Alzheimer’s Disease (AD) is the sixth leading cause of death in the United States. Recent studies have established a potential link between herpes simplex virus 1 (HSV-1) infection and the development of AD. HSV-1 DNA has been detected in AD amyloid plaques in human brains, and treatment with the antiviral acyclovir (ACV) was reported to block the accumulation of the AD-associated proteins beta-amyloid (Aβ) and hyper-phosphorylated tau (p-tau) in Vero and glioblastoma cells. Our goal was to determine whether the accumulation of AD-related proteins is attributable to acute and/or latent HSV-1 infection in mature hippocampal neurons, a region of the brain severely impacted by AD. Primary adult murine hippocampal neuronal cultures infected with HSV-1, with or without antivirals, were assessed for Aβ and p-tau expression over 7 days postinfection. P-tau expression was transiently elevated in HSV-1-infected neurons, as well as in the presence of antivirals alone. Infected neurons, as well as uninfected neurons treated with antivirals, had a greater accumulation of Aβ42 than uninfected untreated neurons. Furthermore, Aβ42 colocalized with HSV-1 latency-associated transcript (LAT) expression. These studies suggest that p-tau potentially acts as an acute response to any perceived danger-associated molecular pattern (DAMP) in primary adult hippocampal neurons, while Aβ aggregation is a long-term response to persistent threats, including HSV-1 infection. IMPORTANCE Growing evidence supports a link between HSV-1 infection and Alzheimer’s disease (AD). Although AD is clearly a complex multifactorial disorder, an infectious disease etiology provides alternative therapy opportunities for this devastating disease. Understanding the impact that HSV-1 has on mature neurons and the proteins most strongly associated with AD pathology may identify specific mechanisms that could be manipulated to prevent progression of neurodegeneration and dementia.

Two experiments were conducted to corroborate or refute the theory that animals will choose a food that will allow them to use it with maximum efficiency. Pigs have been shown to utilize foods of high nutrient density more efficiently than those of low density, so the choices made by pigs when offered such foods could be used to test the above optimization theory. In experiment 1, 48 Large White × Landrace gilts were used, for an 8-week period starting at 22 kg live weight, while in experiment 2, 48 boars of the same cross but of a genetically improved strain were used from 24 to 60 kg live weight. In both experiments use was made of high nutrient density summit foods which were used alone, or diluted in the ratio 80 summit: 20 milled sunflower husk to provide the low density foods. In experiment 1, the high density diet (HI) contained 7·5 g lysine per kg and 13·20 MJ digestible energy (DE) per kg, whereas in experiment 2 two summit foods were formulated, the first diet (H2) was offered for 3 weeks from 24 kg live weight and the second (H3) followed until 60 kg live weight. Foods H2 and H3 contained 11·0 and 8·40 g lysine per kg respectively and 15·0 and 14·0 MJ DE per kg, respectively. Both experiments made use of a high (H1 and H2, respectively) and a low nutrient density (L1 and L2, respectively) control treatment in which pigs were given ad libitum access to H1 and H2/H3, and L1 and L2/L3 in experiments 1 and 2 respectively (no. =4). In addition, a medium density treatment (Ml) consisting of a 50: 50 mixture of H1 and L1 (no. = 4) was given in experiment 1. Two choice-feeding treatments where used in both experiments, the first in which H1 and H2IH3 were placed in the left bin (CL1 (no. =18) and CL2 (no. = 20), respectively) and the appropriate dilution diet in the right bin, and the second in which H1 and H2/H3 were placed in the right bin (CR1 (no. = 18) and CR2 (no = 20)). There were no differences in average daily growth rates between treatments within experiments but there were significant differences (P < 0·05) in food intakes and efficiency of food utilization (FCE) between treatments. The highest intakes and lowest FCE were obtained on the L1 and L2 treatments while the lowest intakes were recorded on the choice-feeding treatments. There were no significant differences in FCE neither between H1, CL1 and CR1 nor between H2, CL2 and CR2. Only in experiment 1 were there significant differences (P < 0·05) between choice-feeding treatments on the basis of the position of the food bin but there was no preference for a particular position. The results indicated that pigs were able to differentiate successfully between two foods on the basis of their nutrient density, that bin position was not used as a cue in the choice made, that a small amount of the ‘unwanted’ food was consumed throughout the experiment and that the diet selected maximized FCE.

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