title: Innate and Adaptive Immune Regulation During Chronic Viral Infections.
abstract: Chronic viral infections represent a unique challenge to the infected host. Persistently replicating viruses outcompete or subvert the initial antiviral response, allowing the establishment of chronic infections that result in continuous stimulation of both the innate and adaptive immune compartments. This causes a profound reprogramming of the host immune system, including attenuation and persistent low levels of type I interferons, progressive loss (or exhaustion) of CD8(+) T cell functions, and specialization of CD4(+) T cells to produce interleukin-21 and promote antibody-mediated immunity and immune regulation. Epigenetic, transcriptional, posttranscriptional, and metabolic changes underlie this adaptation or recalibration of immune cells to the emerging new environment in order to strike an often imperfect balance between the host and the infectious pathogen. In this review we discuss the common immunological hallmarks observed across a range of different persistently replicating viruses and host species, the underlying molecular mechanisms, and the biological and clinical implications.
authors.affiliation: Molecular Biology Section, Division of Biological Sciences, University of California, San Diego, La Jolla, California 92093; email: eizuniga@ucsd.edu.
authors.forename: Elina I
authors.initials: EI
authors.lastname: Zuniga
authors.affiliation: Molecular Biology Section, Division of Biological Sciences, University of California, San Diego, La Jolla, California 92093; email: eizuniga@ucsd.edu.
authors.forename: Monica
authors.initials: M
authors.lastname: Macal
authors.affiliation: Molecular Biology Section, Division of Biological Sciences, University of California, San Diego, La Jolla, California 92093; email: eizuniga@ucsd.edu.
authors.forename: Gavin M
authors.initials: GM
authors.lastname: Lewis
authors.affiliation: Section of Inflammation, Repair and Development, National Heart and Lung Institute, Imperial College London, London SW7 2AZ, United Kingdom.
authors.forename: James A
authors.initials: JA
authors.lastname: Harker
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D006801:Humans; D007113:Immunity, Innate; D014777:Virus Diseases / Q000235:genetics / Q000276:immunology* / Q000821:virology*; D018406:Virus Physiological Phenomena; D014780:Viruses / Q000235:genetics / Q000276:immunology*
keywords: HCV; HIV; LCMV; T cells; chronic viral infection; interferon