# Genetic basis for interferon-gamma-independent antiviral antibody production

> **NIH NIH R03** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2024 · $70,650

## Abstract

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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. 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 stimulation of antigen-
specific B cells by the cytokine interferon-γ (IFNγ), resulting in production of virus specific antibodies of the IgG2a
isotype. This is the predominant pathway for the generation of neutralizing responses to a variety of viral
infections, including retroviral infections. We recently identified that some inbred mice inherit an alternative, IFNγ-
independent pathway to produce retrovirus-neutralizing IgG2a antibodies. The mechanism of resistance is
recessive and controlled by a single locus in which we have identified a candidate gene. The studies proposed
in this application will elucidate the genetic mechanisms underlying this unique 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:** 10984780
- **Project number:** 1R03AI180680-01A1
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Melissa E Kane
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $70,650
- **Award type:** 1
- **Project period:** 2024-05-10 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10984780

## Citation

> US National Institutes of Health, RePORTER application 10984780, Genetic basis for interferon-gamma-independent antiviral antibody production (1R03AI180680-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10984780. Licensed CC0.

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