# PROJECT 2: Determine clinically relevant host-viral dependency networks for respiratory infections including SARS-CoV-2

> **NIH NIH U19** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2023 · $672,529

## Abstract

PROJECT 2: DETERMINE CLINICALLY RELEVANT HOST-VIRAL DEPENDENCY NETWORKS FOR
RESPIRATORY INFECTIONS INCLUDING SARS-COV-2
SUMMARY
Respiratory viral infections caused by SARS-CoV-2, influenza A and B viruses, respiratory syncytial virus, and
human parainfluenza virus are a significant public health burden globally. Although vaccines are available for
some of these viruses, the inequality in access and the constant virus evolution diminish their efficacy. Moreover,
effective therapeutics preventing and treating severe respiratory viral diseases are still largely lacking. In Project
2, we will exploit viral dependencies on host factor networks to gain insight into disease mechanisms and develop
new therapeutic approaches. We focus on relevant primary cell models, panviral mechanisms and innovative
reverse genetics technologies. In Aim 1, proteomics and transcriptomics analyses will be performed with the
Technology Core to determine global changes in protein abundance, post-translational modifications, and gene
expression profiles in infected primary human lung cells and three-dimensional human airway organoids. Results
will be integrated by the Data Management and Bioinformatics and Modeling Cores using existing -omics
and human GWAS datasets to search for signatures that correlate with clinical pathogenesis. In Aim 2, virus and
host genetics will be used to uncover host dependency factors critical for respiratory infection, using rapid SARS-
CoV-2 cloning as well as genome-wide CRISPR-screens. In Aim 3, using supernatants of infected cells and
patient serum samples, we will characterize the pro-inflammatory effects of SARS-CoV-2 ORF8 and other
secreted viral proteins in correlation with clinical data. With Project 1, we will test their effect on other respiratory
viruses and Mycobacterium tuberculosis infection. We anticipate that these studies will have a significant impact
on public health measures against respiratory virus infections in the future.

## Key facts

- **NIH application ID:** 10550002
- **Project number:** 2U19AI135990-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Melanie Maria Ott
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $672,529
- **Award type:** 2
- **Project period:** 2018-08-17 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10550002

## Citation

> US National Institutes of Health, RePORTER application 10550002, PROJECT 2: Determine clinically relevant host-viral dependency networks for respiratory infections including SARS-CoV-2 (2U19AI135990-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10550002. Licensed CC0.

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