Unidentified virus-like particles are detected in plasmas with elevated ALT levels: are they significant of etiological agent(s) of non-B, non-C hepatitis?
GB virus C (GBV-C) and hepatitis G virus (HGV) have been proposed as new viruses etiologically implicated in non-B, non-C hepatitis, but the morphology of these particular virus particles is still unknown, and most cases of non-A to E hepatitis do not relate to their infections. We tried to visualize virus-like particles (VLPs) in plasma samples from hepatitis B surface antigen- and antibody to hepatitis C virus (HCV)-negative blood donors with elevated alanine aminotransferase (ALT), and examined the association of the virus-like particles and the genomes of parenterally transmissible GBV-C/HGV. Twenty-three plasma samples, 13 with elevated ALT levels and 10 with normal ALT values, from blood donors without infections of hepatitis B virus (HBV) and HCV, were subjected to a 20%-60% sucrose density gradient centrifugation, and virus-like particles were observed by electron microscopy. GBV-C/HGV RNAs in the plasmas were tested. Virus-like particles were found in the fractions with densities of 1.15-1.16 g/ml from 12 of 13 (92.3%) plasmas with elevated ALT levels and 1 of 10 (10%) normal controls. The ultrastructural morphology of visualized VLPs was pleomorphic in size and appearance; the majority of the VLPs were 50- to 80-nm spherical particles with a 35- to 45-nm inner core and 9- to 12-nm-long surface spike-like projections. Rodlike VLPs 50-70 nm in diameter with a length of 110-160 nm were also observed in the same samples. The incidence of detection of the circulating VLPs was significantly (P < 0.001) related to elevated ALT levels, but GBV-C/HGV RNAs were detected in none of the plasmas containing the virus-like particles. Spherical VLPs are detected in HBV- and HCV-negative plasmas significantly correlated with the elevation of ALT, suggesting that they are implicated in non-B, non-C hepatitis.
Kaito
Masahiko
M
Department of Gastroenterology and Hepatology, Division of Clinical Medicine and Biomedical Science, Institute of Medical Science, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan. kaitoma@clin.medic.mie-u.ac.jp
Tanaka
Hideaki
H
Horiike
Shinichiro
S
Fujita
Naoki
N
Iwasa
Motoh
M
Kobayashi
Yoshinao
Y
Gabazza
Esteban Cesar
EC
Adachi
Yukihiko
Y
Konishi
Masayoshi
M
Watanabe
Shozo
S
D000410:Alanine Transaminase / Q000097:blood*; D001782:Blood Donors; D029407:GB virus C / Q000235:genetics / Q000302:isolation & purification / Q000648:ultrastructure*; D006525:Hepatitis, Viral, Human / Q000097:blood / Q000821:virology*; D006801:Humans; D046529:Microscopy, Electron, Transmission
D000410:Alanine Transaminase