LITERATURE UPDATE
over. No serious sequelae of disease such as pneumonitis, hepatitis, encephalitis, or meningitis occurred, and she made a complete recovery. There are individual and
community-wide benefits to childhood immunisation against varicella. This case highlights an unusual presentation of disseminated vaccine-strain herpes zoster in an adolescent with secondary immunodeficiency 11 years after completing primary immunisation. In addition, this case informs paediatricians of complications that can arise in immunised subjects if they become immunosuppressed years later. The only way to distinguish between wild- type and vaccine-strain herpes zoster was by viral genotyping. Providers should be cognisant of potential vaccine virus reactivation in their differential. Considerations for work-up and management should include infection control and viral resistance in refractory cases.
Varicella zoster virus-induced autophagy in human neuronal and hematopoietic cells exerts antiviral activity
Heinz JL, Hinke DM, Maimaitili M et al. J Med Virol. 2024 Jun;96(6):e29690. doi: 10.1002/jmv.29690.
Autophagy is a degradational pathway with pivotal roles in cellular homeostasis and survival, including protection of neurons in the central nervous system (CNS). The significance of autophagy as antiviral defence mechanism is recognised and some viruses hijack and modulate this process to their advantage in certain cell types.
In this study, the authors present data demonstrating that the human neurotropic herpesvirus varicella zoster virus (VZV) induces autophagy in human SH-SY5Y neuronal cells, in which the pathway exerts antiviral activity. Productively VZV-infected SH-SY5Y cells showed increased LC3-I-LC3-II conversion as well as co-localisation of the viral glycoprotein E and the autophagy receptor p62. The activation of autophagy was dependent on a functional viral genome. Interestingly, inducers of autophagy reduced viral transcription, whereas inhibition of autophagy increased viral transcript expression. Finally, the genotype of patients with
severe ocular and brain VZV infection were analysed to identify potential autophagy-associated inborn errors of immunity. Two patients expressing genetic variants in the autophagy genes ULK1 and MAP1LC3B2, respectively, were
identified. Notably, cells of both patients showed reduced autophagy, alongside enhanced viral replication and death of VZV-infected cells. In conclusion, these results demonstrate a neuro-protective role for autophagy in the context of VZV infection and suggest that failure to mount an autophagy response is a potential predisposing factor for development of severe VZV disease.
Primary immunodeficiency-related genes and varicella-zoster virus reactivation syndrome: a Mendelian randomization study Wang H, Chen G, Gong Q, Wu J, Chen P. Front Immunol. 2024 Aug 26;15:1403429. doi: 10.3389/fimmu.2024.1403429. eCollection 2024.
Currently, evidence regarding the causal relationship between primary immunodeficiency-related genes and varicella-zoster virus reactivation syndrome is limited and inconsistent. Therefore, this study employs Mendelian randomisation (MR) methodology to investigate the causal relationship between the two.
The authors selected 110 single- nucleotide polymorphisms (SNPs) of primary immunodeficiency-related genes as instrumental variables (IVs). Genetic associations of primary immunodeficiency-related genes were derived from recent genome- wide association studies (GWAS) data on human plasma protein levels and circulating immune cells. Data on genes associated with varicella-zoster virus reactivation syndrome were obtained from the GWAS Catalogue and FINNGEN database, primarily analysed using inverse variance weighting (IVW) and sensitivity analysis. Through MR analysis, the authors
identified nine primary immunodeficiency- related genes causally associated with herpes zoster and its subsequent neuralgia; determined causal associations of 20 primary immunodeficiency-related genes with three vascular lesions (stroke, cerebral aneurysm, giant cell arteritis); revealed causal associations of 10 primary immunodeficiency-related genes with two ocular diseases (retinopathy, keratitis); additionally, three primary immunodeficiency-related genes each were associated with encephalitis, cranial nerve palsy, and gastrointestinal infections.
This study discovers a certain association between primary immunodeficiency-related genes and varicella-zoster virus reactivation syndrome, yet further investigations
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are warranted to explore the specific mechanisms underlying these connections.
Herpes Zoster Recurrence: A Narrative Review of the Literature Parikh R, Spence O, Giannelos N, Kaan I. Dermatol Ther (Heidelb). 2024 Mar;14(3):569-592. doi: 10.1007/s13555-024-01101-7.
Herpes zoster (HZ; shingles) is a painful, cutaneous disease caused by reactivation of the varicella zoster virus, which causes varicella (chickenpox) typically during childhood. The considerable healthcare burden of HZ is relatively well documented, with approximately one in three individuals experiencing at least one episode during their lifetime, debilitating symptoms including neuropathic pain, and complications such as post-herpetic neuralgia, vision loss, and rarely, stroke, and increased severity in immunocompromised individuals. However, the authors are not aware of a comprehensive review of literature specifically examining the burden of HZ recurrence. A PubMed search (1 January 2003-2 February 2023) was conducted to assess available literature on the incidence, risk factors, and clinical features of HZ recurrence.
The incidence of HZ recurrence
reported by the studies identified was wide ranging. Studies in general populations of immunocompetent or immunocompetent/immunosuppressed (mixed) populations with an initial HZ episode estimate that approximately 1.2 – 9.6% of individuals may experience HZ recurrence, with an incidence rate of 1.7 – 16.6 cases per 1000 person-years. HZ recurrence was reported in 0.0 – 18.2% of immunocompromised individuals with HZ, with an incidence rate of 17.0 – 55 cases per 1000 person-years. Incidence rates varied according to study design, follow- up, and study populations. Recognised risk factors for HZ recurrence include immunocompromised status, female sex, family history, and comorbidities such as diabetes. Other factors that may predispose individuals to recurrence include long-lasting pain after the initial HZ episode, and the presence of herpes zoster ophthalmicus. This review underlines that following an initial HZ episode, individuals remain at risk of HZ recurrence, adding to the disease burden in a population. As HZ is preventable by vaccination, national HZ vaccination recommendations should include the need for, and timing of, vaccination both in immunocompetent and immunocompromised individuals who have a history of HZ.
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