1 Inhibitors of COP - mediated transport and cholera toxin action inhibit SV 40 infection

Simian Virus 40 (SV40) is a non-enveloped virus which has been shown to pass from surface caveolae to the endoplasmic reticulum (ER) in an apparently novel infectious entry pathway. We now show that the initial entry step is blocked by brefeldin A (BFA) and by incubation at 20°C. Subsequent to the entry step, the virus reaches a domain of the rough ER by an unknown pathway. This intracellular trafficking pathway is also BFA-sensitive. Infection is strongly inhibited by expression of GTP-restricted Arf1 and Sar1 mutants and by microinjection of antibodies to βCOP. In addition we demonstrate a potent inhibition of SV40 infection by the dipeptide, Cbz-gly-phe-NH2, which a lso inhibits late events in cholera toxin action. Our results identify novel inhibitors of SV40 infection and show that SV40 requires COPI-and COPII-dependent transport steps for successful infection.