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[Isolation and characteristics of a mutant herpes simplex virus type 1 resistant to phosphonoacetic acid]
Abstract:
By successive passages and triple cloning of herpes simplex virus type 1 (HSV-1) in Vero cell culture in the presence of increasing concentrations of phosphonoacetic acid (PAA) a mutant of HSV-1 resistant to PAA (PAAr) was derived and characterized. The resistance to the inhibitor was transmitted from PAAr-mutant to a sensitive strain (L2) by recombination performed by the marker rescue method using DNA fragmented by Hpa-1 restrictase. The resulting recombinant (R-551) was resistant to the inhibitor and had an altered primary structure of DNA.
Insights
Researchers developed a herpes simplex virus type 1 (HSV-1) mutant resistant to phosphonoacetic acid (PAA). This resistance was transferred to a sensitive HSV-1 strain, altering its DNA structure.
Area of Science:
- Virology
- Molecular Biology
- Genetics
Background:
- Herpes simplex virus type 1 (HSV-1) is a common human pathogen.
- Phosphonoacetic acid (PAA) is an inhibitor that affects viral DNA replication.
Purpose of the Study:
- To derive and characterize a PAA-resistant mutant of HSV-1.
- To investigate the genetic basis of PAA resistance in HSV-1.
Main Methods:
- Serial passages and cloning of HSV-1 in Vero cells with increasing PAA concentrations.
- Marker rescue recombination using Hpa-1 fragmented DNA.
- Characterization of the PAA-resistant mutant (PAAr) and recombinant (R-551).
Main Results:
- A mutant HSV-1 (PAAr) resistant to PAA was successfully derived.
- PAA resistance was transferable to a sensitive HSV-1 strain (L2) via recombination.
- The resulting recombinant (R-551) exhibited PAA resistance and an altered DNA primary structure.
Conclusions:
- The study successfully generated a PAA-resistant HSV-1 mutant.
- Genetic recombination can transfer PAA resistance, indicating a DNA-level alteration.
- This work provides insights into HSV-1 drug resistance mechanisms.