Effect of Apolipoprotein E on the Cerebral Load of Latent Herpes Simplex Virus Type 1 DNA

  1. Burgos, Javier S. 1
  2. Ramirez, Carlos 1
  3. Sastre, Isabel 1
  4. Valdivieso, Fernando 1
  1. 1 Centro de Biología Molecular Severo Ochoa
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    Centro de Biología Molecular Severo Ochoa

    Madrid, España

    ROR https://ror.org/03v9e8t09

Revista:
Journal of Virology

ISSN: 0022-538X,  1098-5514

Año de publicación: 2006

Volumen: 80

Número: 11

Páginas: 5383-5387

Tipo: Artículo

DOI: 10.1128/JVI.00006-06 GOOGLE SCHOLAR lock_openAcceso abierto editor

Otras publicaciones en: Journal of Virology

Resumen

Herpes simplex virus type 1 (HSV-1) is neurotropic and enters a latent state lasting the lifetime of the host. This pathogen has recently been proposed as a risk factor for Alzheimer's disease (AD) in conjunction with apolipoprotein E4 (ApoE4). In a murine acute infection model, we showed that viral neuroinvasiveness depends directly on the overall ApoE dosage and especially on the presence of isoform ApoE4. If an interaction between ApoE and HSV-1 is involved in AD, it may occur during latency rather than during acute infection. Certainly, ApoE plays an important role in late-onset AD, i.e., at a time in life when the majority of people harbor HSV-1 in their nervous system. In the present work, wild-type, APOE knockout, APOE3, and APOE4 transgenic mice were used to analyze the influence of the ApoE profile on the levels of latent virus DNA. The knockout mice had significantly lower concentrations of the virus in the nervous system than the wild-type mice, while the APOE4 mice had very high levels in the brain compared to the APOE3 animals. ApoE4 seems to facilitate HSV-1 latency in the brain much more so than ApoE3. The APOE dosage correlated directly with the HSV-1 DNA concentration in the brain, strengthening the hypothesis that HSV-1, together with ApoE, might be involved in AD.

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Información de financiación

This work was supported by a grant from the Obra Social Caja Madrid to the Asociación de Familiares de Enfermos de Alzheimer and by an institutional grant from the Fundación Areces to the Centro de Biología Molecular Severo Ochoa. We thank F. Mayor for his continuous encouragement and help and L. Carrasco for providing the HSV-1 KOS strain.

Financiadores

  • Obra Social Caja Madrid Spain
  • Fundación Areces Spain

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