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Published on: September 19, 2010
[Astrocytes and lentivirus infection in an experimental models of macaque infected with SIVmac251]
G Guillemin1, J Croitoru, F D Boussin
1Service de Neurovirologie, Commissariat à l'énergie atomique, DSV/DRM, Fontenay-aux-Roses. g.guillemin@cfi.UNSW.EDU.au
Abstract:
The present study demonstrates the susceptibility of astrocytes to infection with SIVmac251. Indeed, primary cultures of astrocytes derived from simian adult brains, can be infected in vitro with the SIVmac251. Results show that SIVmac251 establishes a persistent infection in primary astroglial cultures and that viral replication can be reactivated by TNF-alpha, GM-CSF, IFN-gamma. Viral proteins as Nef, Rev, Vpx and occasionally gp120/160 are evidenced by immunocytochemistry. In vivo SIVmac251 and/or HIV-2 infected astrocytes have been isolated from brains of macaques following ex vivo primary cultures. The whole of these results demonstrated that, in this model, SIV establishes a persistent state of infection of astrocytes, that viral replication can be reactivated by cytokines and moreover suggest strongly an in vivo infection of astrocytes in the brain of these infected macaques.
Insights
Simian immunodeficiency virus (SIVmac251) can persistently infect astrocytes in vitro, with replication reactivated by cytokines. Astrocytes from SIV-infected macaques also showed evidence of infection, suggesting astrocytes play a role in SIV pathogenesis.
Area of Science:
- Neuroscience
- Virology
- Immunology
Context:
- Astrocytes are crucial glial cells in the central nervous system.
- Simian immunodeficiency virus (SIV) infection in macaques serves as a model for human immunodeficiency virus (HIV) pathogenesis.
- Understanding glial cell involvement in viral infections is critical for neuroAIDS research.
Purpose:
- To investigate the susceptibility of primary astrocyte cultures to SIVmac251 infection.
- To determine if SIV establishes a persistent infection in astrocytes.
- To identify factors that can reactivate viral replication in infected astrocytes.
Summary:
- Primary astrocyte cultures derived from simian brains were susceptible to in vitro infection with SIVmac251.
- SIVmac251 established a persistent infection in these astroglial cultures.
- Viral replication was reactivated by specific cytokines, including TNF-alpha, GM-CSF, and IFN-gamma.
- Viral proteins (Nef, Rev, Vpx, gp120/160) were detected via immunocytochemistry.
- Astrocytes isolated from the brains of SIV-infected macaques also showed evidence of infection, suggesting in vivo relevance.
Impact:
- Demonstrates astrocytes are a target for SIV infection.
- Highlights the potential for cytokine-mediated viral reactivation in the brain.
- Provides evidence for in vivo infection of astrocytes in SIV-infected macaques.
- Suggests astrocytes may contribute to SIV/HIV neuropathogenesis.
