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This document is a reply to a letter by Wang et al. regarding the presence of HSV-1 LAT in non-neuronal ganglionic cells of mice and humans. The authors of the reply argue that the original claim made by Wang et al. is unsupported and that their study does not provide sufficient evidence for the conclusion that HSV-1 can establish latency in non-neuronal cells. They also address differences in the methods used for analysis and emphasize the importance of studying both manuscripts and forming one's own conclusions. [Extracted from the article]

Increasing evidence supports the role of neurotropic herpes simplex virus 1 (HSV‐1) in the pathogenesis of Alzheimer's disease (AD). However, it is unclear whether previously reported findings in HSV‐1 cell culture and animal models can be translated to humans. Here, we analyzed clinical specimens from latently HSV‐1 infected individuals and individuals with lytic HSV infection of the brain (herpes simplex encephalitis; HSE). Latent HSV‐1 DNA load and latency‐associated transcript (LAT) expression were identical between trigeminal ganglia (TG) of AD patients and controls. Amyloid β (Aβ) and hyperphosphorylated tau (pTau) were not detected in latently HSV‐infected TG neurons. Aging‐related intraneuronal Aβ accumulations, neurofibrillary tangles (NFT), and/or extracellular Aβ plaques were observed in the brain of some HSE patients, but these were neither restricted to HSV‐infected neurons nor brain regions containing virus‐infected cells. Analysis of unique brain material from an AD patient with concurrent HSE showed that HSV‐infected cells frequently localized close to Aβ plaques and NFT, but were not associated with exacerbated AD‐related pathology. HSE‐associated neuroinflammation was not associated with specific Aβ or pTau phenotypes. Collectively, we observed that neither latent nor lytic HSV infection of human neurons is directly associated with aberrant Aβ or pTau protein expression in ganglia and brain. [ABSTRACT FROM AUTHOR]

Background: To test the hypothesis that varicella-zoster virus (VZV) infection contributes to temporal arteritis pathogenesis, comprehensive in situ analysis was performed on temporal artery biopsies of 38 anterior ischemic optic neuropathy (AION) patients, including 14 (37%) with giant cell arteritis.Methods: Biopsies were completely sectioned, and, on average, 146 serial sections per patient were stained for VZV glycoprotein E.Results: Four of 38 AION patients showed VZV glycoprotein E staining, but VZV infection was not confirmed by staining for VZV IE63 protein and VZV-specific polymerase chain reaction on adjacent sections.Conclusions: This study refutes the premise that VZV is casually related to AION with and without giant cell arteritis. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 induced lower respiratory tract (LRT) disease can deteriorate to acute respiratory distress syndrome (ARDS). Because the release of neutrophil extracellular traps (NETs) is implicated in ARDS pathogenesis, we investigated the presence of NETs and correlates of pathogenesis in blood and LRT samples of critically ill COVID-19 patients. Plasma NET levels peaked early after ICU admission and correlated with SARS-CoV-2 RNA load in sputum and levels of neutrophil-recruiting chemokines and inflammatory markers in plasma. Baseline plasma NET quantity correlated with disease severity, but was not associated with soluble markers of thrombosis nor with development of thrombosis. High NET levels were present in LRT samples and persisted during the course of COVID-19, consistent with the detection of NETs in bronchi and alveolar spaces in lung tissue from fatal COVID-19 patients. Thus, NETs are produced and retained in the LRT of critical COVID-19 patients and could contribute to SARS-CoV-2-induced ARDS pathology.  . [ABSTRACT FROM AUTHOR]

Primary varicella-zoster virus (VZV) infection causes varicella (chickenpox) and the establishment of a lifelong latent infection in ganglionic neurons. VZV reactivates in about one-third of infected individuals to cause herpes zoster, often accompanied by neurological complications. The restricted host range of VZV and, until recently, a lack of suitable in vitro models have seriously hampered molecular studies of VZV latency. Nevertheless, recent technological advances facilitated a series of exciting studies that resulted in the discovery of a VZV latency-associated transcript (VLT) and provide novel insights into our understanding of VZV latency and factors that may initiate reactivation. Deducing the function(s) of VLT and the molecular mechanisms involved should now be considered a priority to improve our understanding of factors that govern VZV latency and reactivation. In this review, we summarize the implications of recent discoveries in the VZV latency field from both a virus and host perspective and provide a roadmap for future studies. [ABSTRACT FROM AUTHOR]

The pathogenesis of enteric zoster, a rare debilitating complication of reactivation of latent varicella-zoster virus (VZV) in the enteric nervous system (ENS), is largely unknown. Infection of monkeys with the closely related Varicellovirus simian varicella virus (SVV) mimics VZV disease in humans. In this study, we determined the applicability of the SVV nonhuman primate model to study Varicellovirus infection of the ENS. We confirmed VZV infection of the gut in latently infected adults and demonstrated that SVV DNA was similarly present in gut of monkeys latently infected with SVV using quantitative real-time PCR. In situ analyses showed that enteric neurons expressed SVV open reading frame (ORF) 63 RNA, but not viral nucleocapsid proteins, suggestive of latent ENS infection. During primary infection, SVV-infected T-cells were detected in gut-draining mesenteric lymph nodes and located in close vicinity to enteric nerves in the gut. Furthermore, flow cytometric analysis of blood from acutely SVV-infected monkeys demonstrated that virus-infected T-cells expressed the gut-homing receptor α4β7 integrin. Collectively, the data demonstrate that SVV infects ENS neurons during primary infection and supports the role of T-cells in virus dissemination to the gut. Because SVV reactivation can be experimentally induced, the SVV nonhuman primate model holds great potential to study the pathogenesis of enteric zoster. [ABSTRACT FROM AUTHOR]