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

Abstract

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 FIV(GL8), 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.

Canine Distemper Virus Uses both the Anterograde and the Hematogenous Pathway for Neuroinvasion

“…Once inside the CSF, the viruses may invade the different membranes surrounding the CNS, the ependyma, and the superficial lining of the cerebral cortex (34,49), followed by infection of neurons and glia cells in close proximity and subsequent spread into deeper layers (19,26,29). Taken together, these observations suggest that paramyxoviruses use classical hematogenous CNS invasion pathways described for several other neurotropic viruses (17,33).…”

Copolymer-1 Induces Adaptive Immune Anti-inflammatory Glial and Neuroprotective Responses in a Murine Model of HIV-1 Encephalitis

“…For feline immunodeficiency virus infection of cats, brain disease is characterized by infiltrates of CD79 ϩ and CD3 ϩ B and T cells (mixture of CD4 ϩ and CD8 ϩ cells). The severity of lesions for feline immunodeficiency virus infection increases in intensity in weeks and is comparable to what is seen in the early stages of HIVE (65). In human HIV disease, antiretroviral therapy can affect immune restoration, and neuropathological examinations have shown severe inflammatory and/or demyelinating lesions linked to intraparenchymal and perivascular infiltration by T lymphocytes (66).…”

Genetic diversity of Brazilian isolates of feline immunodeficiency virus

“…FIV-infected cats can exhibit illnesses including gingivitis, stomatitis, lymphoma, neurological disorders and wasting [13,28,33]. The hallmark of FIV infection is a progressive reduction in the number of circulating CD4 + lymphocytes which ultimately results in an impairment of immunity, similar to AIDS caused by human immunodeficiency virus (HIV) [38] .…”