HIV mediates a productive infection of the brain : AIDS (original) (raw)

Concise Communication

Wiley, Clayton A.a; Achim, Cristian L.a; Christopherson, Cindyc; Kidane, Yordac; Kwok, Shirleyc; Masliah, Eliezerd; Mellors, Johnb; Radhakrishnan, Lakshmia; Wang, Guojia; Soontornniyomkij, Virawudha

From the aDepartment of Pathology and the bDepartment of Medicine University of Pittsburgh Medical Center, Pittsburgh, PA, the cRoche Molecular Systems, Alameda, CA, and the dDepartment of Pathology and Neurosciences University of California San Diego La Jolla, CA, USA.

Sponsorship: This work was supported in part by NIMH Center grant 5P50MH45294 and by NIH grants NS-25178, MH46790, and NS33429.

Correspondence to: Dr Clayton A. Wiley, Presbyterian University Hospital, Neuropathology Division, A-506 200 Lothrop Street, Pittsburgh, PA, USA.

Received: 10 February 1999; revised: 30 March 1999; accepted: 11 May 1999.

Abstract

Background:

Approximately one quarter of patients with AIDS develop severe cognitive deficits called HIV-associated dementia complex. There is some controversy regarding the importance of viral load and distribution in mediating this neurologic disease.

Objective:

Brain HIV proviral and RNA loads were compared to define the molecular nature of HIV infection of the brain.

Method:

Neuropathologic examination was performed on brains from 10 autopsies of patients with AIDS that had short post-mortem intervals and no evidence of opportunistic infection. Viral DNA and RNA were extracted and quantified from multiple brain regions. These findings were compared with triple-label immunofluorescence for viral and cell markers.

Results:

Brains with histopathologic evidence of HIV encephalitis contained abundant HIV RNA and DNA. Regions without productive HIV infection showed minimal proviral load. By immunocytochemistry, only brain macrophages/microglia double labeled for viral proteins.

Conclusions:

HIV mediates a productive infection of brain macrophages/microglia. There was no evidence supporting the hypothesis of substantial neuronal or macroglial infection, or evidence of substantial proviral burden prior to the development of productive infection.