# Mechanistic dissection of the link between virus infection and Alzheimer’s disease in a model organism

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2022 · $398,215

## Abstract

SUMMARY
Lifespan and aging-associated neurodegenerative conditions, such as Alzheimer’s disease, are thought to be
controlled by internal (genetic) and external (environment) factors. We propose that the interactions with
microorganisms are an important environmental factor. Animals are constantly infected by microorganisms, but
whether infection and the associated immune responses affect lifespan and aging-related diseases is poorly
understood. The overall goal of this project is to examine the effect of RNA virus infection on aging and
Alzheimer’s disease in the model organism Drosophila melanogaster. A large body of work supports the idea
that major features and principles of innate immunity and aging are conserved in evolution and Drosophila has
proven to be an excellent system to understand both innate immunity and aging. Our lab has established multiple
models of chronic and acute infection viral in Drosophila. Aging and neurodegeneration in flies are associated
with innate immunity activation, but previous research focused on acute pathogenic or commensal bacteria.
Chronic infections are common in animals, but the effects of continued activation of antiviral responses on
senescence have not been well defined. We propose to define the links among chronic viral infection, innate
immunity, Alzheimer’s disease and provide mechanistic insights into the neurodegenerative process. We will
characterize the acceleration of aging in chronically infected individuals and test its mechanistic underpinnings
and consequences for other aging phenotypes, such as susceptibility to Aß in Alzheimer’s disease. The excellent
models for aging and Alzheimer’s disease in Drosophila will allow us to examine the mecanistic links between
these processes. Our preliminary experiments show that chronic viral infection leads to an accelerated aging of
the transcriptome accompanied by a shortened lifespan. This transcriptome analysis implicated two major
pathways in aging and viral infection: Nonsense-mediated decay (NMD) and the integrated stress response
(ISR). We have organized the proposal into three specific aims: Aim 1 focuses on immunosenescence, a
progressive aging-related decline in the immune system and the effects of chronic RNA virus infection on lifespan
and aging-associated diseases. Aim 2 will determine the links among infection, aging and NMD and ISR
pathways. We expect that these studies will provide critical information on the linkages among infection,
immunity, aging and neurodegeneration.

## Key facts

- **NIH application ID:** 10498080
- **Project number:** 3R01AI137471-05S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Raul Andino
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $398,215
- **Award type:** 3
- **Project period:** 2018-09-14 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10498080

## Citation

> US National Institutes of Health, RePORTER application 10498080, Mechanistic dissection of the link between virus infection and Alzheimer’s disease in a model organism (3R01AI137471-05S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10498080. Licensed CC0.

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