A virologist is researching acyclovir-resistant herpes simplex virus (HSV). Viral DNA analysis reveals a mutation in the thymidine kinase gene, resulting in a mutated enzyme that does not phosphorylate acyclovir to its active form. In an experiment, a resistant HSV type 2 strain containing this mutation is cultured in a cell line, and the cell culture is coinfected with a nonresistant HSV type 1 strain. It is found that some of the newly produced type 1 virions acquire resistance to acyclovir, and subsequent progeny continue to be resistant. Which of the following mechanisms best explains the observed findings?
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This scenario describes the exchange of genetic information between 2 virus strains that have nonsegmented, double-stranded DNA genomes. Recombination refers to the exchange of genes between 2 chromosomes via crossing over within homologous regions. The resulting progeny can have recombined genomes with traits from both parent viruses. In this case, the thymidine kinase genes in HSV type 1 and 2 virions are likely to have significant sequence similarity, allowing cross over to occur with relatively high frequency.
(Choice A) Interference occurs when one virus inhibits replication and/or release of a second virus that is infecting the same cell. Simple interference would not result in recombinant progeny virions.
(Choice B) Phenotypic mixing can occur when a host cell is coinfected with 2 viral strains and progeny virions contain parental genome from one strain and nucleocapsid (or envelope) proteins from the other strain. This may result in progeny acquiring additional traits (eg, enhanced ability to infect new host cells due to different nucleocapsid proteins). However, as the genome is unchanged, subsequent progeny would not retain these traits.
(Choice C) Reassortment refers to changes in genomic composition that occur when host cells are coinfected with 2 segmented viruses that exchange whole genome segments. This process can cause sudden alterations in surface antigens of the viral progeny, as observed with the highly mutagenic influenza virus. However, because the herpesvirus genome is nonsegmented, it does not engage in reassortment.
(Choice E) Transformation is the uptake of naked DNA by a prokaryotic or eukaryotic cell. In virology, transformation also describes incorporation of viral DNA into a host cell chromosome (lysogeny). Transformation alters the genetic composition of the host cell but typically causes no genomic change in progeny virions.
Educational objective:
Recombination refers to gene exchange that occurs through the crossing over of 2 double-stranded DNA molecules. Reassortment describes the mixing of genome segments in segmented viruses that infect the same host cell.