# MECHANISM OF INTERFERON ACTION

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA SANTA BARBARA · 1988 · $176,625

## Abstract

The overall objective of the proposed research is to elucidate in molecular
terms the mechanisms by which purified natural and cloned human leukocyte
(IFN-Alpha) and immune (IFN-Gamma) interferons act to affect a wide variety
of fundamental viral and cellular processes.  The specific aims are as
follows:

(1) To elucidate the molecular basis of the differential antiviral effects
of human IFN-Alpha and IFN-Gamma on the replication of reovirus as compared
to vesicular stomatitis virus in human amnion and human fibroblast cells.
Natural and cloned IFN-Alpha subspecies inhibit VSV but not reovirus
replication in human amnion and fibroblast cells; however, cloned IFN-Gamma
inhibits both VSV and reovirus in the human cells.  The antiviral actions
of IFN-Alpha and IFN-Gamma are synergistic for VSV, but not for reovirus.

(2) To construct recombinant DNAs between the dsDNA copies of reovirus S1
and S4 genes and simian virus 40, and to study the effect of IFN on the
expression of SV40-reovirus(S1,S4) recombinant DNAs in transfected monkey
cells as an approach to elucidating the molecular basis of the sensitivity
of reovirus mRNA translation to IFN and the resistance of SV40 mRNA
translation to IFN.  To construct additional SV40-VSV(G protein)
recombinant DNAs, and to study the effect of IFN on their expression as
compared to that of SV40-reovirus (S1,S4) recombinants.  The translation of
SV40 mRNA is not inhibited but the translation of reovirus mRNA is
inhibited in IFN-treated monkey cells doubly infected with SV40 and
reovirus; the translation of SV40 early RNA is also not inhibited in
IFN-treated SV3T3 cells although the replication of both reovirus and VSV
are inhibited.  The synthesis of VSV G protein in COS cells transfected
with an SV40-VSV(G) expression vector is inhibited by IFN.

(3) To continue our efforts to determine the biochemical basis, both in
vitro and in vivo, of the difference in translational efficiency of the
s-class mRNAs of reovirus.  The rate of synthesis of polypeptides Sigma1
and Sigma3 differs by more than 10-fold under conditions where the molar
amount of their mRNAs differ by less than 2-fold.

The health relatedness of the proposed research stems from the likelihood
that the work may contribute to a better understanding of regulatory
mechanisms possibly operative in normal cells as well as virus-infected
cells, and that the elucidation of the molecular mechanisms of action of
the different types of interferons is of immediate importance in view of
the potential applications of IFN in the clinic.

## Key facts

- **NIH application ID:** 3125208
- **Project number:** 5R01AI012520-14
- **Recipient organization:** UNIVERSITY OF CALIFORNIA SANTA BARBARA
- **SAM.gov UEI:** G9QBQDH39DF4
- **Principal Investigator:** Charles E Samuel
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $176,625
- **Award type:** 5
- **Project period:** 1978-05-01 → 1989-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3125208

## Citation

> US National Institutes of Health, RePORTER application 3125208, MECHANISM OF INTERFERON ACTION (5R01AI012520-14). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3125208. Licensed CC0.

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