Effect of HSV-1 latent infection on laser-induced axotomy
Abstract
Over 20% of military personnel evacuated from Iraq and Afghanistan conflicts have had some type of blast-induced neurotrauma (BINT; Warden, 2006). These soldiers have been diagnosed with cognitive and psychiatric disorders at increasing rates (Jett, 2010). One such pathology of BINT is the disruption of the blood-brain barrier. A damaged blood-brain barrier increases the likelihood of circulating pathogens to enter the central nervous system to produce insults to the brain. One such pathogen that is naturally attracted to neurons is Herpes Simplex Virus Type I (HSV-1). Over 60% of the US population is infected with HSV-1 (Xu et al., 2006). Alarmingly, the incidence of viral infect infections such as HSV-1 is higher among military personnel than civilians (Goyal et al., 2012). HSV-1 continues to be a leading infectious cause of corneal blindness and acute, sporadic encephalitis (Al-Dujaili et al., 2011). Additionally, HSV-1 infection has been linked with cognitive deficiencies, including an increased risk of developing dementia (Tarter et al., 2014; Lovheim et al., 2015) Wozniak and colleagues demonstrated that HSV-1 prompts the accumulation of amyloid beta plaques and neurofibrillary tangles, two pathological hallmarks of dementia and neurological damage induced by blast-induced neurotrauma (BINT) (Wozniak et al., 2011). Taken together, these data support a central hypothesis that an existing infection of HSV-1 will exacerbate the cellular pathologies induced by mild shockwave-related BINT. This hypothesis will be tested via the following objective. Objective 1. Test the hypothesis that a latent HSV-1 infection leads to aggravated cellular pathologies associated with BINT. Both clinical and basic research findings demonstrate the possibility of HSV-1 to precipitate neuronal damage and cognitive deficits (Wozniak et al., 2011; Tarter et al., 2014). Yet, the role of HSV-1 in exacerbating the cellular damage induced by BINT is nuclear In this objective, primary sensory neurons will be exposed to laser treatment in an effort to model axonal damage produced by BINT. The proposal predicts that laser-treated neurons latently with HSV-1 will exhibit higher rates of cytopathy and dementia-related pathology compared to uninfected neurons subjected to the laser alone. Relationship to Army s Mission: This Short-Term Innovative Research award would allow me to build a research arm in my laboratory focused on the intersection of BINT and viral infection. With this in mind, results from this work would influence both pre-deployment screening and treatment to limit the exacerbating effects of preexisting HSV-1 infections, particularly in soldiers most at risk to terrorist explosive events. Given that the PI performs research at an exclusively undergraduate institution, this award would augment the "fostering of scientists....training in the disciplines critical to Army needs."
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- May 07, 2018
- Source ID
- W911NF1710559
Entities
People
- Gerald Griffin
Organizations
- Army Contracting Command
- Hope College
- United States Army