Internal ribosomal entry-site activities of clinical isolate-derived hepatitis A virus and inhibitory effects of amantadine.
OBJECTIVE
Little is known about specific naturally-occurring internal ribosomal entry site (IRES) activities of hepatitis A virus (HAV). We examined these activities using the bicistronic reporter assay and the effects of antiviral amantadine against their activities.


METHODS
Six HAV IRES clones from three patients with fulminant hepatitis and three with self-limited acute hepatitis were obtained. The activities of their IRES were analyzed using bicistronic reporter assay in hepatocyte- and non-hepatocyte-derived cell lines, and the potential efficaciousness of the amantadine was examined.


RESULTS
One clone from fulminant hepatitis had a deletion in domains III-IV of HAV IRES had higher IRES activities than HM175 in HLE and Huh-7 cells. In Huh-7 cells, amantadine is effective for inhibiting HAV IRES activities, and especially fulminant hepatitis-derived ones.


CONCLUSIONS
HAV IRES derived from clinical isolates have various activities. Bicistronic reporter assay using clinical isolates may be another useful tool for testing antiviral activities like those of amantadine and the new acridines and hydrazones recently reported.
Kanda
Tatsuo
T
Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Imazeki
Fumio
F
Nakamoto
Shingo
S
Okitsu
Kohichiroh
K
Fujiwara
Keiichi
K
Yokosuka
Osamu
O