PMID- 19297478
OWN - NLM
STAT- MEDLINE
DCOM- 20090529
LR  - 20211020
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 83
IP  - 11
DP  - 2009 Jun
TI  - Differential effects of hepatitis C virus JFH1 on human myeloid and plasmacytoid 
      dendritic cells.
PG  - 5693-707
LID - 10.1128/JVI.02671-08 [doi]
AB  - Dendritic cells (DCs) are reported to be functionally deficient during chronic 
      hepatitis C virus (HCV) infection. Differing results have been reported on direct 
      effects of intact replicative-form HCV on DC function. To better understand the 
      effect of HCV on DC function, we treated freshly purified human myeloid DCs 
      (mDCs) and plasmacytoid DCs (pDCs) with HCV JFH1. We found that HCV upregulated 
      mDC maturation marker (CD83, CD86, and CD40) expression and did not inhibit 
      Toll-like receptor 3 (TLR3) ligand [poly(I:C)]-induced mDC maturation, a finding 
      consistent with the phenotype of DCs from HCV-infected subjects. At the same 
      time, HCV JFH1 inhibited the ability of poly(I:C)-treated mDCs to activate naive 
      CD4 T cells. In contrast, although there was no direct effect of virus on pDC 
      maturation, HCV JFH1 inhibited TLR7 ligand (R848)-induced pDC CD40 expression, 
      and this was associated with impaired ability to activate naive CD4 T cells. 
      Parallel experiments with recombinant HCV proteins indicated HCV core protein may 
      be responsible for a portion of the activity. Furthermore, HCV-mediated mDC 
      maturation was dependent upon CD81-E2 interaction and, in part, TLR2. Using 
      UV-treated HCV, we show that HCV-mediated mDC and pDC maturation is virus 
      replication independent and, using strand specific PCR, we found no evidence for 
      HCV replication within DCs. Because these effects of HCV on DC subset maturation 
      and function in part recapitulate direct ex vivo analysis of DCs in chronic HCV 
      infection, the mechanisms described here likely account for a portion of the DC 
      subset defects observed in vivo.
FAU - Liang, Hua
AU  - Liang H
AD  - Department of Medicine, Division of Infectious and Rheumatic Diseases, Case 
      Western Reserve University, Center for AIDS Research and VA Medical Center, 
      Cleveland Ohio 44106, USA.
FAU - Russell, Rodney S
AU  - Russell RS
FAU - Yonkers, Nicole L
AU  - Yonkers NL
FAU - McDonald, David
AU  - McDonald D
FAU - Rodriguez, Benigno
AU  - Rodriguez B
FAU - Harding, Clifford V
AU  - Harding CV
FAU - Anthony, Donald D
AU  - Anthony DD
LA  - eng
GR  - R01 DK068361/DK/NIDDK NIH HHS/United States
GR  - IF31AA017853/AA/NIAAA NIH HHS/United States
GR  - P30 AI036219/AI/NIAID NIH HHS/United States
GR  - F31 AA017853/AA/NIAAA NIH HHS/United States
GR  - AI 36219/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20090318
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (Antigens, CD)
RN  - 0 (Ligands)
RN  - 0 (Toll-Like Receptors)
SB  - IM
MH  - Antigens, CD/immunology
MH  - CD4-Positive T-Lymphocytes/immunology
MH  - Cell Differentiation/immunology
MH  - Cells, Cultured
MH  - Dendritic Cells/cytology/*immunology/metabolism
MH  - Hepacivirus/*physiology
MH  - Humans
MH  - Immunity, Innate/immunology
MH  - Ligands
MH  - Lymphocyte Activation/immunology
MH  - Myeloid Cells/cytology/*immunology/metabolism
MH  - Toll-Like Receptors/immunology/metabolism
MH  - Virus Replication
PMC - PMC2681964
EDAT- 2009/03/20 09:00
MHDA- 2009/05/30 09:00
PMCR- 2009/12/01
CRDT- 2009/03/20 09:00
PHST- 2009/03/20 09:00 [entrez]
PHST- 2009/03/20 09:00 [pubmed]
PHST- 2009/05/30 09:00 [medline]
PHST- 2009/12/01 00:00 [pmc-release]
AID - JVI.02671-08 [pii]
AID - 2671-08 [pii]
AID - 10.1128/JVI.02671-08 [doi]
PST - ppublish
SO  - J Virol. 2009 Jun;83(11):5693-707. doi: 10.1128/JVI.02671-08. Epub 2009 Mar 18.