Pathogenesis of Hepatitis C Virus Coinfection in the Brains of Patients Infected with HIV

Letendre, Scott; Paulino, Amy; Rockenstein, Edward; Adame, Anthony; Crews, Leslie; Cherner, Mariana; Heaton, Robert K.; Ellis, Ronald J.; Everall, Ian; Grant, Igor; Masliah, Eliezer

doi:10.1086/519285

Cited by 125 publications

(120 citation statements)

References 51 publications

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“…As already illustrated, Pfefferbaum/Sullivan [36,119] have demonstrated the significant contribution of alcohol abuse among commonly presenting HIV-infected populations. Much has also been written about other subpopulations within HIV-infected cohorts, such as drug abuse [120,121], hepatitis C coinfection [122,123], etc. The use of more controlled research designs will not only broaden our understanding of the neurological effects of these additional factors, but will improve both our understanding of the specific mechanisms of HIV-associated CNS injury and our potential for developing a specific neuropathogenic model.…”

Section: Therapeutic Benefits Of Imaging and Future Studiesmentioning

confidence: 99%

The Role of Medical Imaging in Defining CNS Abnormalities Associated with HIV-Infection and Opportunistic Infections

et al. 2011

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Summary:In this review of the current literature, we examine the role of medical imaging in providing new and relevant information on central nervous system (CNS) injury associated with human immunodeficiency virus (HIV) infection and various clinical manifestations of this injury. Common imaging modalities used to examine CNS injury in HIV infection include structural magnetic resonance imaging, magnetic resonance spectroscopy, diffusion tensor imaging, functional MRI, and positron emissions tomography. Clinical implications for the findings are discussed for each of these modalities individually and collectively. In addition, the direction for future studies is suggested in an attempt to provide possible methods that might answer the many questions that remain to be answered on the evolution and progression of CNS injury in the context of HIV infection.

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Section: Therapeutic Benefits Of Imaging and Future Studiesmentioning

confidence: 99%

The Role of Medical Imaging in Defining CNS Abnormalities Associated with HIV-Infection and Opportunistic Infections

et al. 2011

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“…The only published study of the subject was limited in its approach to the immunostaining of viral proteins and included only HIV-positive patients (23). In the current study, which employed a multipronged approach consisting of laser capture microscopy (LCM), strand-specific HCV RNA amplification, and immunostaining, we identified CD68 ϩ cells as the dominant brain cell population infected by HCV.…”

mentioning

confidence: 99%

Hepatitis C Virus Neuroinvasion: Identification of Infected Cells

Wilkinson

Radkowski

Laskus

2009

J Virol

179

140

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Hepatitis C virus (HCV) infection often is 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 whom were coinfected with human immunodeficiency virus. Cryostat sections of frontal cortex and subcortical white matter were stained with monoclonal antibodies specific for microglia/macrophages (CD68), oligodendrocytes (2,3-cyclic nucleotide 3-phosphodiesterase), astrocytes (glial fibrillary acidic protein [GFAP]), and neurons (neuronal-specific nuclear protein); separated by laser capture microscopy (LCM); and tested for the presence of positive-and negative-strand HCV RNA. Sections also were stained with antibodies to viral nonstructural protein 3 (NS3), separated by LCM, and phenotyped by real-time PCR. Finally, sections were double stained with antibodies specific for the cell phenotype and HCV NS3. HCV RNA was detected in CD68-positive cells in eight patients, and negative-strand HCV RNA, which is a viral replicative form, was found in three of these patients. HCV RNA also was found in astrocytes from three patients, but negative-strand RNA was not detected in these cells. In double immunostaining, 83 to 95% of cells positive for HCV NS3 also were 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.Patients with chronic hepatitis C virus (HCV) infection were reported to be more likely to manifest impairments in the quality of life, fatigue, and depression than patients with liver disease of other etiology (3,12,14,39). More recently, HCV infection was associated with cognitive dysfunction (11, 13). Importantly, Forton and colleagues, using proton magnetic resonance spectroscopy ( 1 H MRS), demonstrated elevations of choline/creatine ratios in basal ganglia and white matter in patients with mild hepatitis C disease that were not present in healthy volunteers or patients with hepatitis (9, 11). The presence of similar abnormalities consisting of increased choline and reduced N-acetyl aspartate levels among HCV-positive patients relative to those of controls has since been reported by other researchers (25, 41). The 1 H MRS changes in HCV infection are different from those seen in hepatic encephalopathy, where the choline ratios are depressed (40), but are similar to those found in patients with human immunodeficiency virus (HIV) infection (24, 26). Additional evidence for the biological basis of HCV-related cognitive dysfunction is provided by a recent report showing differences in gene expression patterns between brain tissue from HCV-positive and HCV-nega...

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“…This hypothesis is supported by a recent study reporting that efavirenz is associated with cognitive disorders in otherwise asymptomatic HIV-infected patients (20). Other previously reported risk factors for HAND include a decreased CD4 count, anemia, declining platelet count, high HIV-RNA viral load in the CNS, and hepatitis C coinfection (20)(21)(22).…”

Section: Discussionmentioning

confidence: 60%

High prevalence of HIV-associated neurocognitive disorder in HIV-infected patients with a baseline CD4 count ≤ 350 cells/μL in Shanghai, China

et al. 2013

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Pathogenesis of Hepatitis C Virus Coinfection in the Brains of Patients Infected with HIV

Cited by 125 publications

References 51 publications

The Role of Medical Imaging in Defining CNS Abnormalities Associated with HIV-Infection and Opportunistic Infections

The Role of Medical Imaging in Defining CNS Abnormalities Associated with HIV-Infection and Opportunistic Infections

Hepatitis C Virus Neuroinvasion: Identification of Infected Cells

High prevalence of HIV-associated neurocognitive disorder in HIV-infected patients with a baseline CD4 count ≤ 350 cells/μL in Shanghai, China

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