Evidence indicates that herpes simplex virus (HSV) participates in the pathogenesis of Alzheimer\'s disease (AD).
We investigated AD and dementia risks according to the presence of herpesvirus antibodies in relation to anti-herpesvirus treatment and potential APOE ɛ4 carriership interaction.
This study was conducted with 1002 dementia-free 70-year-olds living in Sweden in 2001-2005 who were followed for 15 years. Serum samples were analyzed to detect anti-HSV and anti-HSV-1 immunoglobulin (Ig) G, anti-cytomegalovirus (CMV) IgG, anti-HSV IgM, and anti-HSV and anti-CMV IgG levels. Diagnoses and drug prescriptions were collected from medical records. Cox proportional-hazards regression models were applied.
Cumulative AD and all-cause dementia incidences were 4% and 7%, respectively. Eighty-two percent of participants were anti-HSV IgG carriers, of whom 6% received anti-herpesvirus treatment. Anti-HSV IgG was associated with a more than doubled dementia risk (fully adjusted hazard ratio = 2.26, p = 0.031). No significant association was found with AD, but the hazard ratio was of the same magnitude as for dementia. Anti-HSV IgM and anti-CMV IgG prevalence, anti-herpesvirus treatment, and anti-HSV and -CMV IgG levels were not associated with AD or dementia, nor were interactions between anti-HSV IgG and APOE ɛ4 or anti-CMV IgG. Similar results were obtained for HSV-1.
HSV (but not CMV) infection may be indicative of doubled dementia risk. The low AD incidence in this cohort may have impaired the statistical power to detect associations with AD.

OBJECTIVE: Neonatal infection by herpes simplex virus (HSV) 1 or 2 presents a devastating burden to new parents, due to the unpredictability of severe clinical outcomes, as well as the potential for lifelong reactivation. While just under half of neonatal HSV infections have mild clinical impacts akin to those observed in adults, the other half experience viral spread throughout the body (disseminated infection) and/or the brain (central nervous system infection).
CONCLUSIONS: Here we summarize current data on clinical diagnostic measures, antiviral therapy, and known factors of human host biology that contribute to the distinct neonatal outcomes of HSV infection.
RESULTS: We then explore recent new data on how viral genetic diversity between infections may impact clinical outcomes. Further research will be critical to build upon these early findings and to provide statistical power to our ability to discern and/or predict the potential clinical path of a given neonatal infection.

OBJECTIVE: To investigate the effect of lipopolysaccharide (LPS) on human herpesvirus 1 (HHV-1) infection in epithelial cells.
METHODS: Two strains of HHV-1, HHV-1 F strain (HHV-1f) and HHV-1 strain-H129 with GFP knock-in (HHV-g4), were used to infect HCE-T and VERO cells at MOIs of 0.04 and 0.02, respectively. After 1 h, 0, 10, 50, and 100 μg/ml LPS was added to serum-free medium and the cells were cultured for up to 24 h. GFP fluorescence of HHV-g4 in cells was examined under a fluorescence microscope and imaged. HHV-1f titer was determined by quantitative real-time polymerase chain reaction (qPCR) in HCE-T cells and plaque assays in VERO cells. The expression of the viral ICP4 protein of HHV-1f was detected by Western blot assay. IL-6 and IL-10 levels in culture medium were determined by enzyme-linked immunosorbent assay (ELISA).
RESULTS: Similar changes but at different degrees were found in HCE-T and VERO cells that were infected with HHV-1. GFP fluorescence of HHV-g4 and cell lesions increased in a dose-dependent manner. Virus titer was also enhanced by LPS stimulation in HCE-T and VERO cells. ICP4 expression was promoted at higher LPS concentrations (P = 0.04). In addition, viral infection resulted in increased expression of IL-6 in a dose-dependent manner at 12 and 24 h (P = 0.01), while IL-10 expression was unaffected by either HHV-1 infection or LPS stimulation.
CONCLUSIONS: LPS promotes HHV-1 infection in epithelial cells, which suggests that gram-negative bacteria on ocular surfaces may aggravate HHV-1 infection.

In this study, we used the amplified isoform sequencing technique from Pacific Biosciences to characterize the poly(A)+ fraction of the lytic transcriptome of the herpes simplex virus type 1 (HSV-1). Our analysis detected 34 formerly unidentified protein-coding genes, 10 non-coding RNAs, as well as 17 polycistronic and complex transcripts. This work also led us to identify many transcript isoforms, including 13 splice and 68 transcript end variants, as well as several transcript overlaps. Additionally, we determined previously unascertained transcriptional start and polyadenylation sites. We analyzed the transcriptional activity from the complementary DNA strand in five convergent HSV gene pairs with quantitative RT-PCR and detected antisense RNAs in each gene. This part of the study revealed an inverse correlation between the expressions of convergent partners. Our work adds new insights for understanding the complexity of the pervasive transcriptional overlaps by suggesting that there is a crosstalk between adjacent and distal genes through interaction between their transcription apparatuses. We also identified transcripts overlapping the HSV replication origins, which may indicate an interplay between the transcription and replication machineries. The relative abundance of HSV-1 transcripts has also been established by using a novel method based on the calculation of sequencing reads for the analysis.