Evidences of Hepatitis C Virus Replication in Hepatocytes and Peripheral Blood Monocuclear Cells from Patients Negative for Viral RNA in Serum
Viviana Falcón, Nelson Acosta-Rivero, Mineko Shibayama, Jose Luna-Munoz, Magdalena Miranda-Sanchez, María-C de la Rosa, Ivón Menéndez, Bienvenido Gra, Santiago Dueñas-Carrera, Waldo García, Eduardo Vilar, Jose Silva, Deliana Lopez, Maritza González-Bravo, Celia Fernández-Ortega, Dionne Casillas, Juan Morales, Juan Kouri and Victor Tsutsumi
DOI : 10.3844/ajidsp.2005.34.42
American Journal of Infectious Diseases
Volume 1, Issue 1
In this study, we examined the expression of hepatitis C virus (HCV) components in hepatocytes and peripheral blood mononuclear cells (PBMC) from patients positive for anti-HCV antibodies and negative for serum HCV-RNA. The samples obtained from 25 randomly selected patients (13 of 25 patients showed no histological evidences of chronic hepatitis and had normal serum ALAT and GGTP levels) were studied by in situ Hybridization and Immunofluorescence assays. The findings show that HCV-RNA of both positive and negative polarity was carried in the hepatocytes of more than 80% of cases. The proportion of cells expressing the negative strand (mean ± SD, 10.25% ± 5.56%) was lower than those expressing positive strand (mean ± SD, 19.88% ± 9.19%) (p=0.0076; Student’s t test). In addition, reaction products suggestive of HCV core, E1 and E2 antigens within hepatocytes were also observed. Both hybridization and immunofluorescence signals were localized in the cytoplasm suggesting that this is the place of active HCV replication. On the other hand, the HCV-RNA of positive polarity was detected in PBMC from 16 out of 17 samples analyzed (94%) while the HCV-RNA of negative polarity was detected in 82% of samples investigated. Positive hybridization signals were localized in the cytoplasm of PBMC. Interestingly, 12 out of 13 patients with clinical and histological resolution of hepatitis, contain HCV-RNA in either liver or PBMC. These results provide further evidences that the intermediate replicative form of the HCV genome can persist in hepatocytes and PBMC after apparently complete resolution of chronic hepatitis C.
© 2005 Viviana Falcón, Nelson Acosta-Rivero, Mineko Shibayama, Jose Luna-Munoz, Magdalena Miranda-Sanchez, María-C de la Rosa, Ivón Menéndez, Bienvenido Gra, Santiago Dueñas-Carrera, Waldo García, Eduardo Vilar, Jose Silva, Deliana Lopez, Maritza González-Bravo, Celia Fernández-Ortega, Dionne Casillas, Juan Morales, Juan Kouri and Victor Tsutsumi. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.