Monocyte activation and differentiation augment human endogenous retrovirus expression: implications for inflammatory...

Area of Science:

• Neuroimmunology
• Virology
• Molecular Biology

Background:

• Human endogenous retroviruses (HERVs) are linked to inflammatory and macrophage-activating diseases like multiple sclerosis.
• Monocyte activation and differentiation impact retroviral transcription and replication.

Purpose of the Study:

• To investigate the role of monocyte activation and differentiation in the expression of HERV families (HERV-W, HERV-K, HERV-E, HERV-H).
• To examine HERV expression in human monocytes and brain tissue from patients with inflammatory brain diseases.

Main Methods:

• Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to analyze HERV RNA levels.
• Primary macrophages and U937 monocytoid cells were stimulated with phorbol-12-myristate-13-acetate (PMA) or lipopolysaccharide (LPS).
• HERV expression was also analyzed in autopsied brain tissue from patients with multiple sclerosis, HIV/AIDS, and Alzheimer's dementia.

Main Results:

• PMA or LPS stimulation led to significant increases (3- to 9-fold) in HERV-W, HERV-K, and HERV-H RNA levels in monocytes.
• Elevated reverse transcriptase activity and HERV RNA were detected in supernatants of stimulated U937 cells, reducible by a monocyte differentiation inhibitor.
• HERV-W and HERV-K expression was elevated in brain tissue from multiple sclerosis and HIV/AIDS patients, correlating with tumor necrosis factor-alpha (TNF-α) levels.

Conclusions:

• Increased HERV expression, particularly HERV-W and HERV-K, is associated with inflammatory brain diseases and elevated immune activity (e.g., TNF-α).
• The findings suggest that heightened HERV expression is a consequence of increased immune activity rather than a direct cause of distinct diseases.
• HERV-E expression was unaffected or decreased upon monocyte stimulation.