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Published on: September 19, 2010
OTK18 expression in brain mononuclear phagocytes parallels the severity of HIV-1 encephalitis
Kimberly A Carlson1, Jenae Limoges, Garrett D Pohlman
1Center for Neurovirology and Neurodegenerative Disorders, Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198-5215, USA.
Abstract:
OTK18 was isolated by mRNA differential display of human monocyte-derived macrophages (MDM) infected with human immunodeficiency virus type one (HIV-1). Northern blot and real-time reverse transcription polymerase chain reaction showed low levels of OTK18 expression in human tissue, which markedly increased during advanced HIV-1 encephalitis (HIVE). Immunocytochemistry, using rabbit polyclonal antisera, showed OTK18 localized to brain mononuclear phagocytes (MP) in moderate to severe HIV-1 encephalitis. OTK18 expression was selective and not found in HIV-1-infected brain tissue with limited neuropathological abnormalities, nor in cytomegalovirus encephalitis, multiple sclerosis, Alzheimer's disease, or uninfected control brains. Thus, OTK18 expression in brain mononuclear phagocytes is a signature for advanced HIV-1 encephalitis.
Insights
OTK18 gene expression increases in brain cells during advanced HIV-1 encephalitis. This finding identifies OTK18 as a potential biomarker for this severe neurological complication of HIV-1 infection.
Area of Science:
- Neuroscience
- Immunology
- Molecular Biology
Background:
- Human immunodeficiency virus type 1 (HIV-1) infection can lead to severe neurological complications, including HIV-1 encephalitis (HIVE).
- Identifying specific molecular markers associated with the progression of HIVE is crucial for diagnosis and understanding disease mechanisms.
Purpose of the Study:
- To identify novel genes expressed in macrophages during HIV-1 infection.
- To investigate the role and expression patterns of OTK18 in the context of HIV-1 encephalitis.
Main Methods:
- mRNA differential display was used to isolate OTK18 from HIV-1 infected human monocyte-derived macrophages (MDM).
- Northern blot and real-time reverse transcription polymerase chain reaction (RT-PCR) were employed to assess OTK18 expression levels in human tissues.
- Immunocytochemistry was utilized to determine the cellular localization of OTK18 in brain tissue.
Main Results:
- OTK18 expression was found to be low in normal human tissues but significantly upregulated in advanced HIVE.
- OTK18 was specifically localized to brain mononuclear phagocytes (MP) in cases of moderate to severe HIVE.
- OTK18 expression was not detected in other neurological conditions like cytomegalovirus encephalitis, multiple sclerosis, Alzheimer's disease, or control brains.
Conclusions:
- OTK18 expression in brain mononuclear phagocytes serves as a specific indicator for advanced HIV-1 encephalitis.
- OTK18 represents a potential diagnostic biomarker for advanced HIVE.
