Amino acid substitutions in the thymidine kinase gene of induced acyclovir-resistant herpes simplex virus type 1

Research output: Chapter in Book/Report/Conference proceedingConference contribution

1 Citation (Scopus)

Abstract

Acyclovir (ACV) is an antiviral drug of choice in healthcare setting to treat infections caused by herpes viruses, including, but not limited to genital herpes, cold sores, shingles and chicken pox. Acyclovir resistance has emerged significantly due to extensive use and misuse of this antiviral in human, especially in immunocompromised patients. However, it remains unclear about the amino acid substitutions in thymidine (TK) gene, which specifically confer the resistance-associated mutation in herpes simplex virus. Hence, acyclovir-resistant HSV-1 was selected at high concentration (2.0-4.5 μg/mL), and the TK-gene was subjected to sequencing and genotypic characterization. Genotypic sequences comparison was done using HSV-1 17 (GenBank Accesion no. X14112) for resistance-associated mutation determination whereas HSV-1 KOS, HSV-1 473/08 and HSV clinical isolates sequences were used for polymorphismassociated mutation. The result showed that amino acid substitutions at the non-conserved region (UKM-1: Gln34Lys, UKM-2: Arg32Ser & UKM-5: Arg32Cys) and ATP-binding site (UKM-3: Tyr53End & UKM-4: Ile54Leu) of the TKgene. These discoveries play an important role to extend another dimension to the evolution of acyclovir-resistant HSV-1 and suggest that selection at high ACV concentration induced ACV-resistant HSV-1 evolution. These findings also expand the knowledge on the type of mutations among acyclovir-resistant HSV-1. In conclusion, HSV-1 showed multiple strategies to exhibit acyclovir resistance, including amino acid substitutions in the TK gene.

Original languageEnglish
Title of host publicationAIP Conference Proceedings
Pages254-257
Number of pages4
Volume1571
DOIs
Publication statusPublished - 2013
Event2013 UKM Faculty of Science and Technology Post-Graduate Colloquium - Selangor
Duration: 3 Jul 20134 Jul 2013

Other

Other2013 UKM Faculty of Science and Technology Post-Graduate Colloquium
CitySelangor
Period3/7/134/7/13

Fingerprint

thymidine
viruses
mutations
genes
amino acids
substitutes
chickens
sequencing
adenosine triphosphate
infectious diseases
drugs

Keywords

  • Acyclovir resistance
  • Herpes simplex virus type 1
  • Thymidine kinase gene

ASJC Scopus subject areas

  • Physics and Astronomy(all)

Cite this

Amino acid substitutions in the thymidine kinase gene of induced acyclovir-resistant herpes simplex virus type 1. / Hussin, Ainulkhir; Md Nor, Norefrina Shafinaz; Ibrahim, Nazlina.

AIP Conference Proceedings. Vol. 1571 2013. p. 254-257.

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Hussin, A, Md Nor, NS & Ibrahim, N 2013, Amino acid substitutions in the thymidine kinase gene of induced acyclovir-resistant herpes simplex virus type 1. in AIP Conference Proceedings. vol. 1571, pp. 254-257, 2013 UKM Faculty of Science and Technology Post-Graduate Colloquium, Selangor, 3/7/13. https://doi.org/10.1063/1.4858664
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AB - Acyclovir (ACV) is an antiviral drug of choice in healthcare setting to treat infections caused by herpes viruses, including, but not limited to genital herpes, cold sores, shingles and chicken pox. Acyclovir resistance has emerged significantly due to extensive use and misuse of this antiviral in human, especially in immunocompromised patients. However, it remains unclear about the amino acid substitutions in thymidine (TK) gene, which specifically confer the resistance-associated mutation in herpes simplex virus. Hence, acyclovir-resistant HSV-1 was selected at high concentration (2.0-4.5 μg/mL), and the TK-gene was subjected to sequencing and genotypic characterization. Genotypic sequences comparison was done using HSV-1 17 (GenBank Accesion no. X14112) for resistance-associated mutation determination whereas HSV-1 KOS, HSV-1 473/08 and HSV clinical isolates sequences were used for polymorphismassociated mutation. The result showed that amino acid substitutions at the non-conserved region (UKM-1: Gln34Lys, UKM-2: Arg32Ser & UKM-5: Arg32Cys) and ATP-binding site (UKM-3: Tyr53End & UKM-4: Ile54Leu) of the TKgene. These discoveries play an important role to extend another dimension to the evolution of acyclovir-resistant HSV-1 and suggest that selection at high ACV concentration induced ACV-resistant HSV-1 evolution. These findings also expand the knowledge on the type of mutations among acyclovir-resistant HSV-1. In conclusion, HSV-1 showed multiple strategies to exhibit acyclovir resistance, including amino acid substitutions in the TK gene.

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