Hepatitis C Virus in Lymphoid Cells of Patients Coinfected with Human Immunodeficiency Virus Type 1: Evidence of Active Replication in Monocytes/Macrophages and Lymphocytes

Laskus, Tomasz; Radkowski, Marek; Piasek, Andrzej; Nowicki, Marek; Horban, Andrzéj; Cianciara, J; Rakela, Jorge

doi:10.1086/315283

Cited by 207 publications

(181 citation statements)

References 45 publications

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“…9 Because brain microglial cells are tissue-resident macrophages of blood monocytic origin, 13 we postulate that they also could support HCV replication. Our findings support this hypothesis because HCV replicative forms were detected in the CNS of both studied subjects, although the lineage of infected cells was not established.…”

Section: Discussionmentioning

confidence: 99%

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Detection of hepatitis C virus sequences in brain tissue obtained in recurrent hepatitis C after liver transplantation

et al. 2002

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Patients with chronic hepatitis C frequently report tiredness, easy fatigability, and depression. The aim of this study is to determine whether hepatitis C virus (HCV) replication could be found in brain tissue in patients with hepatitis C and depression. We report two patients with recurrent hepatitis C after liver transplantation who also developed severe depression. One patient died of multiorgan failure and the other, septicemia caused by Staphylococcus aureus. Both patients had evidence of severe hepatitis C recurrence with features of cholestatic fibrosing hepatitis. We were able to study samples of their central nervous system obtained at autopsy for evidence of HCV replication. The presence of HCV RNA-negative strand, which is the viral replicative form, was determined by strand-specific Tth-based reverse-transcriptase polymerase chain reaction. Viral sequences were compared by means of single-strand conformation polymorphism and direct sequencing. HCV RNA-negative strands were found in subcortical white matter from one patient and cerebral cortex from the other patient. HCV RNA-negative strands amplified from brain tissue differed by several nucleotide substitutions from serum consensus sequences in the 5 untranslated region. These findings support the concept of HCV neuroinvasion, and we speculate that it may provide a biological substrate to neuropsychiatric disorders observed in patients with chronic hepatitis C. P atients with chronic hepatitis C frequently report tiredness, easy fatigability, and depression. Dwight et al 1 reported that 28% of patients with chronic hepatitis C had current depressive disorders. They concluded that disability and fatigue were related more closely to severity of depression than to progression of liver disease. More recently, Forton et al 2 addressed the hypothesis that hepatitis C virus (HCV) itself may affect cerebral function and provide the substrate for the chronic fatigue syndrome frequently associated with HCV infection. The investigators used proton magnetic resonance spectroscopy and showed elevations in choline-creatine ratios in the basal ganglia and white matter of patients with histologically mild hepatitis C that were not present in healthy volunteers and patients with hepatitis B. This elevated ratio was unrelated to hepatic encephalopathy or a history of intravenous drug abuse. The investigators suggested that a biological process underlies extrahepatic symptoms in chronic HCV infection, although they did not speculate on its nature. Furthermore, because HCV has been found to replicate in lymphoid cells and monocyte/ macrophages 3-5 and these cells can enter the central nervous system (CNS), 6 a possibility remains that psychosomatic syndromes observed in patients with HCV infection are related to viral replication in the CNS.We studied two patients with recurrent hepatitis C after cadaveric liver transplantation for end-stage liver disease caused by HCV infection who presented a clinical picture of profound depression. These patients subsequently died,...

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Section: Discussionmentioning

confidence: 99%

“…7,9,10 For the purpose of sequence comparison, nested protocols were used to maximize the yield of PCR product. Amplification of 5Ј UTR was conducted using RT-PCR assay, as previously described.…”

Section: Analysis Of Hcv Quasispeciesmentioning

confidence: 99%

Detection of hepatitis C virus sequences in brain tissue obtained in recurrent hepatitis C after liver transplantation

et al. 2002

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“…Supporting this, HCV replication in lymphoid cells has been shown in HIV-1 positive patients. 32 More recently, Sulkowski et al 33 showed no difference in the risk of death or in the risk of developing a new AIDS-defining illness in patients with and without HCV. Survival was reduced in HCV-infected patients with baseline CD4 cell counts from 50 cells/mm 3 through 200 cells/mm 3 .…”

Section: Discussionmentioning

confidence: 99%

Hepatitis C infection is not associated with systemic HIV‐associated non‐hodgkin's lymphoma: A cohort study

