Why is acyclovir largely ineffective against human cytomegalovirus infections?

Acyclovir is primarily effective against herpesviruses, which include herpes simplex virus and varicella-zoster virus, due to its mechanism of action that relies on the viral enzyme thymidine kinase. In the case of human cytomegalovirus (CMV), the virus does not have the same dependency on thymidine kinase as other herpesviruses. CMV utilizes its own unique enzymes for its replication process, which does not involve the same mechanisms that acyclovir targets. Therefore, since CMV lacks the necessary thymidine kinase to convert acyclovir into its active triphosphate form, acyclovir becomes largely ineffective against CMV infections.

This insight into the specific biochemical pathways of CMV highlights why acyclovir cannot inhibit its replication, as it fundamentally relies on the presence of a viral enzyme that is either absent or functionally different in CMV compared to other herpesviruses.