HCV Hepatocytes Kill HIV Hepatocytes through TRAIL Figure 3. HCV core protein Increases TRAIL but not TRAIL-R2. (A and B) Huh7 cells were transfected with HCV core protein for increasing amounts of time and then analyzed for TRAIL expression by Flow cytometry or (D and E) Western blot. (C) Huh7.5 cells were infected with the JFH1 HCV genotype 2a and analyzed for TRAIL by Western blot. (F) Huh7 cells were treated with doxycycline for increasing amounts of time and analyzed for TRAIL by Western blot (G) Huh7 cells were treated with increasing concentrations of soluble HCV core protein or control and analyzed for TRAIL by Western blot (H) In parallel HCV core transfected Huh7 cells were analyzed for TRAIL-R2 expression by Western blot. doi:10.1371/journal.pone.0027171.g003 HIV RNA and p24 antigen have been isolated from liver samples, presumably from HIV infected immune cells, indicating that HIV proteins are in close proximity to hepatocytes during HIV infection [32,33]. These proteins also contribute to the depletion of CD4+ T cells through multiple mechanisms, including HIV gp120 mediated bystander killing of uninfected Figure 4. In vivo analysis of TRAIL, TRAIL-R2 and Apoptosis in Human Livers. Liver samples from 10 HIV infected, 10 HCV infected, 10 HIV/ HCV infected or 10 uninfected individuals were stained by Immunohistochemistry for TRAIL, TRAIL-R2 or cleaved PARP. The images were taken with an Olympus Microscope with the 20x objective (TRAIL, TRAIL-R2), and 40x objective (PARP). Representative samples are shown. doi:10.1371/journal.pone.0027171.g004 PLoS ONE | www.plosone.org 4 November 2011 | Volume 6 | Issue 11 | e27171