title: Maternal-Derived Hepatitis B Virus e Antigen Alters Macrophage Function in Offspring to Drive Viral Persistence after Vertical Transmission.
abstract: In contrast to horizontal transmission of hepatitis B virus (HBV) between adults, which often leads to self-limited acute infection, vertical transmission of HBV from mother to child often leads to chronic infection. However, the mechanisms linking vertical transmission with chronic infection are not known. We developed a mouse model to study the effect of maternal HBV infection on HBV persistence in offspring and found that HBV carried by the mother impaired CD8(+) T cell responses to HBV in her offspring, resulting in HBV persistence. This impairment of CD8(+) T cell responses was mediated by hepatic macrophages, which were predisposed by maternal HBV e antigen (HBeAg) to support HBV persistence by upregulation of inhibitory ligand PD-L1 and altered polarization upon restimulation with HBeAg. Depletion of hepatic macrophages led to CD8(+) T cell activation and HBV clearance in the offspring, raising the possibility of targeting macrophages to treat chronic HBV patients.
authors.affiliation: Department of Molecular Microbiology and Immunology, University of Southern California Keck School of Medicine, Los Angeles, CA 90033, USA.
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Department of Molecular Microbiology and Immunology, University of Southern California Keck School of Medicine, Los Angeles, CA 90033, USA.
authors.forename: Cheng-Fu
authors.initials: CF
authors.lastname: Kuo
authors.affiliation: Department of Molecular Microbiology and Immunology, University of Southern California Keck School of Medicine, Los Angeles, CA 90033, USA.
authors.forename: Omid
authors.initials: O
authors.lastname: Akbari
authors.affiliation: Department of Molecular Microbiology and Immunology, University of Southern California Keck School of Medicine, Los Angeles, CA 90033, USA. Electronic address: jamesou@hsc.usc.edu.
authors.forename: Jing-Hsiung James
authors.initials: JH
authors.lastname: Ou
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D060890:B7-H1 Antigen / Q000235:genetics / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D005260:Female; D005786:Gene Expression Regulation; D006509:Hepatitis B / Q000276:immunology* / Q000635:transmission; D006513:Hepatitis B e Antigens / Q000276:immunology; D006515:Hepatitis B virus / Q000502:physiology*; D006801:Humans; D018445:Infectious Disease Transmission, Vertical; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology* / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000276:immunology*; D019562:Viral Load
chemical_list: D060890:B7-H1 Antigen; D006513:Hepatitis B e Antigens
keywords: HBV e antigen; HBV vertical transmission; Kupffer cells; PD-1; PD-L1; hepatitis B virus