Mechanism of action of 9-(1,3-Dihydroxy-2-propoxymethyl) guanine for its Anti-herpes Activity : Inhibition of Viral DNA and Protein Synthesis in Cells Infected with Herpes Simplex Virus Herpes Simplex Virus로 감염시킨 세포에서의 바이러스의 DNA와 단백합성의 억제작용 = 9-(1,3-Dihydroxy-2-propoxymethyl)guanine의 항바이러스 효과에 대한 작용기 전

국문 초록 (Abstract)

본 실험에서는 항바이러스 약물인 9-(1,3-dihydroxy-2-propoxymethy) guarine(DHPG)의 항바이러스 효과의 작용기전을 추구하기 위하여 herpes simplex virus(type Ⅰ)가 증식하는 세포에서 바이러스의 DNA와 단백합성에 대한 DHPG의 효과를 실험하였다.
1) DHPG 1 μM농도에서는 선택적으로 바이러스의 DNA합성이 억제되었다. 그러나 그 이상의 고농도에서는 세포의 DNA합성도 억제되었다.
2) DHPG 5, 10, 20 및 50 μM농도에서 만기에 바이러스의 β-protein의 합성이 증가되었다. 그러나 γ-protein의 합성은 DHPG 투여량 증가에 따라서 현저히 억제되었다.
즉 DHPG는 일차적으로 바이러스의 DNA 합성을 억제하고 DNA 합성억제로 인하여 γ-protein 합성이 감소되는 것으로 생각되며, 바이러스의 γ-protein합성의 감소가 DHPG의 항바이러스 작용에 어떤 역할을 할 것이라고 사료된다.

다국어 초록 (Multilingual Abstract)

In the present study we examined the effect of antiviral agent 9-(1,3-dihydroxy-2-propoxymethyl) guanine(DHPG) on herpes simplex virus type 1(HSV-1) DNA and protein synthesis during virus replication to understand its mechanism of antiherpetic action DHPG, in a concentration of 1 μM, markedly and selectively inhibited the synthesis of viral DNA in HSV-1 infected cells, but in higher concentration also suppressed the synthesis of cellular DNA. Treatment of virus infected cells with DHPG significantly increased thc synthesis of beta proteins in the later stage of viral infection. However, DHPG notably or completely diminished the level of gamma proteins, and did so in a dose dependent fashion. The increase in the expression of beta gene products was most likely a response to the inhibition of gamma proteins synthesis by DHPG. The reduction of the synthesis of gamma proteins by DHPG may due to the inhibition of progeny viral DNA synthesis. We conclude that DHPG primarily inhibits the synthesis of viral DNA. and by doing so exhibits its antiherpetic activity. The alteration in viral proteins synthesis in the presence of DHPG might result from the alteration in viral DNA synthesis