Innate immunity in the pathogenesis of retrovirus infection in CNS

[natasa778]

Abstract
Neuroinflammation, including astrogliosis, microgliosis, and the production of proinflammatory cytokines and chemokines is a common response in the central nervous system (CNS) to virus infection, including retrovirus infection. However, the contribution of this innate immune response in disease pathogenesis remains unresolved. Analysis of the neuroinflammatory response to polytropic retrovirus infection in the mouse has provided insight into the potential contribution of the innate immune response to retrovirus-induced neurologic disease. In this model, retroviral pathogenesis correlates with the induction of neuroinflammatory responses including the activation of astrocytes and microglia, as well as the production of proinflammatory cytokines and chemokines. Studies of the neurovirulent determinants of the polytropic envelope protein as well as studies with knockout mice suggest that retroviral pathogenesis in the brain is multifaceted and that cytokine and chemokine production may be only one mechanism of disease pathogenesis. Analysis of the activation of the innate immune response to retrovirus infection in the CNS indicates that toll-like receptor 7 (TLR7) is a contributing factor to retrovirus-induced neuroinflammation, but that other factors can compensate for the lack of TLR7 in inducing both neuroinflammation and neurologic disease.

http://www.springerlink.com/content/j363643687144423/

 

[Gerwyn]

Abstract
Neuroinflammation, including astrogliosis, microgliosis, and the production of proinflammatory cytokines and chemokines is a common response in the central nervous system (CNS) to virus infection, including retrovirus infection. However, the contribution of this innate immune response in disease pathogenesis remains unresolved. Analysis of the neuroinflammatory response to polytropic retrovirus infection in the mouse has provided insight into the potential contribution of the innate immune response to retrovirus-induced neurologic disease. In this model, retroviral pathogenesis correlates with the induction of neuroinflammatory responses including the activation of astrocytes and microglia, as well as the production of proinflammatory cytokines and chemokines. Studies of the neurovirulent determinants of the polytropic envelope protein as well as studies with knockout mice suggest that retroviral pathogenesis in the brain is multifaceted and that cytokine and chemokine production may be only one mechanism of disease pathogenesis. Analysis of the activation of the innate immune response to retrovirus infection in the CNS indicates that toll-like receptor 7 (TLR7) is a contributing factor to retrovirus-induced neuroinflammation, but that other factors can compensate for the lack of TLR7 in inducing both neuroinflammation and neurologic disease.

http://www.springerlink.com/content/j363643687144423/

any idea if creb fits in?

 

[natasa778]

Absolutely! I have loads on it, starting about 1/3 page down here (mostly relates to neuronal CREB-induced gene expression but more on glial cells towards the bottom of the page..). also some on this page on immunity/inflammation and calcium channelopathy , again 1/3 down...


also here:
...Dysregulation of calcium homeostasis underlies neurological disturbances in neuro-AIDS. The virus seems to enter the brain in the early stages of infection and arising pathological processes in the brain and CNS are only in part affected by HIV-dependent processes in the periphery. Although the virus does not seem to directly infect the neurons, two of its identified viral proteins are neuroxic - the viral coat protein gp120 and the transcription regulator Tat. Both of these proteins can induce apoptosis of cultured neurons and can render neurons vulnerable to excitotoxicity and oxidative stress. Both gp120 and Tat disrupt neuronal calcium homeostasis by perturbing calcium-regulating systems in the plasma membrane and endoplasmic reticulum. By altering voltage-dependent calcium channels, glutamate receptor channels, and membrane transporters, these proteins promote excessive calcium entry, production of free radicals and mitochondrial dysfunction [12394783] (see Oxidative_Stress and Mitochondrial issues in autism). These effects are at least partly mediated via their effect on chemokine receptors, which are widely expressed on neurons and some of which are able to activate the calcium and cAMP-dependent transcription factor CREB (see Brain) [9826729]. In addition, glial cells were also found to contribute to chemokine upregulation in the CNS and so to contribute to neurological damage [15163738, 11744246]. (see chapter below re chemokine receptors on neurons and glial cells)....


note most references related to neuronal CREB, but as its levels are high in microglia no reason it would not be involved in same/similar ways..

 

[Jenny]

Thanks natasa

This links nicely with the results that people with ME get from the Acumen test - high intracellular calcium. And also with the success that some people have with calcium channel blockers like nimodipine.

I took nimodipine for 6 weeks after a brain haemorrhage and felt nearly 100%.

Jenny