Hepatitis C Virus in Brain

HEPATITIS C VIRUS NEUROINVASION: IDENTIFICATION OF INFECTED CELLS.

Wilkinson J, Radkowski M, Laskus T.
St. Joseph's Hospital and Medical Center, Phoenix, Arizona; Institute of Infectious Diseases, Warsaw Medical University, Warsaw, Poland.

Hepatitis C virus (HCV) infection is often associated with cognitive dysfunction and depression. HCV sequences and replicative forms were detected in autopsy brain tissue and cerebrospinal fluid from infected patients suggesting direct neuroinvasion. However, the phenotype of cells harboring HCV in brain remains unclear. We studied autopsy brain tissue from 12 HCV-infected patients, 6 of these patients were coinfected with HIV. Cryostat sections of frontal cortex and subcortical white matter were stained with monoclonal antibodies specific for microglia/macrophages (CD68), oligodendrocytes (CNPase), astrocytes (GFAP) and neurons (NeuN), separated by laser capture microscopy (LCM) and tested for the presence of positive and negative strand HCV RNA. Sections were also stained with antibodies to viral nonstructural protein 3 (NS3), separated by LCM and phenotyped by real-time PCR. Finally, sections were also double stained with antibodies specific for cell phenotype and HCV NS3. HCV RNA was detected in CD68-positive cells in 8 patients and negative strand HCV RNA, which is a viral replicative form, was found in 3 of these patients. HCV RNA was also found in astrocytes from 3 patients, but negative strand RNA was not detected in these cells. In double immunostaining, 83%-95% of cells positive for HCV NS3 were also CD68-positive, while 4% to 29% were GFAP-positive. NS3-positive cells were negative for neuron and oligodendrocyte phenotypic markers. In conclusion, HCV infects brain microglia/macrophages and to a lesser extent astrocytes. Our findings could explain the biological basis of neurocognitive abnormalities in HCV infection.

http://www.ncbi.nlm.nih.gov/pubmed/19019968?ordinalpos=8&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum

[CockSparrow]

Is it just me or is this not surprising.
HCV is in our blood. Our brain requires a blood supply, although with some people you have to wonder whether they are getting enough.

Wherever blood goes HCV is sure to follow.
Or have i missed something

CS

[merryBe]

great so now I've got vindication!!

Squirrliness is us !!!!!!!

well, at least now I can stop worrying about all those white spots on my brain scan MRI...there just where "our little friends" have been chewing away.

say hello to "my little friends"!!!!

Bats in the bellfrie......hello.

mb

[CoWriter]

"Wherever blood goes HCV is sure to follow.
Or have i missed something"
----------------------

Years ago, when they started studying staining by using dyes to make organs more visible, they found that when they injected a dye, it would stain all the organs except the brain.  At first they thought maybe the brain just wasn't picking up as much of the dye.  

In a later experiment, they found that when they injected the dye into the spinal fluid, the brain would become dyed, but the rest of the body would not.  So this clearly demonstrated the existence of some sort of barrier between the two.

That's how they found the blood-brain barrier.

The barrier is made of endothelial cells that fit tightly together so substances cannot pass from the bloodstream. It protects the brain by restricting the passage of toxins, bacteria, etc (while allowing oxygen in).  However, viruses can bypass the blood-brain barrier by attaching themselves to circulating immune cells.

According to the prevailing Trojan Horses hypothesis, circulating lymphocytes cross the blood-brain barrier carrying HCV to the central nervous system ...and the virus is then replicated in the macrophages and the microglia (brain cells that act as the first and main form of active immune defense) in the brain as a separate compartment.
  
HCV RNA negative strand, which shows replication, has been found in the brain tissue from Hep C patients, proving that indeed, the Hepattis C virus has found a way to cross the blood- brain barrier.

Co

[epiphiny]

Will it ever end....

I always suspected the depression link but now I have a reason for my eccentricity and absent-mindedness...

Do you think this is reversible or will I just continue to become more and more demented?

[jankar]

lack of cognitve function - that scares me - particularly when aging........