Effect of 2′,5′-Oligoadenylate on Herpes Simplex Virus-Infected Cells and Preventive Action of 2′,5′-Oligoadenylate on the Lethal Effect of HSV-2

Abstract

Antiviral effects of ppp(A2'p)nA, (2-5A) on herpes simplex virus type 1 or type 2 (HSV-1 or HSV-2)-infected baby hamster kidney fibroblasts (BHK cells) and HSV-2-infected female guinea pigs were examined. 2-5A was introduced into BHK cells in the form of a calcium phosphate precipitate and as an ointment of polyethylene glycol (PEG) into guinea pig vagina. Under optimum conditions, 2-5A trimer and other 2-5A derivatives inhibited over 90% of HSV-1 syncytia formation and over 50% of HSV-2 plaque formation. The growth of uninfected cells was only slightly and transiently inhibited under these conditions. Northern analysis of viral immediate early mRNAs and cellular mRNAs showed that all transcripts determined were reduced in amount by the 2-5A trimer treatment. The reduction in level of viral mRNAs (ICP4, ICP22, and ICP47) by 2-5A trimer was significantly more than that of cellular mRNAs (represented by beta-actin). HSV-2 (strain 186) inoculation into the vagina of female guinea pigs causes severe symptoms in the genital area and high mortality. Topically applied 2-5A trimer almost completely prevented the lethal effect of HSV-2. These data are discussed from the viewpoint of mechanism of interferon action.