# Transcriptomics-based identification of cell type specific host genes and gene networks perturbed by HSV-1 in cerebral organoids.

> **NIH NIH R01** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 2024 · $837,492

## Abstract

PROJECT SUMMARY/ABSTRACT
 Herpesviruses such as herpes simplex virus 1 (HSV-1) had been associated with increased risk for
Alzheimer’s Disease (AD) through several seminal clinical, molecular and epidemiological studies. Building on
top of the foundation established by these research, two seminal papers reported in Neuron 2018 that
molecular gene networks implicating herpesviruses, such as HHV-6A, HHV-7 and HSV-1, were enriched in
preclinical AD brains. Furthermore, it was shown that HSV-1 infection led to amyloidosis of Amyloid beta (Aβ).
 Since then, our team has been creating and developing novel resources, technologies and collaborations, to
systematically address the role of pathogens (e.g. HSV-1) in AD and AD-related dementias. More specifically,
we used recent human in-vitro induced pluripotent stem cell (iPSC) based models (e.g. cerebral organoids,
cOrgs), combined with large-scale omics data from human samples (post-mortem brains and CSF antigen
profiling) to identify transcriptomic perturbations by HSV-1 and their association with AD-associated genes.
Given the importance of precision medicine, we will also like to understand if AD-associated host genetics (e.g.
APOE e4) play a role to exacerbate the cell type specific transcriptomic perturbations by HSV-1 in cOrgs.
 Using recent spatial single-cell RNA sequencing (scRNA-seq) technologies and methods in Aims 1-2, we
will also like to directly evaluate if there are cell types in cOrgs and post-mortem brains targeted by HSV-1 and
other herpesviruses or cell type co-localization differences and cell type specific gene networks that are critical
for AD subtype and outcome analyses. We aim to understand if AD-associated host genetics might play a role
to exacerbate these cell type specific perturbations by HSV-1 in cOrgs and the effects of acyclovir (ACV)
treatment in reversing AD-associated cell type specific gene networks and pathways.
 We have also established high-throughput, scalable and quantitative non-transcriptomics based assays
(ELISA and flow cytometry) to quantify AD-associated readouts (secreted Ab42/40/38 and intracellular Ab42
and phosphorylated Tau-Thr212) to validate our results from the transcriptomics based approaches in Aim 3.
These AD-associated readouts, coupled with the use of flow cytometry results from cell type specific antibody
markers, will enable us to dissect the contribution of cell types to AD and illuminate molecular mechanisms on
how herpesviruses can contribute to AD pathogenesis or disease progression.
 Finally, in Aim 4, we propose to perform data integration of the multi-transcriptomics datasets from human
cOrgs and post-mortem brains with flow cytometry data, as well as previously published large-scale datasets
from post-mortem brains of AD patients, to estimate the population prevalence of AD patient subtypes whose
etiology may be triggered by herpesviral infections and who may benefit from early anti-herpetic treatment.
Our research has broad implicat...

## Key facts

- **NIH application ID:** 10885290
- **Project number:** 1R01AG083881-01A1
- **Recipient organization:** UNIV OF MASSACHUSETTS MED SCH WORCESTER
- **Principal Investigator:** Teng-Ting Elaine Lim
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $837,492
- **Award type:** 1
- **Project period:** 2024-07-15 → 2029-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10885290

## Citation

> US National Institutes of Health, RePORTER application 10885290, Transcriptomics-based identification of cell type specific host genes and gene networks perturbed by HSV-1 in cerebral organoids. (1R01AG083881-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10885290. Licensed CC0.

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