Nucleoside pools of acyclovir-treated herpes simplex type 1 infected cells

Area of Science:

• Virology
• Cell Biology
• Pharmacology

Background:

• Nucleoside pools are crucial for cellular processes and viral replication.
• Herpes simplex virus type 1 (HSV-1) manipulates host cell metabolism.
• Antiviral drugs like acyclovir (ACV) target viral enzymes.

Purpose of the Study:

• To analyze nucleoside pools in HSV-1 infected and uninfected cells.
• To investigate the impact of deoxythymidine (dThd) on antiviral drug efficacy.
• To understand the mechanism of acyclovir resistance in different cell types.

Main Methods:

• High-performance liquid chromatography (HPLC) for nucleoside analysis.
• Infection of African green monkey kidney (GMK) cells and human fetal lung fibroblasts (HL) with HSV-1.
• Treatment with antiviral drugs: acyclovir (ACV) and phosphonoformic acid (PFA).

Main Results:

• Deoxythymidine (dThd) and adenosine (Ado) were the primary measurable nucleosides.
• GMK cells had higher dThd pools than HL cells; HSV-1 infection reduced GMK cell dThd.
• ACV inhibited HSV-1 replication, restoring dThd levels; added dThd reduced ACV efficacy but not PFA efficacy.

Conclusions:

• High endogenous dThd levels in GMK cells may explain lower ACV antiviral activity.
• ACV efficacy is dependent on HSV-induced deoxythymidine kinase (dTK) and dThd availability.
• PFA's dTK-independent mechanism offers an alternative antiviral strategy.