Early viral brain invasion in iatrogenic human immunodeficiency virus infection

Abstract

We report a 68-year-old man who received an IV inoculation of WBCs for an indium radionuclide scan containing 600 to 700 tissue culture infectious doses of human immunodeficiency virus type 1 (HIV-1) from an HIV-1-infected individual. The recipient immediately received zidovudine, then was switched to dideoxyinosine and interferon-alpha, but died of hepatorenal syndrome and hepatic encephalopathy 15 days later. HIV-1 cultures were positive from the recipient's blood on day 14 but not days 0, 1, and 8. At autopsy, cultures of parietal lobe isolated HIV-1. HIV-1 nucleic acid was present in several brain areas, but not in several other organs, by two independent laboratories using the polymerase chain reaction. The brain showed mild perivascular cuffing and a mild lymphocytic meningitis, but there was no evidence of glial nodules, giant cells, or white matter abnormalities. HIV-1 pg41 viral antigen was seen by immunoperoxidase staining in rare infiltrating cells within perivascular and subpial spaces. Thus, HIV-1 was isolated from brain 15 days after mistaken HIV-1 inoculation and 1 day after virus was first recovered from blood.

SIV Encephalitis Lesions Are Composed of CD163+ Macrophages Present in the Central Nervous System during Early SIV Infection and SIV-Positive Macrophages Recruited Terminally with AIDS

“…9,20,38 Productive infection of the CNS can be detected within days to weeks of initial infection, primarily within perivascular macrophages, but then resolves until the development of AIDS (pre-ART) or chronic infection with HIVE lesion formation (post-ART). 23,32,38e42 Productive infection of the CNS at endstage disease may represent recrudescence of virus seeded in the CNS with primary/acute infection, reintroduction of virus into the CNS terminally with AIDS, or both.…”

Macrophage are the principal reservoir and sustain high virus loads in rhesus macaques after the depletion of CD4+ T cells by a highly pathogenic simian immunodeficiency virus/HIV type 1 chimera (SHIV): Implications for HIV-1 infections of humans

“…Macrophage and microglia in the central nervous system of patients with AIDS dementia complex were identified as one of the first nonlymphocyte cell lineages that supported virus replication (34,35). It is now appreciated that macrophage throughout the body become exposed to virus very early in the infection (36)(37)(38). This is also the case for SIV-infected rhesus monkeys, in which 10-12% of virus-infected lymph node cells were shown to be of macrophage lineage 7-12 days after infection (39).…”

In vivo 1H MRS of brain injury and repair during acute SIV infection in the macaque model of neuroAIDS

“…This is supported by several similarities between the human and the macaque shortly after retroviral infection. These include abnormalities of CSF, parenchymal findings of neuroinvasion, and behavioral changes (38,39). The long-term clinical implications of acute metabolic dynamics in the CNS occasioned by HIV are unknown, but may be important in the development of neurocognitive deficits.…”