title: Distinct patterns of hepcidin and iron regulation during HIV-1, HBV, and HCV infections.
abstract: During HIV type-1 (HIV-1), hepatitis C virus (HCV), and hepatitis B virus (HBV) infections, altered iron balance correlates with morbidity. The liver-produced hormone hepcidin dictates systemic iron homeostasis. We measured hepcidin, iron parameters, cytokines, and inflammatory markers in three cohorts: plasma donors who developed acute HIV-1, HBV, or HCV viremia during the course of donations; HIV-1-positive individuals progressing from early to chronic infection; and chronically HIV-1-infected individuals (receiving antiretroviral therapy or untreated). Hepcidin increased and plasma iron decreased during acute HIV-1 infection, as viremia was initially detected. In patients transitioning from early to chronic HIV-1 infection, hepcidin in the first 60 d of infection positively correlated with the later plasma viral load set-point. Hepcidin remained elevated in individuals with untreated chronic HIV-1 infection and in subjects on ART. In contrast to HIV-1, there was no evidence of hepcidin up-regulation or hypoferremia during the primary viremic phases of HCV or HBV infection; serum iron marginally increased during acute HBV infection. In conclusion, hepcidin induction is part of the pathogenically important systemic inflammatory cascade triggered during HIV-1 infection and may contribute to the establishment and maintenance of viral set-point, which is a strong predictor of progression to AIDS and death. However, distinct patterns of hepcidin and iron regulation occur during different viral infections that have particular tissue tropisms and elicit different systemic inflammatory responses. The hypoferremia of acute infection is therefore a pathogen-specific, not universal, phenomenon.
authors.affiliation: Medical Research Council (MRC) Human Immunology Unit and.
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Armitage
authors.affiliation: Nuffield Department of Medicine, University of Oxford, Oxford OX3 7FZ, United Kingdom;
authors.forename: Andrea R
authors.initials: AR
authors.lastname: Stacey
authors.affiliation: Computational Biology Research Group, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, United Kingdom;
authors.forename: Eleni
authors.initials: E
authors.lastname: Giannoulatou
authors.affiliation: Nuffield Department of Medicine, University of Oxford, Oxford OX3 7FZ, United Kingdom;
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Marshall
authors.affiliation: Department of Biochemistry, Birmingham Heartlands Hospital, Birmingham B9 5SS, United Kingdom;
authors.forename: Pamela
authors.initials: P
authors.lastname: Sturges
authors.affiliation: Department of Biochemistry, Birmingham Heartlands Hospital, Birmingham B9 5SS, United Kingdom;
authors.forename: Kamaljit
authors.initials: K
authors.lastname: Chatha
authors.affiliation: Nuffield Department of Medicine, University of Oxford, Oxford OX3 7FZ, United Kingdom;
authors.forename: Nicola M G
authors.initials: NM
authors.lastname: Smith
authors.affiliation: Center for Infectious Diseases, Beijing You'an Hospital, Capital Medical University, Beijing 100069, China;
authors.forename: XiaoJie
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Medicine, Imperial College, Chelsea and Westminster Hospital, London SW10 9NH, United Kingdom;
authors.forename: XiaoNing
authors.initials: X
authors.lastname: Xu
authors.affiliation: Medical Research Council (MRC) Human Immunology Unit and.
authors.forename: Sant-Rayn
authors.initials: SR
authors.lastname: Pasricha
authors.affiliation: Center for Infectious Diseases, Beijing You'an Hospital, Capital Medical University, Beijing 100069, China;
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.affiliation: Center for Infectious Diseases, Beijing You'an Hospital, Capital Medical University, Beijing 100069, China;
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Biochemistry, Birmingham Heartlands Hospital, Birmingham B9 5SS, United Kingdom;
authors.forename: Craig
authors.initials: C
authors.lastname: Webster
authors.affiliation: MRC International Nutrition Group, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom;
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Prentice
authors.affiliation: Centre for Sexual Health and HIV Research, Mortimer Market Centre, University College London, London WC1 6JB, United Kingdom;
authors.forename: Pierre
authors.initials: P
authors.lastname: Pellegrino
authors.affiliation: Centre for Sexual Health and HIV Research, Mortimer Market Centre, University College London, London WC1 6JB, United Kingdom;
authors.forename: Ian
authors.initials: I
authors.lastname: Williams
authors.affiliation: Blood Systems Research Institute, San Francisco, CA 94118; andDepartments of Laboratory Medicine andMedicine, University of California, San Francisco, CA 94143.
authors.forename: Phillip J
authors.identifier: http://orcid.org/0000-0003-0526-2088
authors.initials: PJ
authors.lastname: Norris
authors.affiliation: Medical Research Council (MRC) Human Immunology Unit and hdrakes@hammer.imm.ox.ac.uk persephone.borrow@ndm.ox.ac.uk.
authors.forename: Hal
authors.initials: H
authors.lastname: Drakesmith
authors.affiliation: Nuffield Department of Medicine, University of Oxford, Oxford OX3 7FZ, United Kingdom; hdrakes@hammer.imm.ox.ac.uk persephone.borrow@ndm.ox.ac.uk.
authors.forename: Persephone
authors.initials: P
authors.lastname: Borrow
mesh_terms: D000209:Acute-Phase Proteins / Q000378:metabolism; D019380:Anti-HIV Agents / Q000627:therapeutic use; D015331:Cohort Studies; D016207:Cytokines / Q000378:metabolism; D015658:HIV Infections / Q000188:drug therapy / Q000378:metabolism*; D015497:HIV-1; D006509:Hepatitis B / Q000378:metabolism*; D006526:Hepatitis C / Q000378:metabolism*; D064451:Hepcidins / Q000378:metabolism*; D007501:Iron / Q000378:metabolism*; D015854:Up-Regulation; D019562:Viral Load
chemical_list: D000209:Acute-Phase Proteins; D019380:Anti-HIV Agents; D016207:Cytokines; D064451:Hepcidins; D007501:Iron
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