[The virus isolated from patient TT (TTV): still an orphan 2 years after its discovery]. / Le virus isolé du patient TT (TTV): toujours orphelin deux années après sa découverte.

TTV is the acronym for a virus isolated two years ago from a patient whose initials were T.T. It is a naked virus probably belonging to the Circoviridae family. TTV has a particle size of 30-50 nm and possesses a single-strand circular DNA. Epidemiologic data are derived from studies looking for the viral DNA by the polymerase chain reaction (PCR). Important differences between early and recent studies appear to be due to the use of PCR assays based on primers located in different regions of the genome. Based on the most recent studies, the prevalence of TTV infections seems very high in the general population. TTV is present in the feces and would be transmitted through the fecal-oral route. It appears to be a ubiquitous virus, also present in various animal species, from chickens to chimpanzees. No association to any pathology has been identified so far, and TTV infection does not have a significant effect on liver disease.

Expression of infectious viral particles by primary chimpanzee hepatocytes isolated during the acute phase of non-A, non-B hepatitis.

Liver wedge biopsies were obtained from chimpanzees during the acute phase of experimental non-A, non-B hepatitis infections. Primary chimpanzee hepatocytes were maintained for over 4 weeks in vitro with a serum-free medium supplemented with growth factors and hormones. The de novo synthesis and secretion of plasma proteins characteristic for differentiated primate hepatocytes were sustained under these culture conditions. Immunocytochemical staining for a non-A, non-B hepatitis-associated antigen revealed expression of this cytoplasmic marker during the culture period, indicating a persistence of the infection in vitro. Tissue culture medium derived from the hepatocyte cultures was used to inoculate a nonimmune chimpanzee. The animal subsequently displayed an increase in the serum levels of alanine aminotransferase, the development of histopathologic alterations indicative of viral hepatitis, and the appearance of liver cell cytoplasmic tubules diagnostic for non-A, non-B hepatitis. Concentrated tissue culture medium examined by electron microscopy contained virus-like particles with an average diameter of 39-46 nm, which exhibited an envelope and inner 37-nm core structure.

Intracytoplasmic inclusions in human hepatocytes in non-A, non-B hepatitis: an ultrastructural study.

An ultrastructural study was carried out on 114 liver biopsies obtained for diagnostic purposes from patients with various pathological disorders of the liver including hepatitis B-related liver disease, non-A, non-B hepatitis, alcoholic liver disease, fatty change, and cryptogenic cirrhosis. The opportunity was taken to evaluate the significance of intracytoplasmic crystalline structures found in the hepatocytes of nine patients with a variety of liver disorders. The cytoplasmic inclusions varied in size up to 2 microns in length and shape and were not limited by membranes. The presence of these inclusions cannot, however, be correlated either specifically with non-A, non-B hepatitis or with other known nonviral liver disease. The functional, physiological, and pathological significance of the crystalline structures remain to be elucidated.

Experimental infection of chimpanzees with antihemophilic (factor VIII) materials: recovery of virus-like particles associated with non-A, non-B hepatitis.

Non-A, non-B viral hepatitis was transmitted to four colony-born chimpanzees by infusion of three lots of antihemophilic factor (factor VIII) implicated in the transmission of non-A, non-B hepatitis to two human recipients. All four inoculated animals showed histopathological evidence of viral hepatitis, and all demonstrated significant ALT elevations between seven and one-half weeks after inoculation. Acute-phase plasma from one of the infected chimpanzees (no. 771) was shown to induce non-A, non-B hepatitis in two other chimpanzees approximately three weeks after their inoculation. In addition, an acute-phase open liver wedge biopsy obtained from animal no. 771 was processed and examined by immune electron microscopy (IEM) for virus-like particles with convalescent serum from a serologically confirmed case of non-A, non-B hepatitis. Twenty-five to 30 nm (mean = 27 nm) diameter virus-like particles that were either "full" or "empty" were identified in this liver preparation by IEM. Two additional chimpanzees inoculated with a cesium chloride gradient fraction of an isopycnically banded liver homogenate (animal no. 771) also developed elevated ALT activity two to two and one-half weeks later. Our findings have experimentally verified that commercially produced factor VIII materials can induce non-A, non-B hepatitis in champanzees and that the disease can be subpassaged in these animals by inoculation of either acute-phase plasma or liver. These results also provide evidence for the association of 27 nm-diameter virus-like particles with non-A, non-B viral hepatitis.

Incidence and nature of cytoplasmic hepatitis B antigen in hepatocytes.

Hepatitis B antigen (HB Ag) in the hepatocytic cytoplasm is detected by immunofluorescence after reaction with fluoresceinated antiserum to HB Ag or by electron microscopy as numerous 20- to 30-nm. tubular and circular structures in dilated cisternae of excess endoplasmic reticulum. On light microscopy, these hepatocytes can be recognized because their cytoplasm has a ground-glass appearance and stains with Gomori's aldehyde fuchsin. Aldehyde fuchsin-positive ground-glass hepatocytes were detected in all 14 asymptomatic carriers of HB Ag and in 16 of 60 HB Ag-seropositive patients with chronic hepatitis, but not in HB Ag-seropositive acute viral hepatitis or in various other HB Ag-seronegative liver diseases. These cells are helpful in identifying on light microscopy HB Ag carriers and a portion of patients with HB Ag-positive chronic hepatitis. Nuclear HB Ag did not stain with aldehyde fuchsin. Nucleic acids were not detected in the ground-glass cytoplasm by special stains at the light or electron microscopic level. We suggest that the tubular and circular structures in the hepatocytic cytoplasm are coat material of the hepatitis B virus or virally coded host cell reaction product rather than the complete hepatitis B virus.