Long-Term Persistent GBV-B Infection and Development of a Chronic and Progressive Hepatitis C-Like Disease in Marmosets

狨猴长期持续感染GBV-B病毒并发展为慢性进行性丙型肝炎样疾病

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作者:Yuki Iwasaki,Ken-Ichi Mori, Koji Ishii, Noboru Maki, Sayuki Iijima, Tomoyuki Yoshida, Sachi Okabayashi, Yuko Katakai, Young-Jung Lee, Akatsuki Saito, Hiromi Fukai, Nobuyuki Kimura, Naohide Ageyama, Sayaka Yoshizaki, Tetsuro Suzuki, Yasuhiro Yasutomi, Tatsuo Miyamura, Mari Kannagi, Hirofumi Akari

Abstract

It has been shown that infection of GB virus B (GBV-B), which is closely related to hepatitis C virus, develops acute self-resolving hepatitis in tamarins. In this study we sought to examine longitudinally the dynamics of viral and immunological status following GBV-B infection of marmosets and tamarins. Surprisingly, two of four marmosets but not tamarins experimentally challenged with GBV-B developed long-term chronic infection with fluctuated viremia, recurrent increase of alanine aminotransferase and plateaued titers of the antiviral antibodies, which was comparable to chronic hepatitis C in humans. Moreover, one of the chronically infected marmosets developed an acute exacerbation of chronic hepatitis as revealed by biochemical, histological, and immunopathological analyses. Of note, periodical analyses of the viral genomes in these marmosets indicated frequent and selective non-synonymous mutations, suggesting efficient evasion of the virus from antiviral immune pressure. These results demonstrated for the first time that GBV-B could induce chronic hepatitis C-like disease in marmosets and that the outcome of the viral infection and disease progression may depend on the differences between species and individuals.

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