Monocyte activation and differentiation augment human endogenous retrovirus expression: Implications for inflammatory brain diseases
Version of Record online: 10 AUG 2001
Copyright © 2001 Wiley-Liss, Inc.
Annals of Neurology
Volume 50, Issue 4, pages 434–442, October 2001
How to Cite
Johnston, J. B., Silva, C., Holden, J., Warren, K. G., Clark, A. W. and Power, C. (2001), Monocyte activation and differentiation augment human endogenous retrovirus expression: Implications for inflammatory brain diseases. Ann Neurol., 50: 434–442. doi: 10.1002/ana.1131
- Issue online: 8 OCT 2001
- Version of Record online: 10 AUG 2001
- Manuscript Accepted: 24 MAY 2001
- Manuscript Revised: 21 MAY 2001
- Manuscript Received: 28 FEB 2001
- Canadian Institutes of Health Research
- Multiple Sclerosis Society of Canada
Human endogenous retroviruses (HERVs) have been implicated as causative agents in diseases characterized by inflammation and macrophage activation, such as multiple sclerosis. Because monocyte activation and differentiation influence retroviral transcription and replication, we investigated the contribution of these processes to the expression of four HERV families (HERV-W, HERV-K, HERV-E, and HERV-H) in human monocytes and autopsied brain tissue from patients with brain diseases associated with increased macrophage activity. Reverse transcriptase-polymerase chain reaction analysis of primary macrophages and U937 monocytoid cells stimulated with phorbol-12-myristate-13-acetate or lipopolysaccharide revealed three- to ninefold increases in HERV-W, HERV-K, and HERV-H RNA levels. In addition, elevated reverse transcriptase activity and HERV RNA were detectable in supernatants from PMA-stimulated U937 cultures, properties that could be attenuated with the inhibitor of monocyte differentiation threonine-lysine-proline. In contrast, stimulation of monocytes decreased or had no effect on HERV-E expression. Compared with controls, HERV-W and HERV-K expression was increased in brain tissue from patients with multiple sclerosis or human immunodeficiency virus infection or AIDS, with concomitant elevated tumor necrosis factor-α levels. Similarly, elevated HERV-W levels were detected in patients with Alzheimer's dementia only when tumor necrosis factor-α expression was also evident (2 of 6 cases). The detection of several HERVs in inflammatory brain diseases and the capacity to augment HERV expression in monocytes with compounds that influence cellular activity suggest that increased expression of these viruses is a consequence of increased immune activity rather than causative of distinct diseases.