HHV-6B infection promotes unique pro-inflammatory effects tied to neurocognitive decline and artherosclerosis
Virologist Ursula Gompels from the London School of Hygiene and Tropical Medicine has reported that HHV-6A and HHV-6B each express distinct chemokines that are uniquely capable of activating key inflammatory cytokines. Chemokine Receptor Type 2 (CCR2) is a receptor that controls monocyte chomoattractant proteins that cause monocyte infiltration, which is important in inflammatory diseases such as rheumatioid arthritis and in the response against tumors.
These inflammatory monocytic cells have also been identified as playing a role in a number of important inflammatory conditions such as multiple sclerosis, artherosclerosis, diabetic nephropathy, cognitive decline in the elderly and Alzehiemer’s Disease. HHV-6B chemokine U83B is specific for CCR2 and can chemoattract monocytes and some T-cells expressing CCR2+ cells for both latent and lytic infection. U83B enables CCR2 CD14 CD16+ monocytes to cross the blood brain barrier, and is responsible for attracting monocytes to the site of injury. HHV-6A’s cheomokine U83A is specific for promoting CCR1, CCR4, CCR5, CCR6 and CCR8 positive monocytes, dendritic, NK cells, and certain ‘skin-homing” T cells. The authors suggest that these virus-specific chemokines explain the difference in disease associations between HHV-6A and HHV-6B. HHV-6A has been associated with multiple sclerosis, gliomas and Hashimoto’s thyroiditis, while HHV-6B is a frequent cause of febrile seizures, and causes limbic encephalitis in transplant patients.
For more information, read the full paper.
Note from the HHV-6 Foundation staff:
One of the isoforms of CCR2 is CCLE, or the monocyte chemoattractant protein-1, and CCLE is expressed in high concentrations in the macrophages found in artherosclerotic plaques and in brain microglia. In addition, patients with Alzheimer’s have been found to have higher levels of inflammatory markers suggestive of infection, including C reactive protein, TNF alpha and CCLE (Gorelick 2012).
CCR2 has been associated with increased inflammation, brain infiltration and immunosenescence, and may play a role in a number of inflammatory conditions progression of inflammatory diseases. Some investigators have found an inverse relationship between the expression of CCR2 and cognitive function (Harries 2012).
At least one company, ChemoCentryx, is working on a drug candidate that targets CCR2, because of its role in diabetic nephropathy and Type 2 diabetes. They are currently conducting Phase II trials for their drug CCX140 which they describe as a potent and selective antagonist of CCR2.