GB Virus C/Hepatitis G Virus Does Not Induce Expression of P44 Antigen in Chimpanzee Hepatocytes Yohko K

Jpn. J. Infect. Dis., 54, 2001 and skin were removed was purchased on the previous night ongln Of infection was not clear. The food service in a festival of the festival. It was left in the room temperature ovemight. as described in the present case does not requlre regulation The cooking started at 4 0'clock in the momlng by roastlng under the food hyglene law. This incident indicated the the bulk meat by rotation over a gas bumer. The meat was necessity of proper measures for food security in this type of covered by a large steel box during roastlng. It was cut into short temporary food service and regulatory measures in case small pleCeS and served at 10 o'clock in the momlng. Some of possible occurrences of food poISOnlng. noted that some portion of the meat was rare; i.e., it was insufficiently cooked. Laboratory and other epidemiologlCal data will be published ln the outbreak, a total 58 cases were counted. There were in Infectious Agents Surveillance Report, vol. 22 (June, 200 I ). 41 primary infections, 1 1 secondary infections including a We thank the clinical institutions, schools and other institu- case which took place in a nursery school, and 6 cases whose tions fわr their collaboration. 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 and JNational 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 with RNA by RTIPCR. Utilizing the liver biopsy specimens collected the parenterally transmitted fbm of non-A, non-B hepatitis from these chimpanzees, We investlgated appearance of the virus (NANBHV) (1). Expression of the antigen, found in p44 antigen and the related tubular stmctures in hepatocytes･ parallel with unique ultrastmctural alterations (2), appeared The inoculum used for the transmission study was obtained 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 that B surface antigen (anti-HBs), in the course of a splenectomy most parenterally transmitted NANBHV infections, p44 was in 1981. She developed acute NANB hepatitis; her level of useful as a reliable marker for the NANBHV (now HCV) serum transaminase (ALT) rose I 0 days after transfusion and infection. 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 as feron. evidenced by the elevated level of serum ALT; the peak was Recently, GB virus C (also called as hepatitis G virus) at week 2 for #1310, at week 12 for#429, and at week 5 for (GBV-C/HGV), which is closely related to but distinct from #125. HCV was discovered. Although they share little sequence Serum samples and liver biopsy specimens collected at homology, HCV and GBVIC/HGV have a qulte Similar genetic intervals from chimpanzees #429 and #125 Were available organization, 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 samples were negative for HCV RNA as measured by RT- if GBV-C/HGV induces p44, as both vimses presumably PCR, as well as anti-CIOO HCV antibody as measured by replicate via double-stranded RNA replicative intermediate, ELISA, throughout the obseⅣation period of 3 5 weeks. GBV- an interferon inducer. C/HGV RNA, as detected by RT-PCR with primers detectlng When we retrospectively examined samples from the the 5 'non-coding region Ofthe viral genome, became transiently NANBHV transmission studies conducted in the 1980S, we positive atト2 Weeks and then continuously positive at 10- 35 weeks in chimpanzee #429 (Fig. lA). In chimpanzee #125, *Corresponding author: E-mail: [email protected] GBV･C什IGV RNA was detected at 3-8 weeks, then reappeared 89 Jpn. J･ Infect･ Dis･, 54, 2001 A reek 12)･ These observations, together with the ALT eleva- tlOn in infected chimpanzees, indicated actual viral replica- Chimp429 tion in the liver. Tubu一ar Structuro - l I l l L + I l + I l + ー l Desplte its similarlty tO HCV GBV-C/HGV was unable to HepatlCP44A9 - - induce neither p44 nor tubular stmctures which are constantly SeTUmHGVRNA -++ l + + + ++ ++ + induced by HCV. Because the gene encoding p44 is interferon- ∞ 50 (zuJJm)ト1V inducible, the production ofp44 alter HCV infection has been explained by the production of interferon which is induced by 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･ 0 5 10 15 20 25 30 35 Weeks postinoculatjon These considerations lead us to speculate that the double- stranded RNA intermediates may not be the major inducer of B p44 even in HCV The question then remains as the identlty Chimp125 of the inducer? The major difference in the genetic constitu- Tubu一ar Structure - tion of the two viruses is the near deletion ofa core protein in Hepatic p44A9 - GBV-C/HGV The possibility of the role ofa core protein in SerumHGVRNA -一一++ 十一一 + + + + + 十 p44 induction remains to be tested. 亨50 ii::ヨ REFERENCES =) ト _｣ I. Shimizu, Y. 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(1994): Induction of the human gene for p44, a hepatitis antibody (4) and for the cytoplasmic tubular structures in the C associated microtubular aggregate protein, by interferon- hepatocytes by electron microscopy. Neither was detected α/β. Eur. ∫. Biochem., 224, 877-883. (Figs. lA and lB). 4. Maeda, T., Honda,Y., Hanawa, M., Yamada, E., Ono,Y., It remains unclear whether the liver is the main target for Shikata, T. and Shimizu, Y K. (1989): Production of GBV-C/HGV replication. Fogeda et al. (5) analyzed viral antibodies directed agalnSt microtubular aggregates in sequences recovered from sera, livers, and peripheral blood hepatocytes of chimpanzees with non-A, non-B hepatitis. mononuclear cells from chronically infected patients and J. Gen.Viro1., 70, 140ト1407. demonstrated the existence of different GBV-C/HGV variants 5. Fogeda, M., Lopez-AIcorocho, ∫. M., Bartolome, ∫., with different tissue tropISm. We obtained similar data by Arocena, C.,Angeles, M.and Carreno, V. (2000): Exsistence comparlng the 5'non-Co°ing sequences in the serum and in of distinct GB virus-C/Hepatitis G virus variants with the liver of chimpanzee #429 Obtained on the same day (at different tropISm. J. Viro1., 74, 7936-7942. 90.

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