HEPATITIS C VIRUS NEUROINVASION: IDENTIFICATION OF INFECTED CELLS

[Guest guest]

J Virol. 2008 Nov 19. [Epub ahead of print]

HEPATITIS C VIRUS NEUROINVASION: IDENTIFICATION OF INFECTED CELLS.

Wilkinson J, Radkowski M, Laskus T.

St. ph'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.

PMID: 19019968 [PubMed - as supplied by publisher

[Guest guest]

J Virol. 2008 Nov 19. [Epub ahead of print]

HEPATITIS C VIRUS NEUROINVASION: IDENTIFICATION OF INFECTED CELLS.

Wilkinson J, Radkowski M, Laskus T.

St. ph'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.

PMID: 19019968 [PubMed - as supplied by publisher