title: Titration of hepatitis C virus in chimpanzees for determining the copy number required for transmission.
abstract: OBJECTIVE
  To determine the copy number of hepatitis C virus (HCV) RNA, determined by nucleic acid amplification test (NAT) for screening blood units in Japan, that can transmit infection to chimpanzees.
  
  
  METHODS
  Fresh-frozen plasma with markers of HCV infection, as well as inocula pedigreed from 1 of them, were evaluated for the infectious activity in chimpanzees.
  
  
  RESULTS
  One unit each (273-282 ml) of fresh-frozen plasma from 2 blood donors or a pool from 13 donors to make a unit, which contained high-titered antibody to HCV but without HCV RNA detectable by NAT, did not infect any of 3 chimpanzees. Two chimpanzees were infected, however, when they were inoculated with 1 ml of serum from a blood donor in the 'window period' of HCV infection and containing 7.0 x 10(6) copies/ml of HCV RNA. The preacute phase serum from 1 of them harvested 7 weeks after the inoculation was titrated in 2 chimpanzees, and an inoculum containing approximately 2 x 10(1) copies of HCV RNA could transmit infection to both of them.
  
  
  CONCLUSIONS
  Approximately 20 copies of HCV can transmit infection to recipients, which needs to be taken into consideration in planning the screening of blood units for HCV RNA by NAT. Although the sensitivity of present NAT could be improved further, there would be a limit of it in detecting a low-level HCV RNA in the window period of donors with the infectious capacity in recipients.
authors.affiliation: Department of Infectious Disease and Control, Hiroshima University Graduate School of Biomedical Sciences, Kasumi, Hiroshima, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Katayama
authors.forename: Junko
authors.initials: J
authors.lastname: Kumagai
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Komiya
authors.forename: Masaaki
authors.initials: M
authors.lastname: Mizui
authors.forename: Hisao
authors.initials: H
authors.lastname: Yugi
authors.forename: Shinya
authors.initials: S
authors.lastname: Kishimoto
authors.forename: Retsuji
authors.initials: R
authors.lastname: Yamanaka
authors.forename: Shigeru
authors.initials: S
authors.lastname: Tamatsukuri
authors.forename: Tetsushi
authors.initials: T
authors.lastname: Tomoguri
authors.forename: Yuzo
authors.initials: Y
authors.lastname: Miyakawa
authors.forename: Junko
authors.initials: J
authors.lastname: Tanaka
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yoshizawa
mesh_terms: D000818:Animals; D005260:Female; D016174:Hepacivirus / Q000302:isolation & purification*; D006526:Hepatitis C / Q000635:transmission*; D018937:Hepatitis C Antibodies / Q000097:blood; D008297:Male; D021141:Nucleic Acid Amplification Techniques; D002679:Pan troglodytes / Q000821:virology*; D012367:RNA, Viral / Q000097:blood*
chemical_list: D018937:Hepatitis C Antibodies; D012367:RNA, Viral