Inhibition of Sindbis Virus Production by Media of Low Ionic Strength: Intracellular Events and Requirements for Reversal

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Abstract
Incubation of Sindbis virus-infected cultures in medium with an ionic strength of 0.105 reduced the virus yield more than 99%. This inhibition was rapidly reversed by exposing the cultures to normal medium: within 20 min the previously inhibited cultures had released as much infectious virus as normal controls had produced during hours of incubation. The following intracellular processes were essentially normal in inhibited, infected monolayers: protein and phospholipid synthesis, the synthesis of infectious viral ribonucleic acid and its incorporation into nucleocapsids, and viral modification of the cell membrane. Accelerated virus production was detected within 20 sec after exposure of inhibited cultures to normal medium. It required an ionic strength greater than 0.145, a p H above 6.7, and a temperature above 21 C. It was not dependent on osmotic pressure, de novo protein synthesis, or a functional energy metabolism. Virus release also occurred in sonic-treated materials of inhibited cells under the same conditions as in living cells. Potential applications of the inhibition to concentration of virus stocks or to obtaining virus in nonphysiological solutions are noted. Preliminary studies with Semiliki Forest virus, Newcastle disease virus, and vesicular stomatitis virus suggest that this phenomenon may be limited to arboviruses.