# MECHANISMS OF INTERFERON ACTION

> **NIH NIH R01** · STATE UNIVERSITY OF NEW YORK AT ALBANY · 1987 · $162,461

## Abstract

The long-term objective of this application is an understanding of
the mechanism of action of interferons (IFN).  Three main lines of
research are proposed.  One line of work will examine the
antiviral activity of proteins coded for by IFN-induced mRNAs of
unknown function.  The cDNAs corresponding to several IFN-
induced mRNAs have recently been cloned.  These cDNAs will be
inserted into a shuttle expression vector in an antisense
orientation, in order to produce anti-mRNA which can specifically
anneal with mRNA and suppress its expression.   A vector
containing elements of the BK virus and a neomycin gene under
control of an SV-40 promoter has been constructed and used to
test this method of suppressing the expression of an IFN-induced
mRNA.  Human cells transfected with DNA of the vector
containing 2-5A synthetase cDNA under the control of the VP
promoter, show very low levels of this enzymatic activity after
treatment with IFN.  These cells lack resistance to EMCV
infection.  Other cDNAs will be inserted into separate vectors and
the resistance to infection by different viruses will be tested in
cells transfected with vector DNA.  If resistance to a specific
virus is decreased in cells incapable of producing an IFN-induced
mRNA it will be concluded that the corresponding protein plays
some role in the antiviral mechanisms which affords protection
against that virus.  Another line of research will characterize 2-
5A metabolites, which are inhibitory for the endonuclease (RNase
L) activated by 2-5A.  These compounds have been detected in
IFN-treated cells incubated with poly(I:C) and in cell extracts
incubated either with this dsRNA or with synthetic 2-5A.  The
RNase L inhibitors may play an important role in preventing
indiscriminate RNA cleavage in IFN-treated virus-infected cells.
The inhibitors will be fractionated by HPLC and characterized by
a combination of enzymatic degradations and chemical analysis.
Finally, a third line of research will examine the effect of IFN
administered together with surfactants on the nasal mucosa.
Preliminary experiments have shown that few IFN receptors are
present on this mucosa.  However, membranes prepared from
nasal mucosa have abundant receptors, presumably accessible to
circulating IFN.  Some surfactant agents promote passage of
insulin across the nasal mucosa and their effect on IFN transport
will be assayed by measuring 2-5A synthetase activity in the
mucosal layer of turbinates.  These experiments will be carried
out in the sheep, as an animal model in the IFN prophylaxis
against the common cold.

## Key facts

- **NIH application ID:** 3126544
- **Project number:** 2R01AI016076-07
- **Recipient organization:** STATE UNIVERSITY OF NEW YORK AT ALBANY
- **SAM.gov UEI:** NHH3T1Z96H29
- **Principal Investigator:** Corrado Baglioni
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $162,461
- **Award type:** 2
- **Project period:** 1979-09-01 → 1990-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3126544

## Citation

> US National Institutes of Health, RePORTER application 3126544, MECHANISMS OF INTERFERON ACTION (2R01AI016076-07). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3126544. Licensed CC0.

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