Early Alteration of Poliovirus in Infected Cells and Its Specific Inhibition

TLDR

HeLa cells infected with radioactive poliovirus type 2 were disrupted by ultrasonic treatment and non‑ionic detergent, a method analogous to glutathione‑mediated blockade of cell‑mediated eclipse. Two distinct poliovirus particles were identified: a membrane‑associated complex that releases infectious virus upon SDS treatment and a non‑infectious form that dominates the eclipse phase; the substituted thiopyrimidine S‑7 specifically blocks infection by preventing formation of the infectious complex and also stabilizes the virus against heat inactivation.

Abstract

SUMMARY HeLa cells infected with radioactive poliovirus type 2 were disrupted with ultrasonic treatment, followed by addition of a non-ionic detergent. Two types of virus particles were found to sediment at 80 to 90% the rate of native virus. The first of these appeared to be a complex of native virus particles and membrane components, since treatment with 0.2% SDS released infectious native particles. The second was non-infectious and its sedimentation rate was not greatly altered by SDS. One hour after infection this non-infectious particle was the major product of cell-mediated eclipse. We have confirmed that 10 to 30 μg/ml S-7, a substituted thiopyrimidine, blocks infection of cells by poliovirus in a specific manner. Analysis of cells infected with radioactive poliovirus type 2 in the presence of S-7 showed that the virus particles remained as the complex which can be disrupted with SDS. In addition to blocking cell-mediated eclipse, S-7 stabilizes poliovirus against heat inactivation in vitro at the same concentrations which block infection. This action resembles the effect of 10−2 M-glutathione, which is also known to block cell-mediated eclipse of poliovirus.