Disturbed Yin–Yang balance: stress increases the susceptibility to primary and recurrent infections of herpes simplex virus type 1

• Published in: Acta pharmaceutica Sinica. B Vol. 10; no. 3; pp. 383 - 398
• Main Authors: Yan, Chang, Luo, Zhuo, Li, Wen, Li, Xue, Dallmann, Robert, Kurihara, Hiroshi, Li, Yi-Fang, He, Rong-Rong
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.03.2020; Elsevier
• Subjects: Herpes simplex virus type 1; HSV-1; Latency; Reactivation; Review; Stress; Susceptibility; LRF; RANKL; Herpes simplex virus type 1; HDACs; HPA axis; CTCF; TRM; HSV-1; PI3K; PNS; LSD1; mTOR; HCF-1; PAMPs; PDK1; AD; Susceptibility; NGF; KLF15; SIRT1; Latency; CORT; IRF3; ORFs; ROS; AMPK; TRIM14; TCM; HPK; PRRs; CNS; sncRNAs; DAMPs; BCL-2; DCs; cGAS; GREs; H3K9; OCT-1; T3; Reactivation; NK cells; MOI; GRs; AKT; Stress; PML; PTMs; ND10; MAVS; REST; TG; TRKA; PRC1; 4E-BP; DEX; CoREST; ICP; TK; CPE; CTL; HPT axis; SGKs; LAT; PML, promyelocytic leukemia protein; DEX, dexamethasone; NGF, nerve growth factor; GRs, glucocorticoid receptors; PTMs, post-translational modifications; TRM, tissue resident memory T cells; LRF, Luman/CREB3 recruitment factor; AMPK, AMP-dependent kinase; mTOR, mammalian target of rapamycin; PDK1, pyruvate dehydrogenase lipoamide kinase isozyme 1; HPA axis, hypothalamo–pituitary–adrenal axis; T3, thyroid hormone; ORFs, open reading frames; 4E-BP, eIF4E-binding protein; SIRT1, sirtuin 1; TCM, traditional Chinese medicine; AD, Alzheimer's disease; AKT, protein kinase B; HSV-1, herpes simplex virus type 1; LSD1, lysine-specific demethylase 1; HPK, herpetic simplex keratitis; NK cells, natural killer cells; CPE, cytopathic effect; DCs, dendritic cells; REST, RE1-silencing transcription factor; SGKs, serum and glucocorticoid-regulated protein kinases; RANKL, receptor activator of NF-κB ligands; OCT-1, octamer binding protein 1; CTCF, CCCTC-binding factor; ROS, reactive oxygen species; GREs, GR response elements; TG, trigeminal ganglia; PRC1, protein regulator of cytokinesis 1; CORT, corticosterone; TRKA, tropomyosin receptor kinase A; DAMPs, damage-associated molecular patterns; H3K9, histone H3 on lysines 9; LAT, latency-associated transcripts; HCF-1, host cell factor 1; ICP, infected cell polypeptide; IRF3, interferon regulatory factor 3; ND10, nuclear domains 10; HDACs, histone deacetylases; PAMPs, pathogen-associated molecular patterns; TK, thymidine kinase; cGAS, cyclic GMP-AMP synthase; BCL-2, B-cell lymphoma 2; PNS, peripheral nervous system; sncRNAs, small non-coding RNAs; MAVS, mitochondrial antiviral-signaling protein; CNS, central nervous system; CoREST, REST corepressor 1; MOI, multiplicity of infection; HPT axis, hypothalamic–pituitary–thyroid axis; CTL, cytotoxic T lymphocyte; TRIM14, tripartite motif-containing 14; PI3K, phosphoinositide 3-kinases; KLF15, Krüppel-like transcription factor 15; PRRs, pattern-recognition receptors
• ISSN: 2211-3835; 2211-3843
• DOI: 10.1016/j.apsb.2019.06.005

Herpes simplex virus type 1 (HSV-1), a neurotropic herpes virus, is able to establish a lifelong latent infection in the human host. Following primary replication in mucosal epithelial cells, the virus can enter sensory neurons innervating peripheral tissues via nerve termini. The viral genome is then transported to the nucleus where it can be maintained without producing infectious progeny, and thus latency is established in the cell. Yin–Yang balance is an essential concept in traditional Chinese medicine (TCM) theory. Yin represents stable and inhibitory factors, and Yang represents the active and aggressive factors. When the organism is exposed to stress, especially psychological stress caused by emotional stimulation, the Yin–Yang balance is disturbed and the virus can re-engage in productive replication, resulting in recurrent diseases. Therefore, a better understanding of the stress-induced susceptibility to HSV-1 primary infection and reactivation is needed and will provide helpful insights into the effective control and treatment of HSV-1. Here we reviewed the recent advances in the studies of HSV-1 susceptibility, latency and reactivation. We included mechanisms involved in primary infection and the regulation of latency and described how stress-induced changes increase the susceptibility to primary and recurrent infections. Following primary infection, HSV-1 establishes latency and reactivates under stress. Stress disturbs inner immune Yin–Yang balance, increasing the susceptibility to HSV-1 infection. In latent infection, stress induces changes in hormone level, chromosomal modification and oxidation, thereby disturbing the Yin–Yang balance between HSV-1 and the host defense, leading to recurrent diseases. [Display omitted]