Phenotypic and genotypic characterization of acyclovir-resistant herpes simplex viruses from immunocompromised patients.
Phenotypic and genotypic analyses were done on 30 acyclovir-resistant and 5 acyclovir-susceptible herpes simplex virus (HSV) isolates (22 HSV type 1 and 13 HSV type 2) recovered from 24 subjects. All isolates were susceptible to foscarnet. The phenotypes of the acyclovir-resistant HSV isolates were as follows: 17 were thymidine kinase (TK) deficient, 12 had decreased TK activity (produced low amounts of viral TK) or TK with altered substrate specificity, and 1 was undetermined. Sequencing analysis of the HSV TK gene revealed that 14 (46.7%) of 30 acyclovir-resistant isolates had an insertion or deletion of 1 or 2 nucleotides, especially in homopolymer runs of Gs, Cs, and rarely in As. On the other hand, 16 (53.3%) of 30 acyclovir-resistant isolates had point mutations in conserved or nonconserved regions of the TK gene. In conclusion, HSV can develop multiple strategies to exhibit acyclovir resistance, including, in about half of the cases, frameshift mutations in homopolymer nucleotide stretches of the TK gene.
Division of Microbiology, Centre Hospitalier Universitaire de Québec and Laval University, Québec City, Canada.
A
A
Gaudreau
E
E
Hill
H H
HH
Balfour
A
A
Erice
G
G
Boivin
D017088:AIDS-Related Opportunistic Infections / Q000276:immunology / Q000821:virology; D000212:Acyclovir / Q000494:pharmacology*; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D002522:Chlorocebus aethiops; D004352:Drug Resistance, Microbial; D005838:Genotype; D006558:Herpes Genitalis / Q000188:drug therapy / Q000276:immunology / Q000821:virology; D006561:Herpes Simplex / Q000188:drug therapy / Q000276:immunology / Q000821:virology*; D018259:Herpesvirus 1, Human / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics / Q000302:isolation & purification; D018258:Herpesvirus 2, Human / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D016867:Immunocompromised Host; D010641:Phenotype; D013937:Thymidine Kinase / Q000235:genetics* / Q000378:metabolism*; D014181:Transplantation Immunology; D014709:Vero Cells
D000998:Antiviral Agents; D013937:Thymidine Kinase; D000212:Acyclovir