Non-A, Non-B Hepatitis Transmission in Chimpanzees: A Project of the Transfusion-Transmitted Viruses Study Group

Hollinger, Blaine; Gitnick, Gary; Aach, Richard D.; Szmuness, Wolf; Mosley, James W.; Stevens, Cladd E.; Peters, Robert L.; Weiner, John M.; Werch, Jochewed; Lander, Jerrold J.

doi:10.1159/000148969

Cited by 111 publications

(31 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…With the advent of serological tests to detect infection by HAV and HBV in the mid-1970s, it was surprising to find that most cases of parenterally-transmitted hepatitis were not in fact due to either virus [4] hence heralding the term, Non-A, Non-B hepatitis (NANBH). Dr. Harvey Alter and other groups then pioneered the use of the chimpanzee as a reliable model for serial passage of NANBH infection from human materials [5,6]. The use of this model provided data indicating the existence of multiple NANBH agents, one of which was shown to cause characteristic membranous tubules within the cytoplasm of infected chimpanzee hepatocytes (the so-called tubule-forming agent (TFA; Ref.…”

Section: Introductionmentioning

confidence: 99%

The long and winding road leading to the identification of the hepatitis C virus

Houghton

2009

Journal of Hepatology

119

View full text Add to dashboard Cite

This review describes work conducted largely in my laboratory at the Chiron Corporation between 1982 and 1989 that led to the identification of the hepatitis C virus (HCV). Key colleagues included Dr. Qui-Lim Choo in my laboratory and Dr. George Kuo also of Chiron as well as my collaborator Dr. Daniel Bradley at the CDC who provided many biological samples from the NANBH chimpanzee model. Numerous molecular approaches were explored including the screening of tens of millions of bacterial cDNA clones derived from these materials. While this early genomics approach resulted in the identification of many host gene activities associated with NANBH, no genes of proven infectious etiology could be identified. A separate avenue of our research led to the molecular characterization of the complete hepatitis delta viral genome but unfortunately, this could not be used as a molecular handle for HCV. Largely following input from Dr. Kuo, I initiated a blind cDNA immunoscreening approach involving the large-scale screening of bacterial proteomic cDNA libraries derived from NANBH-infectious chimpanzee materials (prior to the development of PCR technology) using sera from NANBH patients as a presumptive source of viral antibodies. Eventually, this novel approach to identifying agents of infectious etiology led to the isolation of a single small cDNA clone that was proven to be derived from the HCV genome using various molecular and serological criteria. This discovery has facilitated the development of effective diagnostics, blood screening tests and the elucidation of promising drug and vaccine targets to control this global pathogen.

show abstract

Section: Introductionmentioning

confidence: 99%

The long and winding road leading to the identification of the hepatitis C virus

Houghton

2009

Journal of Hepatology

119

View full text Add to dashboard Cite

show abstract

“…In an effort to study the various aspects of this serious human disease, chimpanzees have been shown to be suitable experimental models that are susceptible to NANB hepatitis virus infection (2,3,16,17,24). The reagent materials (NANB antigen) obtained from experimental animals have been used in conjunction with presumed convalescent human antibody to NANB in attempts to demonstrate immunological reactions with specificity for NANB hepatitis antigen.…”

mentioning

confidence: 99%

Detection of non-A, non-B hepatitis antigen by immunocytochemical staining.

