# Novel Approaches to Innate Immunity Against HIV-1 and Other Co-infection Viruses

> **NIH NIH DP1** · UNIVERSITY OF COLORADO DENVER · 2021 · $777,500

## Abstract

Project Summary
Of the two main goals of the HIV-1 field – immune protection of the uninfected, and cure
– cure is more imaginable at present. Certainly a globally applicable sterilizing vaccine
seems far away. There is little optimism that currently available strategies will produce
effective adaptive immune system protection against HIV-1 for uninfected but at-risk
individuals (people with the disease of addiction, people with sexual exposure). This
NIDA Avant Garde project will align with RFA goals by pursuing a solidly innovative
direction that also differs strongly from our previous work. It concerns innate rather than
adaptive immunity, and it is based on our recently published body of data showing that
transgenic expression of a viral RNA-dependent RNA polymerase (RdRP), in the
absence of other viral proteins, and therefore unsequestered in the cell within viral
replication factories, can profoundly reconfigure mammalian innate antiviral immunity. It
dramatically upregulates many antiviral factors, and provides broad-spectrum antiviral
protection to mice. This response is strongly HIV-1-protective in corroborative human
cell models. We hypothesize that it may also have application to the co-infection
pathogens that afflict people with addiction. In the mouse, the radically altered innate
immune system proteome is stable life-long and, surprisingly, does not trigger any
inflammatory pathology. Along with the profound antiviral effects, this latter provocative
and counterintuitive observation has multiple downstream discovery opportunities. Here
we will determine the mechanisms involved and use the discoveries to formulate new
strategies to achieve protection against HIV-1 in at-risk populations.

## Key facts

- **NIH application ID:** 10114260
- **Project number:** 5DP1DA043915-05
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Eric M. Poeschla
- **Activity code:** DP1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $777,500
- **Award type:** 5
- **Project period:** 2017-04-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10114260

## Citation

> US National Institutes of Health, RePORTER application 10114260, Novel Approaches to Innate Immunity Against HIV-1 and Other Co-infection Viruses (5DP1DA043915-05). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10114260. Licensed CC0.

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