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Inhibition of the development of Lee influenza virus by puromycin

ScholarsArchive at Oregon State University

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Title Inhibition of the development of Lee influenza virus by puromycin
Names Hobbs, Joe Nelson (creator)
Pilcher, K. S. (advisor)
Date Issued 1964-02-04 (iso8601)
Note Graduation date: 1964
Abstract The development of the Lee strain of type B influenza
virus was shown to be inhibited by puromycin in tissue culture of the chick embryo chorioallantoic membrane. The
compound is an antibiotic of unique structure which has
been reported to possess a broad range of biological activity
against unicellular and multicellular organisms. Investigations were carried out to examine the extent of
inhibition induced by puromycin and to discover possible
explanations for its antiviral activity.
Puromycin caused complete inhibition of Lee influenza
virus development in tissue cultures at a concentration of
8.0 micrograms per ml, marked inhibition at 4.0 micrograms
per ml, and significant inhibition at 2.0 micrograms per
ml. The compound inhibited the formation of infectious
virus in tissue cultures, as well as virus hemagglutinin. At a concentration of 4.0 micrograms per ml it caused inhibition
of cell growth, but did not block all metabolic
activity. In vitro experiments indicated that the compound
was not virucidal and did not influence the end point of
the hemagglutination reaction. At a concentration of 4.0
micrograms per ml it did not interfere with the adsorption
of virus to the chorioallantoic membrane in vitro. The
combination of L-canavanine plus puromycin showed a synergistic
effect on the inhlbition of virus development in
tissue cultures. Combinations of ribonuclease plus puromycin,
benzimidazole plus puromycin and m-tyrosine plus
puromycin showed additive effects on virus inhibition in
tissue cultures.
None of a group of purines, pyrimidines or their nucleosides
or nucleotides was able to reverse the inhibition
caused by puromycin in tissue cultures. A dose of 1.0 mg
of the compound administered twice daily for three days
did not interfere with the development of influenza virus
in mouse lung.
The amino nucleoside of puromycin not only failed to
inhibit the virus but actually gave a significant enhancement
of virus yield in tissue culture fluids at a concentration
of 0.20 mg/ml. Concentrations of 0.40 mg and
0.10 mg per ml caused a significant increase of the virus concentration in the culture fluid. This proved that the
amino acid moiety of the molecule is necessary for the inhibition
of influenza virus.
It appears from the results obtained that the inhibition
of virus development induced by puromycin may be due to its
interference with normal synthesis or utilization of metabolites
essential for the multiplication of the host cell
and of the virus, possibly the synthesis of protein.
Genre Thesis/Dissertation
Topic Puromycin
Identifier http://hdl.handle.net/1957/48454

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