Burk¹,

Oefinger²,

Dreesman³

1984

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Liver tissue obtained from a chimpanzee during the acute phase of an experimental non-A, non-B (NANB) hepatitis virus infection was studied by a sensitive immunocytochemical staining procedure for the presence of NANB viral antigens. Initial investigations were conducted with a model system of hepatitis B virus (HBV) antigens for purposes of comparing two immunocytochemical staining methods. Of these two procedures, an immunoperoxidase procedure, utilizing an avidin-biotinylated enzyme complex, was at least 40-fold more sensitive than a conventional immunoperoxidase technique for the detection of HBV-specific tissue antigens. Utilization of the avidin-biotin-amplified immunoperoxidase staining procedure, in conjunction with four primary convalescent antisera obtained from NANB hepatitis-implicated donors, resulted in the observation of NANB virus-associated antigen in the cytoplasm of hepatocytes from an infected chimpanzee liver. These same human antisera were not reactive with a number of uninfected control cells nor with cells infected with HBV, hepatitis A virus, or cytomegalovirus. Preincubation of one of these convalescent NANB sera, or IgG derived thereof, with an acute-phase serum obtained from a NANB hepatitis virus-infected chimpanzee abolished the antibody reactivity. We conclude from these observations that selected convalescent sera from NANB hepatitis virus-infected patients contain low levels of antibody that specifically react with a cytoplasmic antigen associated with NANB virus-infected hepatocytes.Non-A, non-B (NANB) hepatitis has been recognized as a virus-induced disease that is distinct from other forms of viral-associated liver diseases, including hepatitis A virus (HAV) and hepatitis B virus (HBV), and the hepatitides induced by cytomegalovirus or Epstein-Barr virus (1-3). Clinical (19,20). In addition, studies in chimpanzees involving the chronic sequelae associated with NANB hepatitis now appear to be more serious than chronic disease developments arising from HBV infection (21-23).In an effort to study the various aspects of this serious human disease, chimpanzees have been shown to be suitable experimental models that are susceptible to NANB hepatitis virus infection (2,3,16,17,24). The reagent materials (NANB antigen) obtained from experimental animals have been used in conjunction with presumed convalescent human antibody to NANB in attempts to demonstrate immunological reactions with specificity for NANB hepatitis antigen. The present study describes a highly sensitive immunocytochemical procedure that utilizes NANB-infected chimpanzee liver expressing NANB antigen and human convalescent sera containing anti-NANB.Control and specificity studies are described herein that provide convincing evidence for the specificity of the NANB hepatitis virus immunocytochemical reactivity. MATERIALS AND METHODSChimpanzee Materials. Liver biopsy material was obtained from four chimpanzees (nos. 90, 92, 94, and 159) infected with human plasma containing infectious NANB hepatitis virus (1...

show abstract

“…The existence of the NANB hepatitis viruses became evident from epidemiological studies [Alter et al, 1978;Tabor et al, 19781 as well as by inoculation of human volunteers [Hoofnagle et al, 19771 and chimpanzees [Alter et al, 1978;Tabor et al, 1978;Hollinger et al, 1978;Bradley et al, 19801. Further cross-challenge experiments in chimpanzees indicated that there are, at least, two parenterally transmitted viruses [Shimizu et al, 1979;Bradley et al, 1980;Hollinger et al, 1980;Yoshizawa et al, 19811.…”

Section: Introductionmentioning

confidence: 99%

Prevalence of a non‐A, non‐B‐associated antigen/antibody system detected by radioimmunoassay in acute and chronic liver disease

Luo

Karayiannis

Burns

et al. 1983

Journal of Medical Virology

View full text Add to dashboard Cite

An antigen/antibody system associated with one form of parenterally transmitted non-A, non-B (NANB) hepatitis has been identified by solid-phase radioimmunoassay (RIA). The antigen is found in 3% of normal subjects and in increased frequency in patients with haemophilia, renal homograft recipients, homosexual men, prostitutes, drug addicts, and patients with chronic hepatitis B virus (HBV) infection. The antigen was found in normal frequency in patients with acute hepatitis A and B, sporadic NANB hepatitis (nondrug addicts), autoimmune and alcohol-induced chronic liver disease, and primary biliary cirrhosis.

show abstract

Non-A, Non-B Hepatitis Transmission in Chimpanzees: A Project of the Transfusion-Transmitted Viruses Study Group

Cited by 111 publications

References 5 publications

The long and winding road leading to the identification of the hepatitis C virus

The long and winding road leading to the identification of the hepatitis C virus

Detection of non-A, non-B hepatitis antigen by immunocytochemical staining.

Prevalence of a non‐A, non‐B‐associated antigen/antibody system detected by radioimmunoassay in acute and chronic liver disease

Contact Info

Product

Resources

About