TY - JOUR
T1 - HIV-1 Nef is transferred from expressing T cells to hepatocytic cells through conduits and enhances HCV replication
AU - Park, In Woo
AU - Fan, Yan
AU - Luo, Xiaoyu
AU - Ryou, Myoung Gwi
AU - Liu, Jinfeng
AU - Green, Linden
AU - He, Johnny J.
PY - 2014/6/9
Y1 - 2014/6/9
N2 - HIV-1 infection enhances HCV replication and as a consequence accelerates HCV-mediated hepatocellular carcinoma (HCC). However, the precise molecular mechanism by which this takes place is currently unknown. Our data showed that infectious HIV-1 failed to replicate in human hepatocytic cell lines. No discernible virus replication was observed, even when the cell lines transfected with HIV-1 proviral DNA were co-cultured with Jurkat T cells, indicating that the problem of liver deterioration in the co-infected patient is not due to the replication of HIV-1 in the hepatocytes of the HCV infected host. Instead, HIV-1 Nef protein was transferred from nef-expressing T cells to hepatocytic cells through conduits, wherein up to 16% (average 10%) of the cells harbored the transferred Nef, when the hepatocytic cells were co-cultured with nefexpressing Jurkat cells for 24 h. Further, Nef altered the size and numbers of lipid droplets (LD), and consistently upregulated HCV replication by 1.5∼2.5 fold in the target subgenomic replicon cells, which is remarkable in relation to the initially indolent viral replication. Nef also dramatically augmented reactive oxygen species (ROS) production and enhanced ethanol-mediated up-regulation of HCV replication so as to accelerate HCC. Taken together, these data indicate that HIV-1 Nef is a critical element in accelerating progression of liver pathogenesis via enhancing HCV replication and coordinating modulation of key intra- and extra-cellular molecules for liver decay.
AB - HIV-1 infection enhances HCV replication and as a consequence accelerates HCV-mediated hepatocellular carcinoma (HCC). However, the precise molecular mechanism by which this takes place is currently unknown. Our data showed that infectious HIV-1 failed to replicate in human hepatocytic cell lines. No discernible virus replication was observed, even when the cell lines transfected with HIV-1 proviral DNA were co-cultured with Jurkat T cells, indicating that the problem of liver deterioration in the co-infected patient is not due to the replication of HIV-1 in the hepatocytes of the HCV infected host. Instead, HIV-1 Nef protein was transferred from nef-expressing T cells to hepatocytic cells through conduits, wherein up to 16% (average 10%) of the cells harbored the transferred Nef, when the hepatocytic cells were co-cultured with nefexpressing Jurkat cells for 24 h. Further, Nef altered the size and numbers of lipid droplets (LD), and consistently upregulated HCV replication by 1.5∼2.5 fold in the target subgenomic replicon cells, which is remarkable in relation to the initially indolent viral replication. Nef also dramatically augmented reactive oxygen species (ROS) production and enhanced ethanol-mediated up-regulation of HCV replication so as to accelerate HCC. Taken together, these data indicate that HIV-1 Nef is a critical element in accelerating progression of liver pathogenesis via enhancing HCV replication and coordinating modulation of key intra- and extra-cellular molecules for liver decay.
UR - http://www.scopus.com/inward/record.url?scp=84902682888&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0099545
DO - 10.1371/journal.pone.0099545
M3 - Article
C2 - 24911518
AN - SCOPUS:84902682888
SN - 1932-6203
VL - 9
JO - PLoS ONE
JF - PLoS ONE
IS - 6
M1 - e99545
ER -