Evidences of Apoptosis in Hepatitis C Virus-Infected Hepatocytes and Peripheral Blood Monocuclear Cells in the Absence of Liver Injury
Viviana Falcón, Nelson Acosta-Rivero, Mineko Shibayama, Jose Luna-Munoz, Magdalena Miranda-Sanchez, María-C de la Rosa, Ivón Menéndez, Waldo García, Bienvenido Gra, Santiago Dueñas-Carrera, Deliana Lopez, Maritza González Bravo, Celia Fernández-Ortega, Dionne Casillas, Juan Morales, Juan Kouri and Victor Tsutsumi
DOI : 10.3844/ajidsp.2005.43.49
American Journal of Infectious Diseases
Volume 1, Issue 1
Understanding the mechanism of Hepatitis C Virus (HCV) pathogenesis is an important part of HCV research. In this study, the presence of apoptosis in HCV-infected liver and Peripheral Blood Mononuclear Cells (PBMC) from patients positive for anti-HCV antibodies and negative for serum HCV-RNA was investigated. The samples obtained from 21 patients were studied by in situ Hybridization (ISH), Immunofluorescence, TUNEL reaction and caspase 3 activation assays. The findings show that both DNA fragmentation by TUNEL assay and activation of caspase 3 were detected in hepatocytes from patients histologically confirmed as bearing chronic hepatitis or with abnormal ALAT or GGTP as well as in patients with no histological evidences of chronic hepatitis and normalization of transaminases. Apoptotic cells were also detected in PBMC samples by the TUNEL assay. ISH analysis of liver biopsies and PBMC samples showed both positive and negative strands of the HCV genome localized in some cells showing nuclear characteristics of apoptosis such as chromatin margination, condensation and fragmentation. These typical morphological changes of apoptotic cell death were also observed in some hepatocytes showing reaction products suggestive of HCcAg. Data suggest that under certain conditions HCV induces apoptosis in the absence of liver injury. Induction of apoptosis in HCV-infected cells may interfere with viral replication, which may lead to undetectable levels of HCV-RNA in serum.
© 2005 Viviana Falcón, Nelson Acosta-Rivero, Mineko Shibayama, Jose Luna-Munoz, Magdalena Miranda-Sanchez, María-C de la Rosa, Ivón Menéndez, Waldo García, Bienvenido Gra, Santiago Dueñas-Carrera, 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.