title: Evidence of Muller's ratchet in herpes simplex virus type 1.
abstract: Population bottlenecks can have major effects in the evolution of RNA viruses, but their possible influence in the evolution of DNA viruses is largely unknown. Genetic and biological variation of herpes simplex virus type 1 (HSV-1) has been studied by subjecting 23 biological clones of the virus to 10 plaque-to-plaque transfers. In contrast to large population passages, plaque transfers led to a decrease in replicative capacity of HSV-1. Two out of a total of 23 clones did not survive to the last transfer in 143 TK(-) cells. DNA from three genomic regions (DNA polymerase, glycoprotein gD and thymidine kinase) from the initial and passaged clones was sequenced. Nucleotide substitutions were detected in the TK and gD genes, but not in the DNA polymerase gene. Assuming a uniform distribution of mutations along the genome, the average rate of fixation of mutations was about five mutations per viral genome and plaque transfer. This value is comparable to the range of values calculated for RNA viruses. Four plaque-transferred populations lost neurovirulence for mice, as compared with the corresponding initial clones. LD(50) values obtained with the populations subjected to serial bottlenecks were 4- to 67-fold higher than for their parental clones. These results equate HSV-1 with RNA viruses regarding fitness decrease as a result of plaque-to-plaque transfers, and show that population bottlenecks can modify the pathogenic potential of HSV-1. Implications for the evolution of complex DNA viruses are discussed.
authors.affiliation: Departamento de Medicina Preventiva Salud Pública y Microbiología, Facultad de Medicina, UAM, Madrid, Spain.
authors.forename: Nacarí
authors.initials: N
authors.lastname: Jaramillo
authors.affiliation: Centro de Investigación en Red de Enfermedades Hepáticas y Digestivas (CIBER ehd), Barcelona, Spain.|Centro de Biología Molecular 'Severo Ochoa' (Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid) Universidad Autónoma de Madrid, Cantoblanco, Madrid, Spain.
authors.forename: Esteban
authors.initials: E
authors.lastname: Domingo
authors.affiliation: Fundación Jiménez Díaz, Madrid, Spain.
authors.forename: María Carmen
authors.initials: MC
authors.lastname: Muñoz-Egea
authors.affiliation: Departamento de Medicina Preventiva Salud Pública y Microbiología, Facultad de Medicina, UAM, Madrid, Spain.
authors.forename: Enrique
authors.initials: E
authors.lastname: Tabarés
authors.affiliation: Fundación Jiménez Díaz, Madrid, Spain.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Gadea
mesh_terms: D000818:Animals; D004279:DNA, Viral / Q000235:genetics; D004195:Disease Models, Animal; D019143:Evolution, Molecular; D005260:Female; D014644:Genetic Variation; D006561:Herpes Simplex / Q000473:pathology / Q000821:virology; D018259:Herpesvirus 1, Human / Q000145:classification / Q000235:genetics* / Q000472:pathogenicity; D007928:Lethal Dose 50; D051379:Mice; D059645:Mutation Rate; D017354:Point Mutation; D017422:Sequence Analysis, DNA; D012692:Serial Passage; D016019:Survival Analysis; D014764:Viral Proteins / Q000235:genetics
chemical_list: D004279:DNA, Viral; D014764:Viral Proteins