Distinct patterns of hepcidin and iron regulation during HIV-1, HBV, and HCV infections

Abstract

Significance Altered iron levels correlate with disease progression in HIV type-1 (HIV-1) infection, and cellular iron promotes HIV-1 replication. In chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, increased liver iron levels contribute to disease. The peptide hormone hepcidin controls iron distribution. We find that hepcidin increases during the acute phase of HIV-1 infection, early hepcidin predicts later plasma viral set-point, and hepcidin remains high even in chronically infected individuals receiving antiretroviral therapy. Conversely hepcidin is not induced, and blood iron is not decreased, during the acute response to HBV and HCV. Therefore, the nature of iron redistribution during the response to infections is a pathogen-specific phenomenon; furthermore, the deleterious effects of chronic infection on hepcidin and iron appear to be established early in infection.

Short Communication: High Cellular Iron Levels Are Associated with Increased HIV Infection and Replication

“…Altered hepcidin expression has been described in hepatitis B and hepatitis C infection, 43,44 but observations of changes in hepcidin levels in HIV infection are conflicting. Hepcidin levels were shown to be increased in HIV infection with or without ART, which is consistent with reduced serum iron levels, 45 but another study demonstrated reduced hepcidin levels in HIV-positive women, which can lead to increased iron release into the circulation. 46 Our results are more consistent with reduced hepcidin levels leading to increased serum iron, although we did not measure hepcidin levels in our studies.…”

Iron homeostasis in host defence and inflammation

“…Interestingly, although most bacterial and some viral infections (such as influenza virus and HIV) rapidly increase hepcidin production in humans and mouse models, hepatitis B and hepatitis C virus infections fail to elicit systemic inflammatory responses and hepcidin production 30 . The consequences of the altered inflammatory and iron responses for infections with these liver-tropic viruses remain to be determined.…”

Hepcidin regulation in the anemia of inflammation

“…For example, while many infections upregulate hepcidin and induce hypoferremia, hepatits B and hepatitis C viruses do not elicit a systemic inflammatory response or induce hepcidin or hypoferremia [36]. …”