# REGULATION OF IFN ALPHA GENE EXPRESSION

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 1991 · $206,344

## Abstract

The long-term objective of this study is to determine the biological role
of the interferon (IFN) system in viral infection and virus-induced
neoplasia by using mice as a model system; the use of mice provides many
advantages to this study, such as availability of a single genetic
background, mice strains that are genetically restricted in IFN production,
and the possibility of analyzing the expression of IFN and viral genes
during the progression of infection.  In the past and current funding
periods, we cloned and characterized a cluster of IFN genes and studied the
regulation of their expression both in infected cells and in mice.  The
present proposal focuses on:  1) Identification of a virus-mediated signal
transduction pathway that leads to the activation of IFN genes by use of
primary macrophage cultures isolated from mice expressing different
genotypes.  We will examine the relationship between virus-induced 1,2-DG
and PKC-dependent accumulation of IFN mRNA; 2) Detection of factors that
determine the cell- specific expression of IFN-alpha genes in macrophages
and spleen cells.  We will characterize the binding of induction-specific
nuclear proteins to IFN-alpha promoter regions and identify the factors
that are critical for induction of these genes; 3) Determination of factors
that modulate the IFN synthesis in vivo.  We will examine the mechanism by
which the IF-1 locus modulate IFN synthesis and examine the effect of
retroviral infection on the expression of IFN genes; and 4) Purification
and cloning of the F1 protein; we will purify the F1 protein (nuclear
factor we identified to be essential for expression of IFN-alpha4 gene in
L-cells), clone and sequence its cDNA.

We believe that the knowledge of the regulation of IFN gene expression and
its dependence on genetic factors is essential for our understanding of the
IFN system in man, where the deletion (or defect) in IFN genes can be often
found in tumor cells and aberrant expression can be associated both with
predisposition to infection and with an increase in pathogenicity of viral
infections.  In addition, this study will provide a more rational basis for
the possible therapeutic manipulation of the IFN system in man.

## Key facts

- **NIH application ID:** 3129120
- **Project number:** 2R01AI019737-09
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **SAM.gov UEI:** FTMTDMBR29C7
- **Principal Investigator:** Paula M Pitha-Rowe
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $206,344
- **Award type:** 2
- **Project period:** 1983-07-01 → 1996-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3129120

## Citation

> US National Institutes of Health, RePORTER application 3129120, REGULATION OF IFN ALPHA GENE EXPRESSION (2R01AI019737-09). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3129120. Licensed CC0.

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