PMID- 24620791
OWN - NLM
STAT- MEDLINE
DCOM- 20150126
LR  - 20211021
IS  - 1365-2893 (Electronic)
IS  - 1352-0504 (Print)
IS  - 1352-0504 (Linking)
VI  - 21
IP  - 7
DP  - 2014 Jul
TI  - Infected hematopoietic stem cells and with integrated HBV DNA generate defective 
      T cells in chronic HBV infection patients.
PG  - e39-47
LID - 10.1111/jvh.12236 [doi]
AB  - A weak T-cell response plays a key role in the persistence of hepatitis B virus 
      (HBV) infection. We aimed to confirm that T-cell defects in patients with chronic 
      HBV infection are associated with HBV DNA infection of bone marrow (BM) 
      hematopoietic stem cells (HSCs). Using reverse transcription polymerase chain 
      reaction (RT-PCR) and fluorescence in situ hybridization (FISH), we observed the 
      transcription of HBsAg coding genes and confirmed the integration of HBV DNA in 
      CD34(+) BM HSCs from chronic HBV infection patients. T cells were generated by 
      coculturing the HSCs with delta-like ligand 1-expressing OP9 (OP9-DL1) cells. The 
      phenotypes of the T cells were then evaluated by flow cytometric (FACS) analysis 
      on days 14 and 25. The results demonstrated that fewer CD3(+) TCRabeta(+) CD3(+) 
      CD4(+) and CD4(+) CD8(+) T cells were generated from the HSCs of the patients 
      than from the healthy controls, (P < 0.01) but the frequency of CD3(+) D8(+) T 
      cells was not significantly different between the two group (P > 0.05). In 
      contrast, CD4(+) CD25(+) T cells were more in the patient group than in healthy 
      controls (P < 0.01) on both days 14 and 25. There were fewer CD3(+) CD4(+) 
      /CD3(+) CD8(+) cells in the patient group than in the healthy control group on 
      day 25 (P < 0.05). Less proliferation and lower levels of IL-2 and IFN- gamma were 
      also observed in the patient group compared with the control group (P < 
      0.05).These data suggest that HBV DNA infected and integrated into the BM HSCs 
      from patients with chronic HBV infection and that these BM HSCs generated 
      defective T cells.
CI  - (c) 2014 The Authors. Journal of Viral Hepatitis published by John Wiley & Sons 
      Ltd.
FAU - Shi, Y
AU  - Shi Y
AD  - Department of Infectious Disease, the First Affiliated Hospital of Harbin Medical 
      University, Harbin, China.
FAU - Lan, Y
AU  - Lan Y
FAU - Cao, F
AU  - Cao F
FAU - Teng, Y
AU  - Teng Y
FAU - Li, L
AU  - Li L
FAU - Wang, F
AU  - Wang F
FAU - Li, J
AU  - Li J
FAU - Zhou, J
AU  - Zhou J
FAU - Li, Y
AU  - Li Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140312
PL  - England
TA  - J Viral Hepat
JT  - Journal of viral hepatitis
JID - 9435672
RN  - 0 (Antigens, CD)
RN  - 0 (DNA, Viral)
RN  - 0 (Hepatitis B Surface Antigens)
SB  - IM
MH  - Antigens, CD/analysis
MH  - Cells, Cultured
MH  - Coculture Techniques
MH  - DNA, Viral/*isolation & purification
MH  - Flow Cytometry
MH  - Hematopoietic Stem Cells/*virology
MH  - Hepatitis B Surface Antigens/biosynthesis/genetics
MH  - Hepatitis C, Chronic/pathology/*virology
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Lymphocyte Subsets/chemistry/*immunology/*virology
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - T-Lymphocytes/chemistry/*immunology/*virology
PMC - PMC4237112
OTO - NOTNLM
OT  - HBV DNA
OT  - HSCs
OT  - T-cell defects
OT  - integration
OT  - replication
EDAT- 2014/03/14 06:00
MHDA- 2015/01/27 06:00
PMCR- 2014/11/19
CRDT- 2014/03/14 06:00
PHST- 2013/06/13 00:00 [received]
PHST- 2013/12/12 00:00 [accepted]
PHST- 2014/03/14 06:00 [entrez]
PHST- 2014/03/14 06:00 [pubmed]
PHST- 2015/01/27 06:00 [medline]
PHST- 2014/11/19 00:00 [pmc-release]
AID - 10.1111/jvh.12236 [doi]
PST - ppublish
SO  - J Viral Hepat. 2014 Jul;21(7):e39-47. doi: 10.1111/jvh.12236. Epub 2014 Mar 12.