Clinical-liver, pancreas, and biliary tractProductive Replication of Hepatitis C Virus in Perihepatic Lymph Nodes In Vivo: Implications of HCV Lymphotropism
Section snippets
Patients
Twenty consecutive patients with HCV genotype 1 infection and end-stage liver disease were recruited and consented via human subjects–approved protocol. Lymph node biopsy specimens were taken at the time of liver transplantation and immediately snap frozen in ornithine carbamyl transferase (OCT) buffer. Lymph node biopsy specimens were also submitted for histologic evaluation. Twenty negative control lymph node biopsy specimens snap frozen in OCT were obtained from the University of Washington
Characterization of Positive and Negative Control Cell Lines for ISH and ICC Experiments
Permanent cell lines expressing subgenomic regions of HCV sense and antisense RNAs were established from genotypes 1a and 1b clinical isolates for use as positive and negative controls in our strand-specific ISH assay. Figure 1A, 1C, 1E, and 1G illustrates positive staining of plus- and minus-strand HCV RNA expressed in HeLa cells using probes of opposite strand polarity and same genotype. Red punctate signals were evenly distributed throughout the cell cytoplasm, with occasional signal over
Discussion
The question of whether or not HCV is capable of replication in hematopoietic tissues remains controversial, despite a large number of published studies on the topic. Hematopoietic reservoirs of HCV infection could potentially play an important role in viral persistence through mechanisms such as immune escape and viral modulation of host immune responses. From a clinical perspective, hematopoietic infection may help explain the diverse clinical biology of chronic hepatitis C, including the
References (36)
- et al.
Autoimmunity and extrahepatic manifestations in hepatitis C virus infection
J Hepatol
(1999) - et al.
Molecular biology of flaviviruses
Adv Virus Res
(2003) - et al.
Susceptibility of human T-lymphotropic virus type I infected cell line MT-2 to hepatitis C virus infection
Biochem Biophys Res Commun
(1995) - et al.
Replication of hepatitis C virus in B lymphocytes (CD19+)
Blood
(1999) - et al.
Human immunodeficiency virus facilitates infection/replication of hepatitis C virus in native human macrophages
Blood
(2004) - et al.
In vivo tropism of hepatitis C virus genomic sequences in hematopoietic cellsinfluence of viral load, viral genotype, and cell phenotype
Blood
(1998) - et al.
Effect of ribavirin on hepatitis C viral kinetics in patients treated with pegylated interferon
Hepatology
(2003) - et al.
Ultrasound-detected abdominal lymphadenopathy in chronic hepatitis Chigh frequency and relationship with viremia
J Hepatol
(1997) - et al.
Perihepatic lymph nodes and antiviral response in chronic HCV-associated hepatitis
Ultrasound Med Biol
(2004) - et al.
Prevalence of hepatitis C virus infection in patients with lymphoproliferative disorders
Blood
(1996)
HCV and non-Hodgkin lymphoma
Lancet
Hepatitis C virus and B-cell non-Hodgkin lymphomasan Italian multicenter case-control study
Blood
Hepatitis C virus infection in patients with non-Hodgkin lymphoma in Thailand
Blood
Hepatitis C virus infection in patients with overt B-cell non-Hodgkin’s lymphoma in a French center
Blood
45-year follow-up of hepatitis C virus infection in healthy young adults
Ann Intern Med
Infection of a chimpanzee with hepatitis C virus grown in cell culture
J Gen Virol
Establishment of B-cell lymphoma cell lines persistently infected with hepatitis C virus in vivo and in vitrothe apoptotic effects of virus infection
J Virol
Lack of detection of negative-strand hepatitis C virus RNA in peripheral blood mononuclear cells and other extrahepatic tissues by the highly strand-specific rTth reverse transcriptase PCR
J Virol
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Supported by National Institutes of Health grants 61-0311, 61-2154, and 62-2845.