Asymptomatic reactivation and shed of infectious varicella zoster virus in astronauts

Abstract

Varicella zoster virus (VZV) causes varicella (chickenpox), after which virus becomes latent in ganglia along the entire neuraxis. Virus reactivation produces zoster (shingles). Infectious VZV is found in vesicles of patients with zoster and varicella, but virus shed in the absence of disease has not been documented. VZV DNA was previously detected in saliva of astronauts during and after spaceflight, a uniquely stressful environment in which cell mediated immunity (CMI) is temporally dampened. The decline in CMI to VZV associated with zoster led to the hypothesis that infectious VZV would also be present in the saliva of astronauts subjected to stress of space-flight. Herein, not only was the detection of salivary VZV DNA associated with spaceflight validated, but also infectious virus was detected in saliva from 2 of 3 astronauts. This is the first demonstration of shed of infectious VZV in the absence of disease.

Phosphorylation of the Nuclear Form of Varicella-Zoster Virus Immediate-Early Protein 63 by Casein Kinase II at Serine 186

“…Moreover, VZV DNA and infectious virus are present in the saliva of astronauts during and shortly after space flight (11,30), and preliminary investigations suggest that ionizing radiation is the major cause of VZV reactivation in astronauts (S. K. Mehta, personal communication). The cellular localization of CKII catalytic subunits is known to be altered by ionizing radiation (38).…”

A comparison of herpes simplex virus type 1 and varicella-zoster virus latency and reactivation

“…The detection rate for HSV-1 DNA in saliva was found to be *33 % on any given day when individuals were sequentially tested daily for 30 days and, in total, nearly all had detectable HSV-1 DNA in saliva for a duration of 1-3 days in the absence of disease (Kaufman et al, 2005;Miller & Danaher, 2008). VZV DNA and infectious virus can also be detected in saliva from healthy individuals, although under the extreme mental, physical and physiological stress associated with spaceflight (Mehta et al, 2004;Cohrs et al, 2008). Closer to Earth, VZV DNA is present in saliva of *5 % of human immunodeficiency viruspositive individuals on highly active antiretroviral therapy treatment and only rarely (one of 53) in otherwise healthy individuals (Wang et al, 2010).…”

Herpes zoster as a risk factor for stroke and TIA

“…The discovery in recent years that VZV DNA can be detected in oral fluid and blood both in subjects whose rash is outside the head and neck and even in the absence of rash provides a possible explanation. [24][25][26][27] In theory, asymptomatic reactivation of VZV from cranial nerves, detectable as virus in saliva, could also lead to infection of cranial arteries, stroke, and TIA, including in the absence of HZ rash, and when the rash occurs in noncranial dermatomes. 26 This hypothesis is supported by findings from simian varicella virus infection of macaques, a model for VZV.…”

“…In this scenario, control of risk factors that predispose to arterial damage might mitigate the risk from HZ, which in turn might explain our findings that strokes are not more common in UK citizens older than 40 years. Taken together, the finding that virus reacts asymptomatically from cranial nerves, resulting in prolonged oral shedding 24,25,34 particularly in subjects with a history of HZ, 26 and circulation in the blood, 27,34 provides a set of testable hypotheses to explain the increased risk of TIA, MI, and in some cases stroke, persisting for years after an episode of HZ, particularly in the presence of risk factors for vascular disease. The possibility that VZV directly exacerbates preexisting arterial damage would also explain why effective management of risk factors has reduced the incidence of stroke after HZ in the older UK subjects.…”