions increased in intensity in the 8- to 16-week period following infection and then began to wane. The evaluation of this large group of cats at multiple time points revealed pathology comparable with that of early stage HIV-1-associated encephalitis. Moreover, in contrast to previous FIV neuropathology studies, transient meningeal, choroid plexus, and parenchymal vascular pathology were consistent significant findings suggesting that, as in HIV-1 infection, blood-brain barrier and choroid plexus brain barrier integrity are both compromised in early infection.

• Publisher: Informa UK Ltd,Taylor & Francis,Nature Publishing Group
• Subject: Animals / Biological and medical sciences / Blood vessels / Blood-brain barrier / Blood-Brain Barrier - immunology / Blood-Brain Barrier - virology / Brain - immunology / Brain - pathology / Brain - virology / Cats / CD3 antigen / CD4 antigen / CD8 antigen / Central nervous system / Cerebellum / Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges / Choroid plexus / Choroid Plexus - immunology / Choroid Plexus - virology / Dura mater / Encephalitis / Encephalitis, Viral - immunology / Encephalitis, Viral - pathology / Encephalitis, Viral - virology / Feline Acquired Immunodeficiency Syndrome - immunology / Feline Acquired Immunodeficiency Syndrome - pathology / Feline immunodeficiency virus / Fundamental and applied biological sciences. Psychology / HIV / Human immunodeficiency virus / Human immunodeficiency virus 1 / Human viral diseases / Immune system / Immunodeficiency Virus, Feline / Infections / Infectious diseases / Intravenous administration / Lymphocytes - immunology / Lymphocytes - virology / Lymphocytes B / Lymphocytes T / Medical sciences / Meninges / Neuropathology / Pathology / Sciatic nerve / Spinal cord / Substantia alba / Vertebrates: nervous system and sense organs / Viral diseases / Viral diseases of the lymphoid tissue and the blood. Aids / Viral diseases of the nervous system / Viral Load / Viruses