Proinflammatory responses and microglial infection by murine retrovirus

natasa778

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http://tinyurl.com/ydfoqn7

Abstract
Proinflammatory cytokines and chemokines are often detected in brain tissue of patients with neurological diseases such as multiple sclerosis (MS), HIV-associated dementia (HAD) and Alzheimer's disease (AD). We have utilized a mouse model of retrovirus-induced neurological disease to examine how these proinflammatory responses contribute to neuropathogenesis. In previous studies with this model, a correlation was found between neurovirulence and cytokine and chemokine expression. However, it was unclear whether the induction of these cytokines and chemokines was in response to specific virus envelope determinants or was regulated by the level of virus infection in the brain. In the current study, we demonstrated that multiple polytropic retroviruses induced cytokine and chemokine mRNA expression following increased virus levels in the brain. Increased virus levels of polytropic viruses also correlated with increased neuropathogenesis. In contrast, the ecotropic retrovirus, FB29, did not induce cytokine or chemokine mRNA expression or neurological disease, despite virus levels either similar to or higher than the polytropic retroviruses. As polytropic and ecotropic viruses utilize different receptors for entry, these receptors may play a critical role in the induction of these innate immune responses in the brain
 

Hope123

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Yeah, the link does't work. Also, it's hard to tell from the abstract whether they use just a mouse model or a mouse virus. Still trying the get the terms down but my understanding is XMRV is a xenotropic virus which is different from polytropic and ecotropic mouse viruses.
 

natasa778

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I found this one also interesting, it again focuses on envelope protein being crucial in pathogenesis (another thread on this protein just discovered to be involved in immunoinvasion)

Increased neurovirulence of polytropic mouse retroviruses delivered by inoculation of brain with infected neural stem cells.

Following intraperitoneal (IP) inoculation of neonatal mice, the polytropic recombinant murine leukemia virus (MuLV), Fr98, induces a severe brain disease characterized by ataxia, seizures and death. In contrast, no apparent clinical neurological disease is seen after IP infection with Fr54, a polytropic MuLV differing from Fr98 in its envelope gene sequences. In the brain both Fr98 and Fr54 infect primarily capillary endothelial cells and microglia. However, the level of microglial infection by Fr98 is twofold higher than by Fr54, which might account for the difference in neurovirulence. In the present study, in order to test directly whether an increase in the number of microglia infected by Fr54 would be sufficient to induce clinical disease, we attempted to increase the level of Fr54 in the brain by changing the route of infection. After intraventricular inoculation with Fr54-infected neural stem cells (clone C17.2), a well-established vehicle for delivery of viruses and genes to the brain, mice became ataxic and died 4 weeks postinfection. In these mice induction of brain disease was correlated with a higher level of viral antigen in the cerebrum and an increase in the number of infected microglial cells in all brain regions examined compared with mice inoculated IP. In contrast, mice inoculated with neural stem cells infected with an ecotropic nonneurovirulent murine leukemia virus, FB29, developed no clinical disease in spite of evidence for widespread infection of microglia in brain. Since the main differences between Fr54 and FB29 are in the SU (gp70) region of the envelope gene, this region is most likely to account for the differences in induction of CNS disease seen in the current experiments. Copyright 1999 Academic Press.PMID: 10544079 Virology. 1999 Oct 10;263(1):23-9.Poulsen DJ, Favara C, Snyder EY, Portis J, Chesebro B. Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, Hamilton, Montana 59840, USA.
 
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Help for layman.

Please, the only thing I get from this is that they were trying to figure out the chicken or egg question when it comes to viruses and cytokines.

I don't even understand what conclusion they came to.

Please explain it someone.

Tina
 
G

Gerwyn

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Help for layman.

Please, the only thing I get from this is that they were trying to figure out the chicken or egg question when it comes to viruses and cytokines.

I don't even understand what conclusion they came to.

Please explain it someone.

These viruses have coats with lots of buttons the shape of these buttons depends on whether or not a virus causes disease

.These buttons are knobbly bits of protein of a particular shape.

Viruses with the same coats but different buttons are called serotypes.

Different serotypes differ in the gene sequences which cause the different buttons.

The two serotypes here only differed in a small number of nucleic acid(bits of gene) so this bit of gene was responsible for making a serotype infective and not the other fr54 has different buttons to fb29 so fr54 dangerous fb29 not