Central Nervous System Inflammation and Infection during Early, Nonaccelerated Simian-Human Immunodeficiency Virus Infection in Rhesus Macaques
Abstract
Studies utilizing highly pathogenic simian immunodeficiency virus (SIV) and simian-human immunodeficiency virus (SHIV) have largely focused on the immunopathology of the central nervous system (CNS) during end-stage neurological AIDS and SIV encephalitis. However, this may not model pathophysiology in earlier stages of infection. In this nonaccelerated SHIV model, plasma SHIV RNA levels and peripheral blood and colonic CD4 + T cell counts mirrored early human immunodeficiency virus (HIV) infection in humans. At 12 weeks postinfection, cerebrospinal fluid (CSF) detection of SHIV RNA and elevations in IP-10 and MCP-1 reflected a discrete neurovirologic process. Immunohistochemical staining revealed a diffuse, low-level CD3 + CD4 − cellular infiltrate in the brain parenchyma without a concomitant increase in CD68/CD163 + monocytes, macrophages, and activated microglial cells. Rare SHIV-infected cells in the brain parenchyma and meninges were identified by RNAScope in situ hybridization. In the meninges, there was also a trend toward increased CD4 + infiltration in SHIV-infected animals but no differences in CD68/CD163 + cells between SHIV-infected and uninfected control animals. These data suggest that in a model that closely recapitulates human disease, CNS inflammation and SHIV in CSF are predominantly mediated by T cell-mediated processes during early infection in both brain parenchyma and meninges. Because SHIV expresses an HIV rather than SIV envelope, this model could inform studies to understand potential HIV cure strategies targeting the HIV envelope.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jun 01, 2018
- Source ID
- 10.1128/jvi.00222-18
Entities
People
- Alexandra Schuetz
- Claire Deleage
- Decha Silsorn
- Denise C. Hsu
- Dutsadee Inthawong
- Eric Lombardini
- Jacob D. Estes
- Jintanat Ananworanich
- Khamis Tomusange
- Lishomwa C. Ndhlovu
- Matthew Wegner
- Merlin L Robb
- Nelson Michael
- Piyanate Sunyakumthorn
- Rawiwan Im-erbsin
- Robert J. O'connell
- Robin Burke
- Ruth M. Ruprecht
- Samir K. Lakhashe
- Sandhya Vasan
- Serena Spudich
- Victor G Valcour
- Weerawan Chuenarom
- Yanin Kuncharin
- Yuwadee Phuang-ngern
Organizations
- Armed Forces Research Institute of Medical Sciences
- Henry M. Jackson Foundation for the Advancement of Military Medicine
- National Institute of Allergy and Infectious Diseases
- Southwest National Primate Research Center
- Texas Biomedical Research Institute
- United States Army Medical Research and Development Command
- United States Military HIV Research Program
- University of Amsterdam
- University of California, San Francisco
- University of Hawaiʻi System
- Walter Reed Army Institute of Research
- Yale University