Importance of C-terminus of herpes simplex virus type 1 thymidine kinase for maintaining thymidine kinase and acyclovir-phosphorylation activities

✍ Scribed by Masayuki Saijo; Tatsuo Suzutani; Masahiro Niikura; Shigeru Morikawa; Ichiro Kurane

• Publisher: John Wiley and Sons
• Year: 2002
• Tongue: English
• Weight: 127 KB
• Volume: 66
• Category: Article
• ISSN: 0146-6615
• DOI: 10.1002/jmv.2157

✦ Synopsis

Abstract

We previously isolated an acyclovir (ACV)‐resistant herpes simplex virus type 1 (HSV‐1), strain TAR, from a child with Wiskott‐Aldrich syndrome. An acyclovir‐sensitive HSV‐1, strain TAS, had been isolated from the same patient before the isolation of HSV‐1 TAR. The TK protein of ACV‐sensitive HSV‐1 TAS was composed of 376 amino acids, while that of HSV‐1 TAR was composed of 407 amino acids with altered amino acid residue between positions 355–407. The elongation of TK was caused by a single nucleotide deletion of cytosine from a homopolymer stretch of 4 cytosine residues between positions 1061–1064. There was no viral TK activity in HSV‐1 TAR‐infected Vero cells, indicating the importance of the C‐terminal portion of TK protein from positions 355–376. Recombinant TK polypeptides with amino acid deletions at the C‐terminus were prepared, and TK and ACV‐phosphorylation activities were examined. Deletion of 5 and 6 amino acids from the C‐terminus of the TK polypeptide of HSV‐1 TAS resulted in a reduction of TK activity by approximately 75% and 100%, respectively. These mutant TK polypeptides did not phosphorylate ACV. These results indicate that amino acid residues from positions 371–376 in the C‐terminal portion of HSV‐1 TK protein are essential for keeping TK and ACV‐phosphorylation activities. J. Med. Virol. 66:388‐393, 2002. © 2002 Wiley‐Liss, Inc.