تاثیرات آسیکلوویر و IVIG بر پیامدهای رفتاری بعد از عفونت HSV1 CNS Effects of Acyclovir and IVIG on Behavioral Outcomes after HSV1 CNS Infection

1. Introduction Herpes simplex virus type 1 is a highly contagious neurotropic alpha herpesvirus with global prevalence estimates for latent infections exceeding 85% for adults 60 and older [1]. Latent HSV resides in sensory ganglionic neurons and other synaptically contiguous CNS neurons in a nonreplicating, transcriptionally repressed state. HSV is the major cause of sporadic encephalitis resulting from primary infections in newborns and/or from reactivation of latent virus in adults. While vastly improved diagnostic procedures combined with safe and effective antiviral therapies have significantly improved outcomes, mortality (~25%) and the incidence of debilitating neurological disabilities in survivors remain unacceptably high [2–4]. Typically, HSE is focal, involving the medial temporal lobe, and it usually runs an acute course [5]. Anatomically and functionally, long-term damage from HSE is usually confined to the limbic system though the reason is unclear, but speculation is that it relates to HSV entering the CNS via the olfactory bulb and/or the trigeminal nerve or possibly to some specific permissiveness or affinity of the limbic cortices for HSV [6–8]. Following intranasal inoculation of mice, HSV spreads via the olfactory and trigeminal routes to the piriform cortex, thalamus, amygdaloid nucleus, and medial hypothalamic nuclei which comprise the limbic region of the brain that is known to support a variety of functions including memory, emotion, behavior, and olfaction [9–13]. Importantly, inflammatory lesions and prolonged inflammatory infiltrates in these brain areas have been correlated with memory impairment in untreated mice surviving HSV infection [13], which establishes the utility of this model of HSE for exploring immunomodulatory treatments that could ameliorate long-term neurological deficits in humans as prolonged antiviral treatment failed to improve outcomes [14].