La Rosa F, Agostini S, Bianchi A, Nemni R, Piancone F, Marventano I, Mancuso R, Saresella M, Clerici M. Herpes simplex virus-1 (HSV-1) infection induces a potent but ineffective IFN-λ production in immune cells of AD and PD patients. J Transl Med. 2019 Aug 27;17(1):286. PubMed.
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University of Edinburgh
Do AD/PD Leukocytes Respond Differently to Herpesvirus Infection?
This recent paper may address why some of us come down with AD/PD, and others do not. The researchers took blood from AD/PD patients and age-matched controls (all HSV-1-positive), prepared PBMCs, and infected them in vitro with HSV-1. There were striking differences in their responses to infection.
The authors studied two specific parameters: induction of cytokines including interferon lambda (IFN-λ, also known as IL-28/29), an atypical IFN associated with defense against HSV (Zhou et al., 2011; Griffiths et al., 2013), and profiles of early/late viral gene expression.
Levels of antiviral IFN-λ mRNA were more than 10-fold higher following HSV-1 infection of patient versus control PBMCs. AD/PD patient blood cells also showed enhanced HSV-1 late gene expression versus controls, but reduced early gene expression (La Rosa et al., 2019), pointing to differential activation of viral replicative versus latency pathways. Muddying analysis, the assays could have detected endogenous HSV-1 sequences (all subjects were HSV-1-positive),
Why might AD/PD lymphocytes respond differently to infection? APOE genotype can modulate immune cell function (Konttinen et al., 2019), reiterating some of the findings of La Rosa et al. The physiological host environment could also play a role: HSV-1 can be reactivated by stress (Padgett et al., 1998), and widespread environmental toxins such as dioxins can activate the aryl hydrocarbon receptor (AHR) to trigger emergence of HSV-1 from a latent to a replicative state (Tsyrlov et al., 2017). CMV (that can reactivate HSV) may be hypersensitive to dioxin reactivation (Murayama et al., 2002). Evidently, both host genotype and physiological/toxicological status could play a role.
This work raises the intriguing prospect that we can study key aspects of AD/PD in something as simple as a blood sample. A key question: Does the difference between AD/PD PBMCs and controls only emerge after disease emergence, or are there diagnostic implications?
— Ilya Tsyrlov, Ilya B. Tsyrlov, President and Chief Scientific Officer of XENOTOX, Inc., is the co-author of this comment.
References:
La Rosa F, Agostini S, Bianchi A, Nemni R, Piancone F, Marventano I, Mancuso R, Saresella M, Clerici M. Herpes simplex virus-1 (HSV-1) infection induces a potent but ineffective IFN-λ production in immune cells of AD and PD patients. J Transl Med. 2019 Aug 27;17(1):286. PubMed.
Zhou L, Li J, Wang X, Ye L, Hou W, Ho J, Li H, Ho W. IL-29/IL-28A suppress HSV-1 infection of human NT2-N neurons. J Neurovirol. 2011 Jun;17(3):212-9. Epub 2011 Apr 16 PubMed.
Griffiths SJ, Koegl M, Boutell C, Zenner HL, Crump CM, Pica F, Gonzalez O, Friedel CC, Barry G, Martin K, Craigon MH, Chen R, Kaza LN, Fossum E, Fazakerley JK, Efstathiou S, Volpi A, Zimmer R, Ghazal P, Haas J. A systematic analysis of host factors reveals a Med23-interferon-λ regulatory axis against herpes simplex virus type 1 replication. PLoS Pathog. 2013;9(8):e1003514. Epub 2013 Aug 8 PubMed.
Konttinen H, Cabral-da-Silva ME, Ohtonen S, Wojciechowski S, Shakirzyanova A, Caligola S, Giugno R, Ishchenko Y, Hernández D, Fazaludeen MF, Eamen S, Budia MG, Fagerlund I, Scoyni F, Korhonen P, Huber N, Haapasalo A, Hewitt AW, Vickers J, Smith GC, Oksanen M, Graff C, Kanninen KM, Lehtonen S, Propson N, Schwartz MP, Pébay A, Koistinaho J, Ooi L, Malm T. PSEN1ΔE9, APPswe, and APOE4 Confer Disparate Phenotypes in Human iPSC-Derived Microglia. Stem Cell Reports. 2019 Oct 8;13(4):669-683. Epub 2019 Sep 12 PubMed.
Padgett DA, Sheridan JF, Dorne J, Berntson GG, Candelora J, Glaser R. Social stress and the reactivation of latent herpes simplex virus type 1. Proc Natl Acad Sci U S A. 1998 Jun 9;95(12):7231-5. PubMed.
Tsyrlov IB, Shur IN, Applebaum JG, Wu JS. AHR–ARNT signaling pathway mediates transcriptional activation of HSV-1 in glial cells: a pathogenic factor that might affect AD development. Alzheimer's & Dementia, July 2017
Murayama T, Inoue M, Nomura T, Mori S, Eizuru Y. 2,3,7,8-Tetrachlorodibenzo-p-dioxin is a possible activator of human cytomegalovirus replication in a human fibroblast cell line. Biochem Biophys Res Commun. 2002 Aug 23;296(3):651-6. PubMed.
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