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Nine of 15 specimens of human origin thought to contain non-A, non-B hepatitis agents caused hepatitis in recipient chimpanzees. Two have been further characterized. One inoculum, designated strain F, has been reported to produce unique cytoplasmic changes detected by electron microscopyin liverbiopsy specimens;the other, strain H, produced distinctive nuclear changes. It is not yet clear whether these two changes result from infection by different agents; they have been useful markers of non-A, non-B hepatitis in chimpanzees. Strain F was seriallypassaged sixtimes in chimpanzees, and the infectivity titer of the strain F plasma wasestimated to be <102/ml. Strain H had an infectivity titer in chimpanzees of at least 106/ml Both the strain F and strain H agents have been successfully transmitted and serially passaged in marmosets. Although hepatitis was detected in a lower percentage of marmosets than chimpanzeesgiven either the strain F or H inoculum, the infectivity titer of the strain H agent appeared to be ~ 108 marmoset infectious doses/ml. [ABSTRACT FROM PUBLISHER]

SEN virus (SENV) is a recently discovered group of DNA viruses whose members (SENV-D and SENV-H) are linked to posttransfusion hepatitis. Of 397 injection drug users (IDUs) in Baltimore, Maryland, SENV-D infection was detected by polymerase chain reaction in serum samples from 130 (32.7%) and SENV-H infection in 149 (37.5%). Of 41 IDUs in whom SENV-D DNA was initially detected, retesting for viral persistence a median of 9.3 years later detected SENV-D in 25 (61.0%), whereas SENV-H was detected on retesting in only 14 (26.9%) of 52 IDUs in whom the virus was originally found. Reinfection was apparent (>5% nucleotide difference) in 77.8% of IDUs who repeatedly tested positive for SENV-D DNA and in 55.6% of those who repeatedly tested positive for SENV-H DNA. Among Baltimore IDUs, SENV-D and SENV-H infections are common and dynamic, including both viral clearance and reinfection. The clinical significance of SENV infection in this setting remains unknown.

There is a strong association between 2 SEN virus (SENV) variants (SENV-D and SENV-H) and transfusion-associated non-A-E hepatitis. In total, 200 subjects from a Japanese region where hepatitis C virus (HCV) is highly endemic and 194 persons from a contiguous area where HCV is not endemic were tested for SENV-D and SENV-H DNA by polymerase chain reaction. SENV DNA was detected equally in subjects from each area (56% prevalence in the area of high endemicity vs. 61% in the nonendemic area). Age-specific prevalence of SENV was similar to that of TT virus, with equal distribution at all ages in both areas; HCV was predominant in the elderly population. Alanine aminotransferase levels were significantly associated with HCV viremia but not with SENV viremia. SENV is a common infection that appears to have transmission routes and age-related prevalence that are distinct from those of HCV. No evidence was found that SENV caused hepatitis or worsened the course of hepatitis C.

The existence of the newly discovered SEN virus (SENV) was investigated in 379 Japanese patients with liver diseases and in 277 blood donors, to determine whether SENV is associated with non-A-E hepatitis. SENV DNA was detected by seminested polymerase chain reaction, with primers directed to 2 SENV strains: SENV-H and SENV-D. SENV was detected in 7 (32%) of 22 patients with fulminant hepatitis, in 15 (17%) of 86 patients with acute hepatitis, in 38 (27%) of 139 patients with chronic hepatitis, in 29 (31%) of 93 patients with liver cirrhosis, in 5 (33%) of 15 patients with autoimmune hepatitis, in 11 (46%) of 24 patients with primary biliary cirrhosis, and in 27 blood donors (10%). Infection occurred more frequently in patients with liver diseases than in blood donors; however, there were no significant differences in SENV-positive rates between patients with non-A-C hepatitis and those with acute or chronic hepatitis due to known hepatitis virus or nonviral liver disease. This study did not suggest SENV as a possible causative agent of non-A-C hepatitis.