Waters¹,

Stebbing²,

Mandalia³

et al. 2005

Intl Journal of Cancer

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Immunosuppression induced by the human immunodeficiency virus (HIV) increases the risk of developing non-Hodgkin's lymphoma (NHL). As the hepatitis C virus (HCV) has been implicated in the development of B cell lymphomas, we compared the incidence of systemic NHL during HIV infection compared to HIV and HCV co-infection. Of 5,832 individuals studied during the era of highly active anti-retroviral therapy (HAART), 102 patients were diagnosed with systemic NHL. The incidence of systemic NHL was 6.9 of 10 4 patient years during HIV infection compared to 7.1 of 10 4 patient years during HIV alone (p ¼ 0.9). In this immunocompromised patient population, there was no association between HCV infection and an increased risk of lymphoma. ' 2005 Wiley-Liss, Inc.Key words: hepatitis C; HIV; non-Hodgkin's lymphomaThe use of HAART has resulted in marked declines in HIVrelated morbidity and mortality, by mainly reducing the incidence of opportunistic infections 1 High grade B-cell non-Hodgkin's lymphoma (NHL) is an AIDS defining illness, having first been described in association with HIV in the early 1980s. 2 NHL occurs at a greatly increased frequency in HIV-infected populations and despite a reduction in its incidence during the HAART era, it remains the second commonest AIDS defining malignancy after Kaposi's sarcoma. [3][4][5][6][7] Many of the 200 million individuals infected with HCV and the 50 million individuals infected with HIV are co-infected with both viruses. [8][9][10] As well as shared routes of transmission, there are many interactions between these small RNA viruses in which infection is often characterised by parenteral transmission followed by a seroconversion illness and then a long latent period lasting many years. 11 Once established, HIV-1 infection seems to increase the persistence of the hepatitis C virus, the level of HCV RNA and progression of HCV-related disease. [12][13][14][15][16] There are conflicting reports concerning whether HCV infection alters the course of HIV. 17 Some studies before the advent of highly active anti-retroviral therapy (HAART) suggested that survival and progression to AIDS were the same in patients with HCV/HIV co-infection as in those with HIV alone 18,19 whereas others suggested an adverse effect. 13,20 In the pre-HAART era, HCV infection was deemed an irrelevance as it was HIV that affected morbidity and mortality. With the increased life expectancy of individuals with HIV, however, HCV has emerged as a problem that adversely affects survival of individuals with HIV. 8,16,21 HCV is a well-established risk factor in the etiology of hepatocellular carcinomas and of mixed cryoglobulinemia Type II, a condition that can evolve to malignant lymphoma in 8-10% of affected cases. 22 In the non-HIV setting, data from case-case comparisons and case-control studies indicate several-fold higher prevalence of HCV infection (as indicated by the presence of antibodies or HCV RNA) among B cell lymphoma patients compared to control populations. 23 Attempts have been made to evaluate an...

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“…For instance, negative-strand HCV RNA has been identified in a variety of non-hepatic tissues (Table 2), including the pancreas, thyroid, bone marrow, adrenal gland, spleen, lymph node, cervicovaginal fluid, and brain. 29,[67][68][69][70][71][72] Initial studies similarly reported extrahepatic replication of HCV in PBMCs (Table 3). 58,[73][74][75][76][77] However, as the detection assays were not able to adequately differentiate between positive-and negative-strand HCV RNAs, theses results should be interpreted with extreme caution.…”

Section: Evidence For Extrahepatic Replication Of Hcvmentioning

confidence: 99%

Extrahepatic replication of HCV: Insights into clinical manifestations and biological consequences

2006

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Hepatitis C Virus in Lymphoid Cells of Patients Coinfected with Human Immunodeficiency Virus Type 1: Evidence of Active Replication in Monocytes/Macrophages and Lymphocytes

Cited by 207 publications

References 45 publications

Detection of hepatitis C virus sequences in brain tissue obtained in recurrent hepatitis C after liver transplantation

Detection of hepatitis C virus sequences in brain tissue obtained in recurrent hepatitis C after liver transplantation

Hepatitis C infection is not associated with systemic HIV‐associated non‐hodgkin's lymphoma: A cohort study

Extrahepatic replication of HCV: Insights into clinical manifestations and biological consequences

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