The issue of infection of peripheral blood mononuclear cells (PBMC) by
the hepatitis C virus (HCV) has potentially important implications, b
ut is still debated. We have used the severe combined immunodeficiency
(SCID) mouse model to test for the persistence of HCV in PBMC, Hemato
poietic cells isolated from 14 subjects infected by HCV were inoculate
d intraperitoneally into SCID mice. Serum and blood cell samples from
these mice were obtained with a mean follow-up of 8 weeks. As controls
, human fibroblasts and sheep PBMC, preincubated with a human HCV-posi
tive serum, were inoculated concomitantly into mice and analyzed. HCV-
RNA positive strands were detected in 7 of 26 serum samples and 8 of 2
6 cell fractions from SCID mice inoculated with HCV-positive PBMC, aft
er 8 weeks of follow-up. In contrast, no HCV RNA was detectable in the
10 control mice. HCV-RNA negative strands were detected in only 2 of
10 tested samples from 2 mice, and both positive mice had been inocula
ted with PBMC from HCV-positive subjects with malignant hematopoietic
syndrome. Our study offers strong evidence for the persistence of HCV
infection in mononuclear cells. Our results are also consistent with a
low rate of HCV multiplication. This SCID mouse model might therefore
be useful in analyzing the mechanisms of HCV persistence in mononucle
ar cells.