Detection of hepatitis C virus (HCV) RNA sequences in liver tissue by in situ hybridization

Lamas, Eugenia; Baccarini, Paola; Housset, Chantal; Kremsdorf, Dina; Bréchot, Christian

doi:10.1016/s0168-8278(05)80119-9

Cited by 57 publications

(28 citation statements)

References 5 publications

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“…Identification of HCV-infected cells within the liver has been difficult to demonstrate with conflicting reports, and this makes viral production rates difficult to ascertain. [27][28][29] A recent report by Gale and colleagues 30 demonstrated focal areas of infected cells within the liver that were consistent with our in vitro observations. 30 Plasma from HCV-infected individuals has been reported to infect chimpanzees 31 and mice bearing chimeric human livers, 32 and this suggests that transmission between hosts is most likely mediated via cell-free virus.…”

Section: Discussionsupporting

confidence: 90%

Hepatitis C virus cell-cell transmission in hepatoma cells in the presence of neutralizing antibodies

et al. 2008

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H epatitis C virus (HCV) has emerged as the major etiological agent of liver disease. Approximately 170 million individuals are infected worldwide, and the majority are at risk for developing serious progressive liver disease, with HCV being the leading indication for liver transplantation. The HCV single-stranded RNA genome encodes a single polyprotein, which is cleaved by viral and cellular proteases to produce the structural proteins; core E1 and E2 and nonstructural proteins; p7, NS2, NS3, NS4A, NS4B, NS5A, and NS5B. The only approved treatment for HCV infection is interferon-␣ in combination with ribavirin, which is toxic and only effective in 50% of individuals with genotype I infections. Clearly, there is a need for more effective therapies and for the development of prophylactic and/or therapeutic vaccines.Cellular and humoral responses are generated during acute infection, but they are insufficient to achieve viral clearance in the majority of individuals, with approximately 60%-80% of new infections becoming persistent. 1,2 Neutralizing antibody (nAb) responses often provide the first-line adaptive defense against infection by limiting virus spread. However, little is known about the impact of the humoral immune response on HCV pathobiology. Serum antibodies (Abs) from chronically HCVinfected individuals demonstrate broadly reactive neutralizing properties in vitro and yet fail to control viral infection in vivo. [3][4][5] The reasons for their lack of effect are poorly understood. HCV may escape neutralization by

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Section: Discussionsupporting

confidence: 90%

Hepatitis C virus cell-cell transmission in hepatoma cells in the presence of neutralizing antibodies

et al. 2008

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“…3,4 In situ staining techniques have clarified some aspects of the cell tropism of Flaviviridae, such as the yellow fever virus, 5,6 the Dengue fever virus, 6,7 and many others. Conversely, the wealth of studies which have analyzed the tropism of HCV have often produced conflicting reports [8][9][10][11][12][13][14] and have been met with skepticism, as reflected by several critical review articles. 15,16 Although HCV infection of hepatocytes has been demonstrated convincingly by in situ hybridization and immunohistochemistry, the localization of HCV in both peripheral blood mononuclear cells (PBMC) and bone marrow cells has repeatedly been questioned, although similar techniques, as well as the strand-specific reverse-transcriptase polymerase chain reaction (RT-PCR) amplification, have been used.…”

mentioning

confidence: 99%

“…A more sensitive in situ PCR analysis, using fluorescent primers, increased the percentage up to a maximum of 8.1% of the total number of cells. 35 Also mononuclear cells infiltrating the liver have reportedly been infected by HCV, [8][9][10]12 but these data are contradicted by most other groups who have applied similar techniques. 16 The presence of HCV has been evaluated in several other extrahepatic compartments.…”

mentioning

confidence: 99%

Does the hepatitis C virus replicate in cells of the hematopoietic lineage?

Negro

Levrero

1998

Hepatology

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“…In situ hybridization studies of the genomic RNA have been revealed in chimpanzee hepatocytes by immunohistochemical reaction (Negro et al 1992). In addition, some reports described the detection of HCV RNA minus-strand in human liver by in situ hybridization technique also, not showing the ultrastructural localization of HCV RNA (Lamas et al 1992, Nouri-Aria et al 1993, Gastaldi et al 1995, Sansonno et al 1997, Chang et al 2000. Shimizu et al (1996) observed a positive reaction in the liver biopsies of HCV infected chimpanzees, using the immunofluorescence technique with anti-HCV envelope protein.…”

Section: Virus Reviews and Research 14 Nr 1 2009mentioning

confidence: 99%

Ultrastructural Localization of Hepatitis C Virus Positive and Negative Strand Rna and Proteins in Hepatocytes of a Rhesus Monkey (Macaca Mulatta)

Majerowicz¹,

Grief²,

Pinto³

et al. 2009

VR&R

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Morphological alterations of the liver from rhesus macaque (Macaca mulatta)experimentally infected with hepatitis C virus (HCV) were analyzed using electron microscopy. The localization of viral RNA and proteins inside hepatocytes was demonstrated using in situ hybridization and immunoelectron microscopy techniques. The animals were inoculated by different routes. The infection was successful only by use of the intrasplenic approach to HCV infected autogenic hepatocyte transplant. The inoculum used to infect the hepatocytes was characterized as genotype 3 with 10 7 RNA copies/mL. In situ hybridization was performed using a complementary negative and positive strand probe made with the specific primer. Despite that the level of HCV infection was considered to be low, we were able to detect and localize viral positive and negative RNA strands and viral proteins in altered membranes of the rough endoplasmic reticulum in infected liver cells, showing evidence of viral replication in vivo.

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Detection of hepatitis C virus (HCV) RNA sequences in liver tissue by in situ hybridization

Cited by 57 publications

References 5 publications

Hepatitis C virus cell-cell transmission in hepatoma cells in the presence of neutralizing antibodies

Hepatitis C virus cell-cell transmission in hepatoma cells in the presence of neutralizing antibodies

Does the hepatitis C virus replicate in cells of the hematopoietic lineage?

Ultrastructural Localization of Hepatitis C Virus Positive and Negative Strand Rna and Proteins in Hepatocytes of a Rhesus Monkey (Macaca Mulatta)

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