Laboratory and Epidemiology Communications

GB Virus C/Hepatitis G Virus Does Not Induce Expression of
p44 Antigen in Chimpanzee Hepatocytes
Yohko K. Shimizu*, Minako Hijikata and Hiroshi Yoshikural
Department ofRespiratoyy Diseases, Research Institute, International Medical Center ofJapan,
Toyama 1‑21‑1 Shinjuku‑ku, Too,0 162‑8655 andJNational Institute ofInfectious Diseases,
Toyama 1‑23‑1, Shinjuku‑ku, Tokyo 162‑8640
Communicated by Hiroshi Ybshikura(Accepted June 1, 2001)

The cytoplasmic antlgen, p44, was orlglnally discovered

found chimpanzees whose sera were positive for GBV‑C什IGV

in hepatocytes of chimpanzees experimentally infected withRNA by RTIPCR. Utilizing the liver biopsy specimens collected

the parenterally transmitted fbm of non‑A, non‑B hepatitis
virus (NANBHV) (1). Expression of the antigen, found infrom these chimpanzees, We investlgated appearance of thep44 antigen and the related tubular stmctures in hepatocytes･
The inoculum used for the transmission study was obtained

parallel with unique ultrastmctural alterations (2), appeared

to be a host‑response to infection with NANBHV or hepatitis

from an implicated donor. A 61‑year‑old woman received

delta virus, but not to infection with hepatitis A virus, hepatitis

thrombocytes &om her son, a healthy individual negative for

良 vims, or enterically transmitted NANBHV Until hepatitis

hepatitis B surface antigen (HBsAg) and antibody to hepatitis

C vims (HCV) was molecularly cloned in 1989, showing thatmost parenterally transmitted NANBHV infections, p44 wasuseful as a reliable marker for the NANBHV (now HCV)B surface antigen (anti‑HBs), in the course of a splenectomyin 1981. She developed acute NANB hepatitis; her level ofserum transaminase (ALT) rose I 0 days after transfusion andinfection. The gene encoding p44 was subsequently isolated

peaked at 15 days. Semm was agaln COllected丘om the donor

and shown to be a member of the family of interferon‑a/a

3 months aRer donation, and 1 ml of 10‑2, 10 叫, and 1 O'6 dilution

inducible genes (3). lt is now speculated that p44 is possibly

was inoculated into chimpanzee #1310, #429, and #125,

one of the mediators involved in the antiviral action of inter‑respectively. All of the chimpanzees developed hepatitis asferon.

evidenced by the elevated level of serum ALT; the peak wasRecently, GB virus C (also called as hepatitis G virus)

at week 2 for #1310, at week 12 for#429, and at week 5 for#125.

(GBV‑C/HGV), which is closely related to but distinct from

HCV was discovered. Although they share little sequence

Serum samples and liver biopsy specimens collected athomology, HCV and GBVIC/HGV have a qulte Similar genetic

intervals from chimpanzees #429 and #125 Were availableorganization, With the exceptlOn that the latter almost lacks

for the present assays. For both chimpanzees, all of the serum

sequences encoding a core protein. We were interested to know
if GBV‑C/HGV induces p44, as both vimses presumably

samples were negative for HCV RNA as measured by RT‑
PCR, as well as anti‑CIOO HCV antibody as measured byreplicate via double‑stranded RNA replicative intermediate,

ELISA, throughout the obseⅣation period of 3 5 weeks. GBV‑

an interferon inducer.

When we retrospectively examined samples from theC/HGV RNA, as detected by RT‑PCR with primers detectlng
the 5 'non‑coding region Ofthe viral genome, became transiently

NANBHV transmission studies conducted in the 1980S, wepositive atト2 Weeks and then continuously positive at 10‑

35 weeks in chimpanzee #429 (Fig. lA). In chimpanzee #125,*Corresponding author: E‑mail: yshimizu@ri.imcj.go.jp

GBV･C什IGV RNA was detected at 3‑8 weeks, then reappeared89Jpn. J･ Infect･ Dis･, 54, 2001

Areek 12)･ These observations, together with the ALT eleva‑tlOn in infected chimpanzees, indicated actual viral replica‑

Chimp429

tion in the liver.

HepatlCP44A9 ‑SeTUmHGVRNA∞lL +l I l

Tubu一ar Structuro ‑Il +Il +Desplte its similarlty tO HCV GBV‑C/HGV was unable toー l‑‑++l++induce neither p44 nor tubular stmctures which are constantly++++++

induced by HCV. Because the gene encoding p44 is interferon‑inducible, the production ofp44 alter HCV infection has been

50(zuJJm)ト1V

explained by the production of interferon which is inducedby double‑stranded RNA replicative intemediates. However,
GBV‑C/HGV's failure to induce p44 apparently does not fit
this hypothesis, since GBV‑C/HGV in the same family also is

expected to replicate via a double‑stranded RNA intemediate･
0510

1520

253035

These considerations lead us to speculate that the double‑

Weeks postinoculatjon

stranded RNA intermediates may not be the major inducer ofB

p44 even in HCV The question then remains as the identltyof the inducer? The major difference in the genetic constitu‑

Chimp125

tion of the two viruses is the near deletion ofa core protein in

Tubu一ar Structure ‑Hepatic p44A9‑

SerumHGVRNA‑一一++

GBV‑C/HGV The possibility of the role ofa core protein in
十一一+++++十p44 induction remains to be tested.

亨50

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Arocena, C.,Angeles, M.and Carreno, V. (2000): Exsistencecomparlng the 5'non‑Co°ing sequences in the serum and inof distinct GB virus‑C/Hepatitis G virus variants withdifferent tropISm. J. Viro1., 74, 7936‑7942.

the liver of chimpanzee #429 Obtained on the same day (at90