Characterization of Human Immunodeficiency Virus (HIV)-Infected Cells in Infiltrates Associated With CNS Opportunistic Infections in Patients With HIV Clade C Infection

Abstract

Infection with human immunodeficiency virus (HIV) clade C is the most common HIV infection worldwide, yet its impact on the nervous system remains largely unknown. Autopsy studies from regions affected by this virus are scarce, and HIV dementia has only rarely been reported from these countries. Most patients who develop neurologic complications die of opportunistic infections. We thus conducted a neuropathologic study from a single institution in India to characterize the HIV-infected cells in the inflammatory infiltrates in a total of 15 cases (5 patients each who died of either CNS toxoplasmosis, tuberculosis, or cryptococcal meningitis). Nearly, all patients had HIV-infected cells in the brain, although these cells were most abundant in patients with toxoplasma encephalitis. Interestingly, none of the patients had any multinucleated giant cells. HIV-infected cells were found in the parenchyma, perivascular regions, and choroid plexus and found infiltrating the parenchyma from the meninges, suggesting multiple portals of entry into the brain. These findings suggest the possibility that patients, even if successfully treated for an opportunistic inflection, may be at high risk of developing HIV encephalitis and subsequent dementia.

Generation of Lineage-Related, Mucosally Transmissible Subtype C R5 Simian-Human Immunodeficiency Viruses Capable of AIDS Development, Induction of Neurological Disease, and Coreceptor Switching in Rhesus Macaques

“…The incidence and severity of neurological impairment have been reported to be lower among subtype C-infected patients than among subtype B-infected individuals (75)(76)(77)(78), with one study showing that MNGCs and multifocal microglial nodules, frequently found in clade B-infected patients, are absent in the brains of clade C-infected individuals (79). Initial analysis of a limited number of macaques with AIDS that had been infected i.r.…”

NMDA Receptor Activation by HIV-Tat Protein Is Clade Dependent

“…HIV was detected in infiltrating macrophages by immunostaining for p24 in each of these patients. The neuropathological findings of the first two patients have been previously reported (Mahadevan et al, 2007). A small piece of the tissue was placed in 700 l of Tris buffer (50 mM Tris pH 8.0, 100 mM EDTA, 100 mM NaCl, 1% SDS) and 20 l of proteinase K (20 mg/ml).…”

“…HIV clade C however, efficiently infects macrophages. Further, HIVinfected macrophages are found in the brains of clade C-infected patients (Mahadevan et al, 2007). One of the mechanisms by which HIV-infected macrophages cause neuronal injury involves the extracellular release of Tat protein, which may then act directly on neurons to cause toxicity (Mattson et al, 2005).…”

Changes in MRS neuronal markers and T cell phenotypes observed during early HIV infection

“…NAA and Glx of the white matter were not associated with the total CD8 ϩ T cell population. Neither CD8 ϩ naïve nor central memory cells were related to NAA [23][24][25] A handful of case studies during PHI have described profound neurologic changes that can occur with HIV seroconversion including transient encephalopathy, frank meningoencephalitis, and demyelinating disease. 20,21,25 However, it is generally believed this early infection in non-rapid disease animals and humans is typically transient and productive infection is not thought to occur again until the development of AIDS.…”