Aß plaques do not protect against HSV-1 infection in a mouse model of familial Alzheimer's disease, and HSV-1 does not induce Aß pathology in a model of late onset Alzheimer's disease.
Brain Pathol
; 33(1): e13116, 2023 01.
Article
in En
| MEDLINE
| ID: mdl-36064300
ABSTRACT
The possibility that the etiology of late onset Alzheimer's disease is linked to viral infections of the CNS has been actively debated in recent years. According to the antiviral protection hypothesis, viral pathogens trigger aggregation of Aß peptides that are produced as a defense mechanism in response to infection to entrap and neutralize pathogens. To test the causative relationship between viral infection and Aß aggregation, the current study examined whether Aß plaques protect the mouse brain against Herpes Simplex Virus 1 (HSV-1) infection introduced via a physiological route and whether HSV-1 infection triggers formation of Aß plaques in a mouse model of late-onset AD that does not develop Aß pathology spontaneously. In aged 5XFAD mice infected via eye scarification, high density of Aß aggregates did not improve survival time or rate when compared with wild type controls. In 5XFADs, viral replication sites were found in brain areas with a high density of extracellular Aß deposits, however, no association between HSV-1 and Aß aggregates could be found. To test whether HSV-1 triggers Aß aggregation in a mouse model that lacks spontaneous Aß pathology, 13-month-old hAß/APOE4/Trem2*R47H mice were infected with HSV-1 via eye scarification with the McKrae HSV-1 strain, intracranial inoculation with McKrae, intracranial inoculation after priming with LPS for 6 weeks, or intracranial inoculation with high doses of McKrae or 17syn + strains that represent different degrees of neurovirulence. No signs of Aß aggregation were found in any of the experimental groups. Instead, extensive infiltration of peripheral leukocytes was observed during the acute stage of HSV-1 infection, and phagocytic activity of myeloid cells was identified as the primary defense mechanism against HSV-1. The current results argue against a direct causative relationship between HSV-1 infection and Aß pathology.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Herpesvirus 1, Human
/
Alzheimer Disease
/
Herpes Simplex
Limits:
Animals
Language:
En
Journal:
Brain Pathol
Journal subject:
CEREBRO
/
PATOLOGIA
Year:
2023
Document type:
Article
Affiliation country:
Estados Unidos