More about HERV's and microglia activation
Posted: Sat Jul 13, 2019 1:04 am
New review about the role of HERVs in microglia activation, following Kremer's paper from last May (available from the second post ot the thread viewtopic.php?f=59&t=30971). This researchers confirm again the previously reported associations: A specific HERV (pHEV-W), activated microglia and demyelination, like Kremer's model predicted.
https://www.pnas.org/content/early/2019 ... 1909786116
The pHEV-W envelope protein has been described in the CNS in patients with MS (23, 24) and is confirmed in this study, with the protein being found in the extracellular parenchyma and within activated microglia.
The microglia seem to be closely associated with demyelinating axons. This protein can inhibit development of oligodendrocytes (OL), the cells that elaborate and maintain myelin as an extension and modification of their plasma membrane, and antibody to that protein can neutralize the inhibitory effect (25, 26).
Pathology represents a “snapshot” in time, how would one prove or support a causative role for activated microglia that have apparently phagocytized the envelope protein. Kremer et al. (13) have performed a series of elegant in vitro studies demonstrating that, at least in vitro, the microglia respond to the envelope protein as a proinflammatory stimulus. The microglia, in turn, produce proinflammatory cytokines which can further cause damage to myelin and axons and fail to produce protective factors.
[...]
What other ways might pHEV-W protein be involved in MS pathogenesis? How does the possible involvement of pHEV-W square with evidence for other viruses in MS, particularly EBV?
There is a role for EBV and other viruses in MS, as they can serve to activate the gene for HEV-W, leading to increased expression of the envelope protein (7, 35). It is still not clear that pHEV-W is first activated within the CNS or whether activation in the CNS is initiated by infiltrating inflammatory cells which have been shown to express the envelope protein.
https://www.pnas.org/content/early/2019 ... 1909786116
The pHEV-W envelope protein has been described in the CNS in patients with MS (23, 24) and is confirmed in this study, with the protein being found in the extracellular parenchyma and within activated microglia.
The microglia seem to be closely associated with demyelinating axons. This protein can inhibit development of oligodendrocytes (OL), the cells that elaborate and maintain myelin as an extension and modification of their plasma membrane, and antibody to that protein can neutralize the inhibitory effect (25, 26).
Pathology represents a “snapshot” in time, how would one prove or support a causative role for activated microglia that have apparently phagocytized the envelope protein. Kremer et al. (13) have performed a series of elegant in vitro studies demonstrating that, at least in vitro, the microglia respond to the envelope protein as a proinflammatory stimulus. The microglia, in turn, produce proinflammatory cytokines which can further cause damage to myelin and axons and fail to produce protective factors.
[...]
What other ways might pHEV-W protein be involved in MS pathogenesis? How does the possible involvement of pHEV-W square with evidence for other viruses in MS, particularly EBV?
There is a role for EBV and other viruses in MS, as they can serve to activate the gene for HEV-W, leading to increased expression of the envelope protein (7, 35). It is still not clear that pHEV-W is first activated within the CNS or whether activation in the CNS is initiated by infiltrating inflammatory cells which have been shown to express the envelope protein.