Chapter 21 : Hepatitis C Virus: Variability, Extrahepatic Replication, and Neuroinvasion

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Hepatitis C Virus: Variability, Extrahepatic Replication, and Neuroinvasion, Page 1 of 2

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Recent studies focusing on Hepatitis C virus (HCV) survival strategies revealed that viral proteins may interfere with pathways of retinoid-acid-inducible gene I and Toll-like receptor 3, which constitute two major pathways of host defense triggered by viral nucleic acids. In particular, HCV seems to interfere at several different points with interferon (IFN) and IFN-stimulated gene signaling. A powerful strategy employed by the virus is genetic variability resulting in the constant and dynamic development of variants capable of avoiding eradication by host defenses. Several studies have reported that transmission of infection may be limited to a few variants present within the quasispecies population. Thus, viral populations found in children infected at birth were found to be more homogeneous than those in mothers. HCV infection is common among HIV-positive patients, as the two pathogens share similar routes of transmission. HCV is a positive-strand RNA virus, which replicates through negative-strand RNA, the presence of which could be regarded as direct evidence of ongoing replication. HCV RNA-negative strand was detected only in a minority of cases; however, it is likely that the strand-specific assays are not sensitive enough to detect low-level extra hepatic replication. Infected macrophages and microglia cells could release proinflammatory cytokines, such as tumor necrosis factor (TNF)- α, interleukin-1 (IL-1), and IL-6, neurotoxins such as nitric oxide, and viral proteins, which could induce alteration in brain function leading in turn to neurocognitive dysfunction and depression.

Citation: Radkowski M, Nasseri J, Laskus T. 2009. Hepatitis C Virus: Variability, Extrahepatic Replication, and Neuroinvasion, p 295-311. In Goodkin K, Shapshak P, Verma A (ed), The Spectrum of Neuro-AIDS Disorders. ASM Press, Washington, DC. doi: 10.1128/9781555815691.ch21

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A working hypothesis regarding the effects of HCV on brain. HCV can infect PBMC, particularly macrophages, and this process is facilitated by concomitant HIV coinfection. Infected macrophages could cross the blood-brain barrier. Following the entry into the brain, infected macrophages release proinflammatory cytokines, which could induce alteration in brain function leading in turn to neurocognitive dysfunction. HCV infection may be also associated with oxidative stress, which could be due to release of reactive oxygen species by macrophages or to the direct effect of viral proteins on mitochondria.

Citation: Radkowski M, Nasseri J, Laskus T. 2009. Hepatitis C Virus: Variability, Extrahepatic Replication, and Neuroinvasion, p 295-311. In Goodkin K, Shapshak P, Verma A (ed), The Spectrum of Neuro-AIDS Disorders. ASM Press, Washington, DC. doi: 10.1128/9781555815691.ch21
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