Up-regulation of hepatitis C virus replication by human T cell leukemia virus type I-encoded Tax protein.
Co-infection of hepatitis C virus (HCV) with other blood-borne pathogens such as human T cell leukemia virus (HTLV) is common in highly endemic areas. Clinical evidence showing a correlation between HTLV-I co-infection and rapid progression of HCV-associated liver disease promoted us to investigate the effect of HTLV-I-encoded Tax protein on HCV replication. Reporter assay showed that HCV replicon-encoded luciferase expression was significantly augmented by co-transfection of the Tax-expressing plasmid. Further, HCV RNA replication in replicon cells was increased either by co-culture with cells stably expressing Tax protein (Huhtax) or by culture in the presence of Huhtax-conditioned medium, indicating that Tax could also modulate HCV replication of adjacent cells in a paracrine manner. Additionally, HCV replication in Huhtax exhibited a reduced responsiveness to interferon-alpha-induced antiviral activity. This study demonstrates the facilitation of HCV replication by Tax protein, which may partially account for severer clinical consequences of HCV-related disease in HCV/HTLV co-infected individuals.
Zhang
Jing
J
Research and Development Center, FUSO Pharmaceutical Industries, LTD., 2-3-30 Morinomiya, Joto-ku, Osaka 536-8523, Japan. j-zhang@fuso-pharm.co.jp
Yamada
Osamu
O
Kawagishi
Kenji
K
Yoshida
Hiroshi
H
Araki
Hiromasa
H
Yamaoka
Shoji
S
Hattori
Toshio
T
Shimotohno
Kunitada
K
D000998:Antiviral Agents / Q000494:pharmacology; D002460:Cell Line; D018920:Coculture Techniques / Q000379:methods; D017077:Culture Media, Conditioned / Q000737:chemistry; D016356:Gene Products, tax / Q000502:physiology*; D017930:Genes, Reporter; D016174:Hepacivirus / Q000254:growth & development* / Q000276:immunology; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology; D008156:Luciferases / Q000096:biosynthesis; D015854:Up-Regulation; D014779:Virus Replication / Q000502:physiology*
D000998:Antiviral Agents; D017077:Culture Media, Conditioned; D016356:Gene Products, tax; D016898:Interferon-alpha; C514970:tax protein, Human T-lymphotrophic virus 1; D008156:Luciferases