Hepatitis C Virus Infection in Post-Transfusion Hepatitis

Aach, Richard D.; Stevens, Cladd E.; Hollinger, F. Blaine; Mosley, James W.; Peterson, David A.; Taylor, Patricia E.; Johnson, Rhonda G.; Barbosa, Luiz H.; Nemo, George J.

doi:10.1056/nejm199111073251901

Cited by 485 publications

(34 citation statements)

References 15 publications

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“…1 is the major cause of non-A, non-B hepatitis worldwide (1,2), which often leads to liver cirrhosis and hepatocellular carcinoma (3)(4)(5). HCV is an enveloped positive-sense RNA virus of the Flaviviridae family (6).…”

Section: Hepatitis C Virus (Hcv)mentioning

confidence: 99%

Nonstructural 5A Protein of Hepatitis C Virus Modulates Tumor Necrosis Factor α-stimulated Nuclear Factor κB Activation

Park

Choi

Lee

et al. 2002

Journal of Biological Chemistry

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The hepatitis C virus nonstructural protein 5A (NS5A) is a multifunctional phosphoprotein that leads to pleiotropic responses, in part by regulating cell growth and cellular signaling pathways. Here we show that overexpression of NS5A inhibits tumor necrosis factor (TNF)-␣-induced nuclear factor B (NF-B) activation in HEK293 cells, as determined by luciferase reporter gene expression and by electrophoretic mobility shift assay. When overexpressed, NS5A cannot inhibit the recruitment of TNF receptor-associated factor 2 (TRAF2) and IB kinase (IKK)␤ into the TNF receptor 1-TNF receptor-associated death domain complex. In contrast, NS5A is a part of the TNF receptor 1 signaling complex. NF-B activation by TNF receptor-associated death domain and TRAF2 was inhibited by NS5A, whereas MEKK1 and IKK␤-dependent NF-B activation was not affected, suggesting that NS5A may inhibit NF-B activation signaled by TRAF2. Coimmunoprecipitation and colocalization of NS5A and TRAF2 expressed in vivo provide compelling evidence that NS5A directly interacts with TRAF2. This interaction was mapped to the middle onethird (amino acids 148 -301) of NS5A and the TRAF domain of TRAF2. Our findings suggest a possible molecular mechanism that could explain the ability of NS5A to negatively regulate TNF-␣-induced NF-B activation.

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Section: Hepatitis C Virus (Hcv)mentioning

confidence: 99%

Nonstructural 5A Protein of Hepatitis C Virus Modulates Tumor Necrosis Factor α-stimulated Nuclear Factor κB Activation

Park

Choi

Lee

et al. 2002

Journal of Biological Chemistry

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“…HCV is now infrequently transmitted by transfusion beonly about 30% of all newly acquired HCV infections. 3,4 cause of screening tests that exclude infectious donors, and Thus, after correcting for asymptomatic infections, the estithe current risk of transfusion-associated HCV infection is estimated at .01% to .001% per unit transfused. 8,9 In addition, the viral inactivation of clotting factor concentrates has virtu- Other persons at risk as a result of exposure to infectious although such transmission has been reported from other blood are health-care workers and hemodialysis patients, ac-countries.…”

Section: Virus Infectionmentioning

confidence: 99%

Epidemiology of hepatitis C

1997

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In the United States, the annual number of newly acquired acute hepatitis C virus (HCV) infections has declined from an estimated 180,000 in the mid 1980s to an estimated 28,000 in 1995. Approximately 25% to 30% of these infections are clinically apparent cases that are sufficiently symptomatic to gain medical attention. Deaths from fulminant hepatitis C are rare. The prevalence of antibody to HCV (anti‐ HCV) in the general population of the United States is 1.8%, corresponding to an estimated 3.9 million Americans infected with HCV, and an estimated 8,000 to 10,000 deaths each year result from HCV‐ associated chronic liver disease. HCV infection affects persons of all ages, but most acute cases of hepatitis C and the highest prevalence of anti‐HCV are found among young adults. The highest proportion both of incident cases and prevalent infections is among whites, but the highest incidence and prevalence rates are among non‐white racial/ethnic groups. In the past, transfusion of blood and blood products was an important source of HCV transmission, but currently, high‐risk drug and sexual exposures account for most HCV transmission. Although the incidence of acute hepatitis C has declined, there is a large reservoir of chronically infected Americans who can serve as a source of transmission to others and who are at risk of the severe consequences of chronic liver disease.

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“…Hepatitis C Virus (HCV) 1 is the major cause of transfusionand community-acquired non-A, non-B hepatitis (1)(2)(3), often leading to cirrhosis of the liver, hepatocellular carcinoma (3)(4)(5), and some autoimmune diseases (6 -10). HCV is an enveloped, single-stranded, positive-sensed RNA virus.…”

mentioning

confidence: 99%

“…: 323-442-1748; Fax: 323-342-9555; E-mail: michlai@hsc.usc.edu. 1 The abbreviations used are: HCV, hepatitis C virus; hnRNP K, heterogeneous nuclear ribonucleoprotein K; GST, glutathione S-transferase; PCR, polymerase chain reaction; GFP, green fluorescent protein; CAT, chloramphenicol acetyltransferase; PBS, phosphate-buffered saline; PAGE, polyacrylamide gel electrophoresis; aa, amino acids; TK, thymidine kinase. grown in Dulbecco's modified Eagle's medium (Irvine Scientific) supplemented with nonessential amino acids (Life Technologies, Inc.) and 10% fetal bovine serum.…”

mentioning

confidence: 99%

Hepatitis C Virus Core Protein Interacts with Heterogeneous Nuclear Ribonucleoprotein K

Hsieh¹,

Matsumoto²,

Chou³

et al. 1998

Journal of Biological Chemistry

139

117

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Hepatitis C virus (HCV) core protein, a component of viral nucleocapsid, has been shown to modulate cellular and viral promoter activities. To identify potential cellular targets for HCV core protein, a human liver cDNA library was screened for core-interacting proteins using the yeast two-hybrid system. Among the proteins identified was heterogeneous nuclear ribonucleoprotein K (hnRNP K), which has been demonstrated to be a transcriptional regulator. The interaction of HCV core protein with hnRNP K was confirmed by glutathione Stransferase fusion protein binding assay, proteinprotein blotting assay, and coimmunoprecipitation in vitro and in vivo. Additionally, these two proteins were shown to be partially colocalized in the nucleus. The hnRNP K-binding site in HCV core protein was mapped to the region from amino acid residues 25-91, a hydrophilic area near the N terminus. The HCV core proteinbinding domain was located within amino acid residues 250 to 392, which contain the three proline-rich domains, of hnRNP K. Furthermore, HCV core protein relieved the suppression effect of hnRNP K on the activity of the human thymidine kinase gene promoter. The specific binding of HCV core protein to hnRNP K suggests that multiple functions of hnRNP K may be disrupted by the core protein during HCV infection and thus explains, in part, the pathogenesis of HCV.

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Hepatitis C Virus Infection in Post-Transfusion Hepatitis

Cited by 485 publications

References 15 publications

Nonstructural 5A Protein of Hepatitis C Virus Modulates Tumor Necrosis Factor α-stimulated Nuclear Factor κB Activation

Nonstructural 5A Protein of Hepatitis C Virus Modulates Tumor Necrosis Factor α-stimulated Nuclear Factor κB Activation

Epidemiology of hepatitis C

Hepatitis C Virus Core Protein Interacts with Heterogeneous Nuclear Ribonucleoprotein K

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