| First Author | Bocharova OV | Year | 2023 |
| Journal | Brain Pathol | Volume | 33 |
| Issue | 1 | Pages | e13116 |
| PubMed ID | 36064300 | Mgi Jnum | J:350549 |
| Mgi Id | MGI:7663149 | Doi | 10.1111/bpa.13116 |
| Citation | Bocharova OV, et al. (2023) Abeta plaques do not protect against HSV-1 infection in a mouse model of familial Alzheimer's disease, and HSV-1 does not induce Abeta pathology in a model of late onset Alzheimer's disease. Brain Pathol 33(1):e13116 |
| abstractText | 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 Abeta 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 Abeta aggregation, the current study examined whether Abeta 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 Abeta plaques in a mouse model of late-onset AD that does not develop Abeta pathology spontaneously. In aged 5XFAD mice infected via eye scarification, high density of Abeta 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 Abeta deposits, however, no association between HSV-1 and Abeta aggregates could be found. To test whether HSV-1 triggers Abeta aggregation in a mouse model that lacks spontaneous Abeta pathology, 13-month-old hAbeta/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 Abeta 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 Abeta pathology. |
