# REGULATION OF INTERFERON PRODUCTION

> **NIH NIH R01** · ROCKEFELLER UNIVERSITY · 1987 · $190,014

## Abstract

The structure and function of human interferon (IFN) genes in experimental
systems such as poly(I).poly(C)-induced human diploid fibroblasts (FS-4)
and bromodeoxyuridine (BrdUrd)-treated, Sendai virus-induced human
lymphoblastoid cells (Namalwa) continue to command our interest.  We have
succeeded in detecting novel human IFN-alpha and beta mRNAs using
translation assays (e.g., the 1.8 kb IFN-alphaL and the 1.3 kb IFN-beta2
mRNAs); in assigning distinct biologically active IFN-beta mRNA species to
human chromosomes 2, 5 and 9; in isolating several novel IFN-beta-related
human genomic DNA clones (in addition to the classical IFN-beta gene that
resides on chromosome 9); and, in turn, in assigning some of these to human
chromosomes 2 (clone lambdaB3) and 4 (clone lambdaB4) using
blot-hybridization procedures.

I. Human IFN locus on chromosome 2.  Our highest research priority is to
study exhaustively the IFN-beta locus on chromosome 2 (14 kb of nucleotide
sequence data are already available), its transcription products (e.g., the
1.8 kb IFN-beta3 mRNA), the IFN protein(s) derived therefrom and the
conditions necessary for its expression.  DNA at this locus consists of
subdomains highly related to IFN-beta1 and undergoes somatic rearrangement
and amplification.  The possibility that this DNA rearrangement may be a
necessary requirement for the expression of the IFN locus on chromosome 2
is exciting.

II. Human IFN locus on chromosome 9.  The demonstration by us that the
classical IFN-beta1 gene and the alpha1-cross-hybridizing genes (all
located on chromosome 9) are constructed of DNA subunits leads to a series
of structure-activity studies on IFN proteins expressed by genetically
engineered IFN-alpha1 and beta1 "half-genes" (as well as by subdomains of
lambdaB3 DNA).  The molecular details of biologically important apparent
read-through transcription across these genes will also be investigated.
The regulation of the stability of IFN-beta1 mRNA in cell-free systems
derived from FS-4 cells induced with poly(I).poly(C) in the presence and
absence of "superinducing" agents will also be investigated.

III. Other human IFN loci.  We shall also characterize and study several
additional IFN-beta-related human genomic DNA clones that we have already
isolated (e.g. lambdaB4 assigned to chromosome 4) and continue our efforts
to obtain cDNA clones corresponding to human IFN-alphaL and beta2 mRNAs.

The proposed research plan is designed to explore the complex molecular
biology of the human IFN system and is likely to provide a basis for the
production of novel human IFNs that may be useful in the clinic against a
variety of viral and neoplastic diseases.

## Key facts

- **NIH application ID:** 3126621
- **Project number:** 5R01AI016262-09
- **Recipient organization:** ROCKEFELLER UNIVERSITY
- **SAM.gov UEI:** LHGDNJMZ64Y1
- **Principal Investigator:** PRAVIN B SEHGAL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $190,014
- **Award type:** 5
- **Project period:** 1979-09-01 → 1990-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3126621

## Citation

> US National Institutes of Health, RePORTER application 3126621, REGULATION OF INTERFERON PRODUCTION (5R01AI016262-09). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3126621. Licensed CC0.

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