Hepatitis C virus replicates in the same immune cell subsets in chronic hepatitis C and occult infection.
OBJECTIVE
Infection of the lymphatic system by hepatitis C virus (HCV) appears to be an intrinsic characteristic of chronic hepatitis C (CHC) and low-level (occult) HCV infection, but the subsets of immune cells involved were not defined. The aim of this study was to characterize HCV replication status and to assess virus compartmentalization in CD4+ and CD8+ T lymphocytes, B cells, and monocytes in CHC, and silent infection persisting after resolution of hepatitis C.


METHODS
Immune cell subtypes isolated from 7 patients with CHC and 7 individuals with occult infection were analyzed for HCV-RNA-positive and -negative strands and, in selected cases, nonstructural protein 5A display and HCV variants.


RESULTS
All subtypes of immune cells investigated support HCV replication in both forms of infection, although significant differences were found between patients, and virus loads in the cells were greater in CHC than in occult infection. Although HCV RNA occurred at a comparable frequency in all cell subtypes in CHC, monocytes contained the greatest loads. In contrast, B cells tended to carry the highest virus quantities in occult infection, whereas monocytes appeared to be the least frequently infected. Detection of HCV nonstructural protein 5A and HCV variants that were not found in plasma confirmed virus replication in different immune cell types.


CONCLUSIONS
This work documents that the immune system supports HCV replication regardless of clinical appearance of infection and identifies immune cells that are reservoirs of HCV in symptomatic and occult infections.
Pham
Tram N Q
TN
Molecular Virology and Hepatology Research, Division of BioMedical Sciences, Memorial University, St. John,s, Newfoundland and Labrador, Canada.
King
Dawn
D
Macparland
Sonya A
SA
McGrath
Jerry S
JS
Reddy
S Bharati
SB
Bursey
Ford R
FR
Michalak
Tomasz I
TI
D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D001402:B-Lymphocytes / Q000821:virology*; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D018414:CD8-Positive T-Lymphocytes / Q000821:virology*; D002478:Cells, Cultured; D005260:Female; D005500:Follow-Up Studies; D016174:Hepacivirus / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism; D006526:Hepatitis C / Q000097:blood / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000097:blood / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009000:Monocytes / Q000821:virology*; D009154:Mutation; D012367:RNA, Viral / Q000097:blood; D013997:Time Factors; D019562:Viral Load; D017361:Viral Nonstructural Proteins / Q000097:blood; D014779:Virus Replication; D012324:RNA-Dependent RNA Polymerase
D000998:Antiviral Agents; D012367:RNA, Viral; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase