# Genetic basis for TLR7-independent antiretroviral antibody responses

> **NIH NIH R21** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2024 · $229,650

## Abstract

PROJECT SUMMARY/ABSTRACT
The goal of this application is to identify novel mechanisms by which antiretroviral antibody responses are
generated. Retroviruses are highly successful pathogens, able to subvert or evade immune responses in most
infected individuals. In some unique cases, the detection of viral infection by the innate immune system results
in the induction of an adaptive immune response able to control viral infection and prevent the development of
disease. This ability to control retroviral replication is most often driven by the specific genetic make-up of the
host. However, investigation of the genetic and immunologic basis for these responses in humans is extremely
difficult; therefore, animal models of retroviral infection are required for the dissection of the requirements for
protective immune responses. To this end, murine models of retroviral infection have provided essential insights
into understanding the molecular mechanisms of anti-retroviral immune responses. In particular, inbred strains
capable of mounting neutralizing antibody responses provide the opportunity to dissect the signaling pathways
underlying these responses. The canonical pathway for antiviral antibody production in mice involves detection
of retroviral RNA in the endosome by the innate immune receptor Toll-like receptor 7 (TLR7). TLR7/MyD88
signaling is followed by activation of CD4+ T cells, and IFNγ-mediated stimulation of Ab production by virus-
specific B cells. This is the predominant pathway for the generation of neutralizing responses to a variety of RNA
virus infections, including retroviral infections. We recently identified that some inbred mice inherit an alternative,
TLR7-independent pathway to produce retrovirus-neutralizing antibodies. The studies proposed in this
application will elucidate (1) the genetic mechanisms underlying this unique pathway, and (2) the alternative
innate immune mechanism that stimulates this alternative pathway. The knowledge gained by this investigation
will uncover the basis for a previously unappreciated pathway for antibody production in response to viral
infection. Such insight could greatly aid the development of new animal models of human disease and novel
therapeutic intervention.

## Key facts

- **NIH application ID:** 10884783
- **Project number:** 1R21AI178197-01A1
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Melissa E Kane
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $229,650
- **Award type:** 1
- **Project period:** 2024-05-23 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10884783

## Citation

> US National Institutes of Health, RePORTER application 10884783, Genetic basis for TLR7-independent antiretroviral antibody responses (1R21AI178197-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10884783. Licensed CC0.

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