PMID- 15185313
OWN - NLM
STAT- MEDLINE
DCOM- 20040830
LR  - 20240109
IS  - 0270-9139 (Print)
IS  - 0270-9139 (Linking)
VI  - 39
IP  - 6
DP  - 2004 Jun
TI  - Hepatitis C virus kinetics and host responses associated with disease and outcome 
      of infection in chimpanzees.
PG  - 1709-20
AB  - 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.
FAU - Major, Marian E
AU  - Major ME
AD  - Laboratory of Hepatitis Viruses, Division of Viral Products/Center for Biologics 
      Evaluation and Research /Food and Drug Administration, Bethesda, MD, USA. 
      major@cber.fda.gov
FAU - Dahari, Harel
AU  - Dahari H
FAU - Mihalik, Kathleen
AU  - Mihalik K
FAU - Puig, Montserrat
AU  - Puig M
FAU - Rice, Charles M
AU  - Rice CM
FAU - Neumann, Avidan U
AU  - Neumann AU
FAU - Feinstone, Stephen M
AU  - Feinstone SM
LA  - eng
GR  - CA85883/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Hepatology
JT  - Hepatology (Baltimore, Md.)
JID - 8302946
RN  - 0 (Cytokines)
RN  - 0 (Hepatitis C Antibodies)
SB  - IM
CIN - Hepatology. 2005 Mar;41(3):679. PMID: 15723317
MH  - Animals
MH  - Ape Diseases/*virology
MH  - Cytokines/biosynthesis
MH  - Female
MH  - Hepacivirus/*physiology
MH  - Hepatitis C/immunology/metabolism/*veterinary/virology
MH  - Hepatitis C Antibodies/biosynthesis
MH  - Kinetics
MH  - Male
MH  - *Pan troglodytes
MH  - Time Factors
EDAT- 2004/06/09 05:00
MHDA- 2004/08/31 05:00
CRDT- 2004/06/09 05:00
PHST- 2004/06/09 05:00 [pubmed]
PHST- 2004/08/31 05:00 [medline]
PHST- 2004/06/09 05:00 [entrez]
AID - 10.1002/hep.20239 [doi]
PST - ppublish
SO  - Hepatology. 2004 Jun;39(6):1709-20. doi: 10.1002/hep.20239.