Novel method to quantify phenotypic markers of HIV-associated neurocognitive disorder in a murine SCID model

• Type of Material: Article
• Authors: Christina Gavegnano, Emory University; Woldeab Haile, Emory University; Raj Koneru, Emory University; Selwyn Hurwitz, Emory University; James Kohler, Emory University; William Tyor, Emory University; Raymond Schinazi, Emory University
• Language: English
• Date: 2020-09-08
• Publisher: SPRINGER
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2020, Journal of NeuroVirology, Inc.
• Final Published Version (URL): http://dx.doi.org/10.1007/s13365-020-00842-3
• Title of Journal or Parent Work: JOURNAL OF NEUROVIROLOGY
• Volume: 26
• Issue: 6
• Start Page: 838
• End Page: 845
• Grant/Funding Information: This work was funded in part by NIH grant 1RO1MH116695 (to RFS and WT), and P30AI050409 (Emory University Center for AIDS Research NIH grant P30AI050409) and VA Merit award 1I01BX001506-01A2 (to WT).
• Keywords: MONOCYTES; Neurosciences; Neurosciences & Neurology; COGNITIVE DYSFUNCTION; MOUSE MODEL; Virology; IMPAIRMENT; MICROGLIA; HUMAN-IMMUNODEFICIENCY-VIRUS; EXPRESSION; Brain; ENCEPHALITIS; HIV; Science & Technology; Life Sciences & Biomedicine; BRAIN; Inflammation; ASTROGLIOSIS; HAND; Macrophages

Abstract

Despite combined antiretroviral therapy (cART), HIV infection in the CNS persists with reported increases in activation of macrophages (MΦ), microglia, and surrounding astrocytes/neurons, conferring HIV-induced inflammation. Chronic inflammation results in HIV-associated neurocognitive disorders (HAND) with reported occurrence of up to half of individuals with HIV infection. The existing HAND mouse model used by laboratories including ours, and the effect of novel agents on its pathology present with labor-intensive and time-consuming limitations since brain sections and immunohistochemistry assays have to be performed and analyzed. A novel flow cytometry-based system to objectively quantify phenotypic effects of HIV using a SCID mouse HAND model was developed which demonstrated that the HIV-infected mice had significant increases in astrogliosis, loss of neuronal dendritic marker, activation of murine microglia, and human macrophage explants compared to uninfected control mice. HIV p24 could also be quantified in the brains of the infected mice. Correlation of these impairments with HIV-induced brain inflammation and previous behavioral abnormalities studies in mice suggests that this model can be used as a fast and relevant throughput methodology to quantify preclinical testing of novel treatments for HAND.