Changes in hepatitis C virus population in serum and peripheral blood mononuclear cells in chronically infected patients receiving liver graft from infected donors.
BACKGROUND
We have previously studied hepatitis C (HCV)-infected recipients of livers from HCV-infected donors and found that either the donor's strain or the recipient's strain predominate in serum. The current study was undertaken to determine whether these changes are complete and whether they are reflected in the population of virus associated with peripheral blood mononuclear cells (PBMCs).


METHODS
We analyzed HCV ribonucleic acid from sequential serum and PBMC samples from 11 and 8 patients, respectively. The relatively stable NS5 region was chosen for analysis because it allowed for dependable identification of donor and recipient strains. Viral sequences were analyzed by direct sequencing and by sensitive strain-specific polymerase chain reaction assays. These assays were capable of detecting the minor sequence present at a concentration 1:104-10-7 below that of the major sequence.


RESULTS
Five patients retained their original infecting strain; the donor strain was detected only transiently. In the remaining six patients, recipient strain was detected for the first few weeks, after which only the donor strain was consistently present. However, in one patient the second nondominant strain was detected from the background of the major strain on a single occasion 8 months after transplantation. All changes in serum were closely paralleled by those occurring in PBMCs.


CONCLUSIONS
Viral population changes in the setting of liver transplantation from HCV-infected donors to HCV-infected recipients occur simultaneously in PBMCs and serum. The takeover of one strain by another in PBMC- and serum-derived viral populations seemed to be complete and long lasting.
Radkowski
M
M
Department of Medicine, Mayo Clinic Scottsdale, 13400 East Shea Boulevard, Scottsdale, AZ 85259, USA.
Wang
L F
LF
Vargas
H
H
Wilkinson
J
J
Rakela
J
J
Laskus
T
T
D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D004279:DNA, Viral / Q000097:blood / Q000235:genetics; D016174:Hepacivirus / Q000235:genetics / Q000302:isolation & purification*; D019698:Hepatitis C, Chronic / Q000601:surgery* / Q000821:virology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology; D016031:Liver Transplantation; D008969:Molecular Sequence Data; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015163:Superinfection; D014019:Tissue Donors; D017361:Viral Nonstructural Proteins / Q000235:genetics; D014766:Viremia / Q000821:virology; D012324:RNA-Dependent RNA Polymerase
D017931:DNA Primers; D004279:DNA, Viral; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase