HCV in peripheral blood mononuclear cells are predominantly carried on the surface of cells in HIV/HCV co-infected individuals.
HCV replication in extra-hepatic reservoirs has been suggested to occur in many tissues including PBMCs. A recent study showed evidence for compartmentalization and evolution of HCV in PBMCs. However, the cells that support HCV replication in PBMCs have not been identified. In this study we have fractionated the PBMC from HIV/HCV co-infected patients into T, monocytes, B and NK cells, and most of the HCV was located in CD3-cell fractions. Protease treatment of PBMCs to remove cell surface receptors resulted in the loss of HCV RNA suggesting that most of the HCV is present on the cell surface. PBMCs were treated by freeze-thaw nuclease method that would protect the HCV RNA in the virus but not the intracellular viral RNA. Data from this analysis support the conclusion that most of HCV is present on the cell surface. Even though the presence of minus strand RNA in PBMCs suggests that a low level HCV replication takes place within the PBMCs of HIV/HCV co-infected individuals, HCV in PBMC is present mainly on the surface of non-T cells, mostly on NK, monocytes and B cells. These results suggest a unique pathogenic role of NK, monocyte and B cells as carriers of HCV.
Natarajan
Ven
V
Laboratory of Molecular Cell Biology, SAIC-Frederick, Inc., Frederick, Maryland, USA.
Kottilil
Shyam
S
Hazen
Allison
A
Adelsberger
Joseph
J
Murphy
Alison A
AA
Polis
Michael A
MA
Kovacs
Joseph A
JA
D000328:Adult; D001402:B-Lymphocytes / Q000821:virology; D004197:Disease Reservoirs; D005434:Flow Cytometry; D015658:HIV Infections / Q000150:complications* / Q000821:virology; D016174:Hepacivirus / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism; D006526:Hepatitis C / Q000150:complications* / Q000821:virology; D006801:Humans; D007694:Killer Cells, Natural / Q000821:virology; D007963:Leukocytes, Mononuclear / Q000821:virology*; D008875:Middle Aged; D009000:Monocytes / Q000821:virology; D011956:Receptors, Cell Surface / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014779:Virus Replication
D011956:Receptors, Cell Surface