• Decrease font size
  • Return font size to normal
  • Increase font size
U.S. Department of Health and Human Services

Scientific Publications by FDA Staff

  • Print
  • Share
  • E-mail

Search Publications



Starting Date

Ending Date

Order by

Entry Details

Hepatology 2004 Jun;39(6):1709-20

Hepatitis C virus kinetics and host responses associated with disease and outcome of infection in chimpanzees.

Major ME, Dahari H, Mihalik K, Puig M, Rice CM, Neumann AU, Feinstone SM

Major ME, US FDA, DVP, CBER, Lab Hepatitis Viruses, Bldg 29A,Rm 1D10,HFM448,8800 Rockville Pike, Bethesda, MD 20892 USA US FDA, DVP, CBER, Lab Hepatitis Viruses, Bethesda, MD 20892 USA Bar Ilan Univ, Fac Life Sci, Ramat Gan, Israel Rockefeller Univ, Ctr Study Hepatitis C, New York, NY 10021 USA


To study determinants of clinical outcome following HCV infection, viral kinetics, immune events, and intrahepatic cytokine markers were compared in 10 naive chimpanzees. Four of the animals cleared HCV; 6 developed persistent infections. All animals developed similar acute infections with increasing viremia from 1 to 2 weeks, followed by alanine aminotransferase (ALT) elevations and seroconversion. This viremia pattern consisted of a biphasic increase, a rapid slope (mean doubling time [t(2)] = 0.5 days) followed by a slower slope after the second week (t(2) = 7.5 days). This slowing of virus replication correlated in all animals with increased intrahepatic 2'5' oligoadenylate synthetase 1 (2OAS-1) messenger RNA (mRNA) levels and was independent of disease outcome. An effective control of virus replication was observed following increases in intrahepatic interferon gamma (IFN-gamma) mRNA and ALT levels. Although this control was associated in all animals with a 2-log decrease in virus titer, the timing occurred approximately 2 weeks later in the chronic group (P <.05). Additionally, while cleared infections were characterized by a continual decrease in virus titer, the titers in the persistent infections reached a steady state level of 10(4) to 10(5) RNA copies/mL. This inability of the immune response to sustain viral clearance in the persistent infections was associated with a reduced intrahepatic CD3e and monocyte-induced protein 1alpha (MIP-1alpha) mRNA induction. In conclusion, these data indicate that, regardless of outcome, chimpanzees generate responses that control HCV replication during the early and late acute phase. However, the pathogenesis of HCV may be determined by a more rapid onset of the induced response and the cell population that migrates to the liver. (HEPATOLOGY 2004;39:1709-1720.)

Category: Journal Article, Peer
PubMed ID: #15185313
Includes FDA Authors from Scientific Area(s): Biologics
Entry Created: 2011-10-04 Entry Last Modified: 2012-08-29