Figure 2

CCL2-mediated synergistic effects of HIV/HCV co-infection on liver fibrosis. Proposed model explains migration of HIV into the liver to infect or activate Kupffer cells, hepatocytes and HSCs directly or indirectly via ROS and TGF-β, to create CCL2 rich inflammatory milieu. CCL2 may act on HSC in a positive feed-back loop manner to accelerate fibrosis via myofibroblast and collagen synthesis. Elevated CCL2 in the liver could also recruit HIV permissive CD4⁺ T cells and monocytes into the liver for next round of virus replication in a positive feed-back loop manner. This leads to persistence of a high HIV viremia. In addition, elevated CCL2 can polarize helper T cells (Th0) cells into IL-4 and IL-10 secreting Th2 phenotype, a strong determinant HIV disease progression. Further, CCL2 can induce CD4⁺ T cells to express higher levels of CXCR4, an HIV co-receptor. Overall this scheme depicts how a complex cellular interactions and virus cross-talks via CCL2 can potentially drive hepatic fibrosis HIV replication in HIV/HCV co-infection scenario.