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Unravelling the immune signature of herpes zoster: Insights into pathophysiology and the HLA risk profile

ABSTRACT: Unravelling the immune signature of herpes zoster: Insights into pathophysiology and the HLA risk profile

PROVIDER: PRJNA1012708 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR25898100.fastq.gz	Fastqsanger.gz
	SRR25898200.fastq.gz	Fastqsanger.gz
	SRR25898300.fastq.gz	Fastqsanger.gz
	SRR25898101.fastq.gz	Fastqsanger.gz
	SRR25898201.fastq.gz	Fastqsanger.gz

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Unravelling the immune signature of herpes zoster: Insights into pathophysiology and the HLA risk profile

Project description:The varicella-zoster virus (VZV) infects over 95% of the population and establishes latency afterwards. Reactivation of VZV causes herpes zoster (HZ), commonly known as shingles, which presents as a painful rash in mostly the elderly and people with a weakened immune system. However, HZ might occur in otherwise healthy individuals too. In this study, we have analyzed the immune signature of HZ to better understand HZ’s pathophysiology. We provide a general overview of the antiviral state and the activation of innate and adaptive immune responses during HZ. An extensive exome-wide association study of HZ, incorporating UK Biobank data across white, black and Asian cohorts highlights the MHC locus as a risk factor for HZ development. Therefore, we conducted one of the largest human leukocyte antigen (HLA) association studies on HZ to date (n=138,701 participants) using Fisher’s exact test and identified five protective and four risk HLA alleles associated with the development of HZ. Additionally, differential gene expression and gene ontology analyses revealed upregulation of several genes and host immune pathways during herpes zoster, especially related to type I interferon response but also involved with adaptive immune responses. Intriguingly, no differences in gene expression were noted during convalescence between HZ patients and controls. Our research reveals that HZ susceptibility is largely governed by a complex pattern of variations in the major histocompatibility complex, resulting in modified antigen recognition in HZ patients. Further, we identified key genes and pathways involved in the host immune response to symptomatic VZV reactivation and provided new molecular insights into the development of HZ and its associated risk factors.

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Project description:Varicella-zoster virus (VZV), an alphaherpesvirus, causes chickenpox (varicella) in young children with an annual minimum of 140 million new cases and herpes zoster in senior, a painful and debilitating disease with 3-5‰ incidence. A complex structural transcriptome of VZV, which numerous novel transcripts, transcript isoforms, and unknown splice events are found during cell infection. Circular RNA (circRNA), a newly important component of the transcriptome, is increasing discoveries of circRNA function in mammalian cells. However, VZV encoded circRNA remains unexplored. The code used in this study and extended data are available from the GitHub repository (https://github.com/ShaominYang/VZV_circRNA)

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Project description:The goal of this study is to characterize the human immune responses to the live attenuated Herpes zoster vaccine Zostavax, to understand the molecular and cellular mechanisms that lead to antibody production and T cell induction, and to understand the difference between young and elderly healthy adults. The overall data collection included antigen specific assays, flow cytometric profiling of innate and adaptive cell populations, measurement of serum cytokines, and transcriptomic and metabolomics signatures. Zostavax induced robust antigen-specific antibody responses, and significant T cell responses. A number of gene pathways were upregulated after vaccination. Using our previously developed blood transcription modules, we also identified transcriptomic correlates to antibody response. Furthermore, this study revealed strong association between PBMC transcriptomics and plasma metabolomics. Integrative analysis of orthogonal datasets from metabolomics, transcriptomic and immune profiling facilitated a temporal reconstruction of Zostavax induced biological networks culminating in antibody responses , and the delineation of novel molecular correlates of vaccine immunity.

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Project description:BackgroundThe incidence of recurrent herpes zoster (HZ) and the relationship between initial and recurrent HZ are not clear.MethodsThe Miyazaki Dermatologist Society has surveyed ~5000 patients with HZ annually since 1997. A questionnaire regarding HZ and its recurrence was completed by the dermatologists.ResultsA total of 34 877 patients with HZ were registered at 43 clinics between June 2009 and November 2015. Among 16 784 patients seen at 10 of the 43 clinics, 1076 patients (6.41%) experienced recurrence. Herpes zoster was more frequent in female than in male patients (5.27 vs 4.25 in 1000 person-years, P < .001), as was HZ recurrence (7.63% vs 4.73%, P < .001). Two and three recurrences were observed in 49 and 3 patients, respectively. Recurrence in the same dermatome was observed in 16.3% of patients, and more frequently this occurred in the left side (P = .027). The number of HZ-experienced persons increased with age, and one third of the population had experienced HZ by the age of 80.ConclusionsRecurrent HZ was observed in 6.41% of patients, with a higher incidence in women. Moreover, HZ experience reduced the HZ incidence to 31.7% of the incidence in the HZ-naive population.

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Herpes zoster.

Project description: Not available

| S-EPMC1889999 | biostudies-literature