title: Infectivity in chimpanzees (Pan troglodytes) of plasma collected before HCV RNA detectability by FDA-licensed assays: implications for transfusion safety and HCV infection outcomes.
abstract: Serial plasma aliquots (50 mL) obtained from 10 commercial donors who converted from hepatitis C virus (HCV) RNA negative to positive were transfused into 2 chimpanzees to assess infectivity during early HCV infection. Plasma, obtained 4 days before HCV RNA detectability by licensed assays, transmitted HCV infection to chimpanzee X355. The infectious PCR-negative plasma was subsequently shown to be positive in 2 of 23 replicates using a sensitive transcription-mediated amplification (TMA) assay, and estimated to contain 1.2 HCV RNA copies/mL (60 copies/50 mL transfused). Plasma units obtained up to 8 weeks earlier were not infectious in a second susceptible chimp, even when from donors with low-level, intermittent HCV RNA detection. Chimp x355 developed acute viremia with subsequent seroconversion, but cleared both virus and Ab in 17 weeks. When rechallenged 38 months later with 6000 RNA copies/mL from the same donor, X355 was transiently reinfected and again rapidly lost all HCV markers. We conclude that: (1) transfusions can transmit HCV infection before RNA detection, but the interval of test-negative infectivity is very brief; (2) early "blips" of HCV RNA appear noninfectious and can be ignored when calculating residual transfusion risk; and (3) markers of HCV infection can be lost rapidly after exposure to low-dose inocula.
authors.affiliation: Blood Systems Research Institute, San Francisco, CA 94118, USA. mbusch@bloodsystems.org
authors.forename: Michael P
authors.initials: MP
authors.lastname: Busch
authors.forename: Krishna K
authors.initials: KK
authors.lastname: Murthy
authors.forename: Steven H
authors.initials: SH
authors.lastname: Kleinman
authors.forename: Dale F
authors.initials: DF
authors.lastname: Hirschkorn
authors.forename: Belinda L
authors.initials: BL
authors.lastname: Herring
authors.forename: Eric L
authors.initials: EL
authors.lastname: Delwart
authors.forename: Vito
authors.initials: V
authors.lastname: Racanelli
authors.forename: Joo Chun
authors.initials: JC
authors.lastname: Yoon
authors.forename: Barbara
authors.initials: B
authors.lastname: Rehermann
authors.forename: Harvey J
authors.initials: HJ
authors.lastname: Alter
mesh_terms: D000818:Animals; D001782:Blood Donors / Q000331:legislation & jurisprudence; D058731:Blood Safety / Q000379:methods* / Q000592:standards; D001800:Blood Specimen Collection; D017848:Blood-Borne Pathogens / Q000302:isolation & purification; D005260:Female; D016174:Hepacivirus / Q000235:genetics* / Q000302:isolation & purification; D006526:Hepatitis C / Q000097:blood* / Q000175:diagnosis / Q000635:transmission* / Q000821:virology; D008004:Licensure; D057230:Limit of Detection; D002679:Pan troglodytes; D012367:RNA, Viral / Q000032:analysis / Q000097:blood* / Q000302:isolation & purification; D012698:Serologic Tests / Q000379:methods; D014481:United States; D014486:United States Food and Drug Administration / Q000331:legislation & jurisprudence
chemical_list: D012367:RNA, Viral