Hepatitis B virus evades innate immunity of hepatocytes but activates macrophages during infection

Abstract

Hepatitis B virus (HBV) infects hepatocytes specifically and causes immune mediated liver damage. How HBV interacts with the innate immunity at the early phase of infection, either with the hepatocytes or other cells in the liver remains controversial. To address this question, we utilized various cell culture models and humanized Alb-uPA/SCID mice. All these models were unable to mount an interferon (IFN) response despite robust HBV replication. To elucidate the mechanisms involved in the lack of IFN response, we examined whether HBV actively inhibits innate immune functions of hepatocytes. By treating HBV infected cells with known inducers of IFN signaling pathway, we observed no alteration of either sensing or downstream IFN response by HBV. We showed that the DNA innate sensing pathways are poorly active in hepatocytes, consistent with the muted innate immune recognition of HBV. Upon exposure to high-level HBV, macrophages could be activated with increased inflammatory cytokine expressions. Conclusion: HBV behaves like a "stealth" virus and is not sensed by nor actively interferes with the intrinsic innate immunity of the infected hepatocytes. Macrophages are capable of sensing HBV but require exposure to high HBV titers, potentially explaining the long "window period" during acute infection and HBV's propensity to chronic infection. This article is protected by copyright. All rights reserved.

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