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. 2019 Aug 27;17(1):286.
doi: 10.1186/s12967-019-2034-9.

Herpes simplex virus-1 (HSV-1) infection induces a potent but ineffective IFN-λ production in immune cells of AD and PD patients

Francesca La Rosa  1 , Simone Agostini  2 , Anna Bianchi  2 , Raffaello Nemni  2 , Federica Piancone  2 , Ivana Marventano  2 , Roberta Mancuso  2 , Marina Saresella  2 , Mario Clerici  2   3
Affiliations

Herpes simplex virus-1 (HSV-1) infection induces a potent but ineffective IFN-λ production in immune cells of AD and PD patients

Francesca La Rosa et al. J Transl Med. .

Abstract

Background: The sequential activation of immediate early (IE), early (E) and late (L) genes is required to allow productive herpes simplex virus type 1 (HSV-1) infection. Several evidences suggest that, together with inflammation, an immunological response incapable to counteract HSV-1 reactivation plays a role in the pathogenesis of Alzheimer's (AD) and Parkinson's (PD) diseases. IFN-lambda (IFN-λ), a cytokine endowed with a robust antiviral activity, contains HSV-1 reactivation. HSV-1-induced IFN-λ, IL-10 and IL-1β as well as the expression of viral IE, E and L genes were analyzed in vitro in peripheral blood mononuclear cells (PBMC) of AD and PD patients as well as of healthy controls (HC).

Methods: PBMC of AD, PD and HC were in vitro infected with one multiplicity of infection (1 MOI) HSV-1. IE, E, and L viral genes transcription as well as IFN-λ, IL-10 and IL-1β production were analyzed.

Results: In HSV-1-infected cells of AD and PD patients compared to HC: (1) transcription of IE (ICP0, ICP27) genes was reduced whereas that of E (UL41, UL29) and L (UL48, LAT) genes was increased; (2) IFN-λ mRNA expression was increased. IL-1β was augmented and IL-10 was reduced in unstimulated cells of AD and PD compared to HC; HSV-1 infection significantly increased IL-10 production in HC alone.

Conclusions: Data herein show that a proinflammatory condition is present in AD and PD, in whom attempts to obstacle viral replication via an initial, possibly more potent IFN-λ-mediated control of IE viral genes is unsuccessful.

Keywords: Alzheimer’s disease; HSV-1; IFN-λ; Immune response; Parkinson’s disease.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
HSV-1 genes expression: Left panels. HSV-1 RL2 (a) and UL54 (b) immediate early (IE) genes. Central panels. HSV-1 UL41 (c) and UL29 (d) early (E) genes. Right panels. HSV-1 UL48 (e) and LATE (f) late (L) genes. HSV-1-infected PBMC of AD and PD patients and Healthy Control (HC) were used to generate the results. Data are expressed as median; statistical significance is shown
Fig. 2
Fig. 2
IFN-λ mRNA-expression and serum concentration. a IFN-λ mRNA expression in HSV-1-infected cells of HSV-1-infected PBMC from AD and PD patients and Healthy Control (HC). b IFN-λ serum concentration in AD and PD patients and Healthy Control (HC). Data are expressed as median, each dot represents IFN-λ gene or protein production by single individual. Statistical significance is shown
Fig. 3
Fig. 3
Cytokines production: IL-1β (upper panels) and IL-10 (lower panels) production by PBMC of AD and PD patients and Healthy Control (HC) that were cultured in medium alone (med) (a, c) or were stimulated with HSV-1 (b, d). Data are expressed as median, each dot represents IL-1β or IL-10 protein production by single individual. Statistical significance is shown
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