What enzyme activates ganciclovir?
Herpes simplex virus type 1 thymidine kinase (HSV-TK) activates ganciclovir which was found to be 3 orders of magnitude more efficient than any human kinase.
What does thymidine kinase do?
Thymidine kinase (TK) activity is measured by radioenzymatic assay. TK is an enzyme that catalyses the phosphorylation of deoxythymidine to deoxythymidine monophosphate. Its activity is highest in G1-S translation checkpoint and then declines rapidly in the G2 phase of the cell cycle.
What is HSV TK gene?
– herpes simplex virus thymidine kinase (HSV-TK) gene. herpes simplex virus thymidine kinase (HSV-TK) gene. In the cell transduced with this gene, an expressed HSV-TK gene has effect on ganciclovir which is generally used as an anti-virus drug, and changes it to a toxic agent. So it induces the cell death (suicide).
How is ganciclovir activated?
Mechanism of action. Ganciclovir is a synthetic analogue of 2′-deoxy-guanosine. It is first phosphorylated to ganciclovir monophosphate by a viral kinase encoded by the cytomegalovirus (CMV) gene UL97 during infection.
How do you give ganciclovir?
Caution: Ganciclovir must be administered by intravenous infusion over 1 hour at a concentration not exceeding 10 mg/mL. Do not administer by rapid or bolus intravenous injection because the resulting excessive plasma levels may increase the toxicity of ganciclovir.
What are TK levels?
Objective: Serum thymidine kinase (TK) levels have been shown to be correlated with survival in many malignancies, including chronic lymphocytic leukaemia (CLL). This study was designed to investigate associations between TK levels and other prognostic markers, in newly and previously diagnosed Binet stage A patients.
Does CMV have thymidine kinase?
The major difference is that CMV does not contain a thymidine kinase. Protein UL97 phosphorylates ganciclovir to ganciclovir monophosphate. One of the mechanisms of ganciclovir resistance is a change in UL97.
How does HSV TK work?
HSV-1 is mainly transmitted by oral-to-oral contact to cause oral herpes infection, via contact with the HSV-1 virus in sores, saliva, and surfaces in or around the mouth. However, HSV-1 can also be transmitted to the genital area through oral-genital contact to cause genital herpes.
What enzyme does acyclovir inhibit?
Acyclovir triphosphate competitively inhibits viral DNA polymerase by acting as an analog to deoxyguanosine triphosphate (dGTP).
What is the use of ganciclovir?
Ganciclovir capsules are used to treat cytomegalovirus (CMV) retinitis (eye infection that can cause blindness) in people whose immune system is not working normally. Ganciclovir capsules are used to treat CMV retinitis after the condition has been controlled by intravenous (injected into a vein) ganciclovir.
What is the brand name for ganciclovir?
Cytovene (ganciclovir) is an antiviral drug used to treat and prevent infections caused by cytomegalovirus.
What are the side effects of ganciclovir?
Ganciclovir may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:
- nausea.
- vomiting.
- diarrhea.
- constipation.
- stomach pain.
- belching.
- loss of appetite.
- changes in ability to taste food.
What kind of prodrug is ganciclovir for HSV TK?
Ganciclovir (GCV) is a guanosine analog used as a prodrug to obtain a suicide effect in cells transfected with the herpes virus thymidine kinase gene (HSV-tk).
How is GCV used to treat HSV1 TK?
Specifically, GCV is used to exert selective pressure on cells transfected with the “cell suicide gene” HSV1-tk. Normally, eukaryotic cells can survive in the presence of the non-toxic prodrug GCV.
Which is negative selection marker for HSV1 TK?
Ganciclovir (GCV), a guanosine analog, is commonly used in molecular biology together with the negative selection marker herpes virus simplex 1 thymidine kinase (HSV1-TK) gene [1].
How is HSV1 TK converted to GCV monophosphate?
However, upon expression of HSV1-tk, GCV is converted to GCV-monophosphate by HSV1-TK and further phosphorylated to the diphosphate and triphosphate forms by host kinases. GCV-triphosphate, a lethal toxin, is incorporated into the DNA of replicating eukaryotic cells causing premature DNA chain termination and apoptosis [5].