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      Mechanisms of Adaptive Immunity to Porcine Reproductive and Respiratory Syndrome Virus

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          Abstract

          The adaptive immune response is necessary for the development of protective immunity against infectious diseases. Porcine reproductive and respiratory syndrome virus (PRRSV), a genetically heterogeneous and rapidly evolving RNA virus, is the most burdensome pathogen of swine health and wellbeing worldwide. Viral infection induces antigen-specific immunity that ultimately clears the infection. However, the resulting immune memory, induced by virulent or attenuated vaccine viruses, is inconsistently protective against diverse viral strains. The immunological mechanisms by which primary and memory protection are generated and used are not well understood. Here, we summarize current knowledge regarding cellular and humoral components of the adaptive immune response to PRRSV infection that mediate primary and memory immune protection against viruses.

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          Recapitulating adult human immune traits in laboratory mice by normalizing environment

          Lalit Beura, Sara Hamilton, Kevin Bi … (2016)
          Our current understanding of immunology was largely defined in laboratory mice because of experimental advantages including inbred homogeneity, tools for genetic manipulation, the ability to perform kinetic tissue analyses starting with the onset of disease, and tractable models. Comparably reductionist experiments are neither technically nor ethically possible in humans. Despite revealing many fundamental principals of immunology, there is growing concern that mice fail to capture relevant aspects of the human immune system, which may account for failures to translate disease treatments from bench to bedside 1–8 . Laboratory mice live in abnormally hygienic “specific pathogen free” (SPF) barrier facilities. Here we show that the standard practice of laboratory mouse husbandry has profound effects on the immune system and that environmental changes result in better recapitulation of features of adult humans. Laboratory mice lack effector-differentiated and mucosally distributed memory T cells, which more closely resembles neonatal than adult humans. These cell populations were present in free-living barn populations of feral mice, pet store mice with diverse microbial experience, and were induced in laboratory mice after co-housing with pet store mice, suggesting a role for environment. Consequences of altering mouse housing profoundly impacted the cellular composition of the innate and adaptive immune system and resulted in global changes in blood cell gene expression patterns that more closely aligned with immune signatures of adult humans rather than neonates, altered the mouse’s resistance to infection, and impacted T cell differentiation to a de novo viral infection. These data highlight the impact of environment on the basal immune state and response to infection and suggest that restoring physiological microbial exposure in laboratory mice could provide a relevant tool for modeling immunological events in free-living organisms, including humans.
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            Rational HIV immunogen design to target specific germline B cell receptors.

            Joseph Jardine, Jean-Philippe Julien, Sergey Menis … (2013)
            Vaccine development to induce broadly neutralizing antibodies (bNAbs) against HIV-1 is a global health priority. Potent VRC01-class bNAbs against the CD4 binding site of HIV gp120 have been isolated from HIV-1-infected individuals; however, such bNAbs have not been induced by vaccination. Wild-type gp120 proteins lack detectable affinity for predicted germline precursors of VRC01-class bNAbs, making them poor immunogens to prime a VRC01-class response. We employed computation-guided, in vitro screening to engineer a germline-targeting gp120 outer domain immunogen that binds to multiple VRC01-class bNAbs and germline precursors, and elucidated germline binding crystallographically. When multimerized on nanoparticles, this immunogen (eOD-GT6) activates germline and mature VRC01-class B cells. Thus, eOD-GT6 nanoparticles have promise as a vaccine prime. In principle, germline-targeting strategies could be applied to other epitopes and pathogens.
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              Humoral immunity due to long-lived plasma cells.

              Mark Slifka, Rustom Antia, Jason Whitmire … (1998)
              Conventional models suggest that long-term antibody responses are maintained by the continuous differentiation of memory B cells into antibody-secreting plasma cells. This is based on the notion that plasma cells are short-lived and need to be continually replenished by memory B cells. We examined the issue of plasma cell longevity by following the persistence of LCMV-specific antibody and plasma cell numbers after in vivo depletion of memory B cells and by adoptive transfer of virus-specific plasma cells into naive mice. The results show that a substantial fraction of plasma cells can survive and continue to secrete antibody for extended periods of time (>1 year) in the absence of any detectable memory B cells. This study documents the existence of long-lived plasma cells and demonstrates a new mechanism by which humoral immunity is maintained.
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                Author and article information

                Contributors
                Linda Dixon: Role: Academic Editor
                Simon Graham: Role: Academic Editor
                Journal
                Journal ID (nlm-ta): Viruses
                Journal ID (iso-abbrev): Viruses
                Journal ID (publisher-id): viruses
                Title: Viruses
                Publisher: MDPI
                ISSN (Electronic): 1999-4915
                Publication date (Electronic): 13 June 2017
                Publication date Collection: June 2017
                Volume: 9
                Issue: 6
                Electronic Location Identifier: 148
                Affiliations
                Department of Veterinary and Biomedical Sciences, University of Minnesota, 1971 Commonwealth Avenue, St. Paul, MN 55108, USA; murta001@ 123456umn.edu
                Author notes
                [* ]Correspondence: rahex008@ 123456umn.edu ; Tel.: +1-563-599-7268
                Article
                Publisher ID: viruses-09-00148
                DOI: 10.3390/v9060148
                PMC ID: 5490824
                PubMed ID: 28608816
                SO-VID: 5c9596f1-7bc4-40dc-8127-8b3aaaa0682c
                Copyright © © 2017 by the authors.
                License:

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 31 March 2017
                Date accepted : 07 June 2017
                Categories
                Subject: Review

                ScienceOpen disciplines: Microbiology & Virology
                Keywords: prrsv,t cell,b cell,nk cell,neutralizing antibody,porcine,memory,adaptive immune response
                Data availability:
                ScienceOpen disciplines: Microbiology & Virology
                Keywords: prrsv, t cell, b cell, nk cell, neutralizing antibody, porcine, memory, adaptive immune response

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