Examination of neuro-inflammation and senescence in brainstem of aged mice latently infected with human alphaherpesvirus 1 (HSV-1).

• HSV-1 latently infected mice exhibit enhanced neuroinflammation in brainstem. • Principal sensory nucleus of spinal trigeminal tract (Pr5) of brainstem was examined. • Locus coeruleus (LC) has indirect synaptic connections to Pr5 and was examined. • Neuroinflammation is enhanced in females latently infected with LAT null mutant. • Aged mice generally contained reduced neuroinflammation compared to young mice. Human alphaherpesvirus 1 (HSV-1) establishes life-long latency in sensory neurons in trigeminal ganglia (TG), brainstem neurons, and other CNS neurons. Two important segments of the brainstem were examined in this study: principal sensory nucleus of the spinal trigeminal tract (Pr5) because it receives direct afferent inputs from TG, and locus coeruleus (LC) because it is indirectly connected to Pr5 and LC sends axonal projections to cortical structures, which may facilitate viral spread from brainstem to the brain. The only viral gene abundantly expressed during latency is the latency associated transcript (LAT). Previous studies revealed 8-week old female C57Bl/6 mice infected with a LAT null mutant (dLAT2903) versus wild-type (wt) HSV-1 exhibit higher levels of senescence markers and inflammation in LC of females. New studies revealed 1-year old mice latently infected with wt HSV-1 or dLAT2903 contained differences in neuroinflammation and senescence in Pr5 and LC versus young mice. In summary, these studies confirm HSV-1 promotes neuro-inflammation in the brainstem, which may accelerate neurodegenerative disease. [Display omitted] [ABSTRACT FROM AUTHOR]