A new group of transmissible single-stranded (ss) DNA viruses (SENV) distantly related to the large TT virus (TTV) family was recently identified. Eight different SENV isolates have been found, some with an association with posttransfusion hepatitis. A phylogenetic analysis of near-complete open-reading frame 1, including conserved motifs and excluding recombinant regions, was performed. The analysis used TTV-like minivirus as an outgroup, to determine a root of the phylogenetic tree, and compared 8 SENV isolates, 6 prototype TTV isolates, and 7 TTV variants (including SANBAN, TUS01, PMV, and YONBAN). Four distinct clusters separated by a bootstrap value of 100% were observed. YONBAN isolates formed a distinct outer group, representing the earliest recognized phylogenetic divergence (group 1). Prototype TTV formed group 2, PMV formed group 3, and SENV, SANBAN, and TUS01 isolates formed group 4, the most recently evolved group. This taxonomic classification suggests that these circular ssDNA viruses probably evolved from a common ancestor virus.

Serologic, biochemical, and molecular analyses were used to study hepatitis G virus (HGV), antibody to the HGV envelope protein (anti-E2), risk factors, clinical significance, and the impact of HGV on coexistent hepatitis C virus (HCV). Among 329 donors with confirmed HCV infection, 12% were HGV RNA-positive and 44% were anti-E2-positive (total exposure, 56%). HGV RNA and anti-E2 were mutually exclusive except in 9 donors (1.5%); 8 of 9 subsequently lost HGV RNA but anti-E2 persisted. HGV had little impact on alanine aminotransferase, aspartate aminotransferase, or gamma-glutamyl transpeptidase in donors with HGV infection alone or those coinfected with HCV. A multivariate analysis showed that intravenous drug abuse was the leading risk factor for HGV transmission, followed by blood transfusion, snorting cocaine, imprisonment, and a history of sexually transmitted diseases. In summary, HGV and HCV infections were frequently associated and shared common parenteral risk factors; HGV did not appear to cause hepatitis or to worsen the course of coexistent hepatitis C.

GB virus C (GBV-C) RNA and envelope antibody were assessed in a median of 4 samples collected over 6.5 years among injection drug users (IDUs). A marker of GBV-C infection was detected in 110 (94.8%) of 116 IDUs. GBV-C RNA was detected at all visits in 32, was never detected in 70, was acquired in 7, and was cleared in 8. The odds of detecting anti-GBV-C were 103-fold higher in participants without detectable RNA (64 of 70) than in IDUs with persistent RNA (3 of 32; P < 10(-7)). Anti-GBV-C was detected in all 8 instances of RNA clearance. GBV-C RNA never reappeared once it was cleared, and there were no new GBV-C infections among 61 anti-GBV-C-positive IDUs observed for 382 person-years, though all had ongoing drug use. Studies using RNA testing alone may significantly underestimate the occurrence of GBV-C infection. Anti-GBV-C is highly associated with viral clearance and protection from reinfection.

To assess the persistence of hepatitis G virus (HGV) infection and its association with liver disease, HGV RNA was assessed in the most recent serum sample for 246 long-term injecting drug users (IDUs) and in prior specimens for those found HGV RNA-positive. HGV RNA was detected at the most recent visit in 38 (15.4%). For 31 (82%), HGV RNA was also found at all prior visits occurring a median of 6.1 years earlier. HGV-positive IDUs were younger and had fewer years of drug use, suggesting that HGV RNA had previously been cleared. Serial samples from 29 short-term IDUs were then assessed. HGV RNA was detected in 9 (31%) of 29 short-term IDUs, and 5 (56%) of the 9 HGV infections cleared. No differences were detected in serum levels of liver-related enzymes among HGV RNA-positive and -negative participants (P > .20). HGV infection is not associated with hepatic inflammation. HGV clearance occurs after many acute infections but uncommonly in persons who remain RNA-positive years after exposure.