# Enhancing Innate Anti-Viral Resistance Through A Community-Based Intervention

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2024 · $633,875

## Abstract

Project Summary
The SARS-CoV-2/COVID-19 pandemic has disproportionately impacted older socioeconomically
disadvantaged African-Americans. This research will test whether a recently developed community-based
intervention program known as Generation Exchange (GenX) can enhance a key biological mediator of
antiviral resistance (Type I interferon response) in this disadvantaged population. Our previous research
has identified a stress-triggered genomic program known as the “Conserved Transcriptional Response to
Adversity” (CTRA). The CTRA is activated by fight-or-flight stress responses and causes immune cells to
reduce antiviral activity and stimulate inflammation, both of which are detrimental in the context of COVID-
19. Our previous research on biological resilience in the face of adversity has also found that the CTRA is
reduced in people with high levels of eudaimonic well-being, which includes purpose in life, generativity,
and pro-social engagement. In the present study, we will conduct a randomized controlled intervention
trial (n=160) to test whether a eudaimonia-promoting intergenerational mentoring program known as
Generation Xchange (GenX) can enhance Type I interferon responses and reduce hyper-inflammatory
responses in older African-American women and men living in a socioeconomically disadvantaged urban
community. Our hypotheses are that GenX will, 1) increase Type I interferon antiviral responses, 2)
reduce hyper-inflammatory bias, and 3) reduce rates of clinical respiratory virus infection and symptomatic
disease (COVID, influenzas, and colds). To identify the biological mechanisms of antiviral resistance in
this specific population, we will also analyze specific antiviral cell types (e.g., plasmacytoid dendritic cells,
monocytes) and gene regulatory processes (e.g., transcription factor activity and single-cell gene
expression). These measures will be used to determine 4) which biological factors are most important in
protecting older African-Americans from respiratory virus infection, 5) how those biological risk factors are
linked to other established respiratory virus risk factors (e.g., overweight/obesity, pre-existing chronic
disease, low physical activity, poor sleep, social isolation/loneliness), and 6) which biological factors are
impacted by GenX. Finally, we test the hypothesis that 7) GenX will show positive effects for both women
and men, for those with low or high education level, and for those with low or high levels of background
risk factors (e.g., overweight/obesity, chronic disease, low physical activity, social isolation/loneliness).
Our overarching goal is to establish a community-based biobehavioral intervention program that is broadly
scalable, involves defined biological mechanisms of antiviral resistance, and leverages social support and
eudaimonic well-being to mitigate the detrimental effects of age and social disadvantage on host
resistance to respiratory virus infection among COVID-vulnerable older Afric...

## Key facts

- **NIH application ID:** 10867263
- **Project number:** 5R01AG073053-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** STEVE W COLE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $633,875
- **Award type:** 5
- **Project period:** 2022-03-15 → 2028-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10867263

## Citation

> US National Institutes of Health, RePORTER application 10867263, Enhancing Innate Anti-Viral Resistance Through A Community-Based Intervention (5R01AG073053-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10867263. Licensed CC0.

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