Inactivation and Inhibition of Replication of the Enveloped Bacteriophage φ6 by Fatty Acids

The enveloped bacteriophage φ6 has been shown to be an interesting model system for the study of chemical agents that might have specific antiviral effects against lipid-containing mammalian viruses. In this report, we describe two types of antiviral activity exhibited by several fatty acids against bacteriophage φ6. Oleic acid (18:1) and palmitoleic acid (16:1) were potent inactivators of the virus. Treatment with either fatty acid at 50 μg/ml at 25 or 0°C for 30 min reduced the virus titer to about 0.1% of the initial titer. Oleic acid at a concentration as low as 3 μg/ml (∼10−2 mM) reduced the virus titer to <1% of the initial titer within 30 min. Ultracentrifugation analyses of14 C-amino acid- and32 P-labeled virus treated with oleic acid indicated that the virion is largely disassembled by the treatment. Myristic acid (14:0) and palmitic acid (16:0) did not inactivate φ6 at 50 μg/ml, but nevertheless did prevent φ6 plaque production. Single-step virus growth experiments in which fatty acid was added at various times before or after infection indicated that it was an early stage of the φ6 replication cycle that was inhibited by the presence of myristic acid and that the inhibition occurred only if the myristic acid concentration in the extracellular growth medium was ≳10 μg/ml. φ6 could attach to its host cell in the presence of myristic acid at 50 μg/ml. We conclude that the fatty acids that prevent φ6 replication probably do so by interfering with the entry of the viral genome into the host cell.