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Paving the path to HIV neurotherapy: Predicting SIV CNS disease
Sarah E Beck1, Suzanne E Queen1, Kenneth W Witwer1
1Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States.
Abstract:
HIV-induced damage to the CNS remains a major challenge for over 30 million people in the world despite the successes of combined antiretroviral therapy in limiting viral replication. Predicting development and progression of HIV-associated CNS disease is crucial because prevention and early intervention could be more effective than attempts to promote repair. The SIV/macaque model is the premier platform to study HIV neuropathogenesis, including discovery of predictive factors such as neuroprotective host genes and both blood and CSF biomarkers that precede and predict development of SIV CNS disease. This report details the role of macaque MHC class I genes, longitudinal alterations in biomarkers in the circulation, and expression of inflammatory and neuronal damage markers in CSF using samples from SIV-inoculated pigtailed macaques collected during acute, asymptomatic, and terminal stages of infection.
Insights
Predicting HIV-associated central nervous system (CNS) disease is crucial. This study used the SIV/macaque model to identify host genes and biomarkers that predict CNS disease progression in HIV infection.
Area of Science:
- Neuroscience
- Immunology
- Virology
Background:
- HIV-associated central nervous system (CNS) damage remains a significant global health challenge despite effective antiretroviral therapies.
- Predicting the onset and progression of HIV-associated CNS disease is vital for timely intervention and improved patient outcomes.
- The SIV/macaque model is a critical tool for investigating HIV neuropathogenesis and identifying predictive factors.
Purpose of the Study:
- To investigate the role of macaque MHC class I genes in HIV neuropathogenesis.
- To identify longitudinal changes in blood and cerebrospinal fluid (CSF) biomarkers that predict the development of SIV-induced CNS disease.
- To analyze inflammatory and neuronal damage markers in CSF across different stages of SIV infection.
Main Methods:
- Utilized the SIV/macaque model, a well-established platform for studying HIV neuropathogenesis.
- Collected longitudinal samples from SIV-inoculated pigtailed macaques at acute, asymptomatic, and terminal stages of infection.
- Analyzed macaque MHC class I gene expression, circulating biomarkers, and CSF markers of inflammation and neuronal damage.
Main Results:
- Identified specific macaque MHC class I genes associated with neuropathogenesis.
- Documented longitudinal alterations in blood biomarkers preceding SIV CNS disease.
- Observed changes in inflammatory and neuronal damage markers in CSF correlating with disease progression.
Conclusions:
- Macaque MHC class I genes play a role in HIV neuropathogenesis.
- Circulating and CSF biomarkers can predict the development and progression of SIV-associated CNS disease.
- Early identification of predictive biomarkers in the SIV/macaque model offers potential for improved management of HIV-associated neurological complications.
