title: Emergence of herpes simplex virus-1 syncytial variants with altered virulence for mice after selection with a natural carrageenan.
abstract: BACKGROUND
  Antiviral therapy against herpes simplex virus based on sulfated polysaccharides, like carrageenans, represents a new alternative for genital herpes infections treatment and arises the concern about the appearance of resistant viral populations.
  
  
  METHODS
  We characterized the F strain of herpes simplex virus-1 passaged in the presence of a natural carrageenan isolated from the red seaweed Gigartina skottbergii in view of the virulence for mice of isolated viral clones.
  
  
  RESULTS
  Viral clones (syn14-1 and syn17-2) showed a syncytial phenotype and a mild resistance to carrageenan, heparin, acyclovir, and brivudine. Both clones were avirulent for BALB/c mice when inoculated intravaginally, whereas F strain produced high mortality. Attenuation correlated with low levels of TNF-[alpha], interleukin-6, and IFN-[gamma] in vaginal lavages although virus titers were similar to those obtained for F strain. On the contrary, they showed a marked virulence when inoculated intranasally leading to a generalized spreading of virus.
  
  
  CONCLUSIONS
  Results confirm the hypothesis that selection of herpes simplex virus-1 with a carrageenan in vitro leads to the emergence of variants with a differential virulence when compared to the original virus. This finding should be addressed when an antiviral therapy against genital herpes infection employing a natural carrageenan is under consideration.
authors.affiliation: Departamento de Química Biológica, Laboratorio de Virologia, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Cecilia G
authors.initials: CG
authors.lastname: Mateu
authors.forename: Mercedes Perez
authors.initials: MP
authors.lastname: Recalde
authors.forename: María C
authors.initials: MC
authors.lastname: Artuso
authors.forename: Gladys
authors.initials: G
authors.lastname: Hermida
authors.forename: Florencia N
authors.initials: FN
authors.lastname: Linero
authors.forename: Luis A
authors.initials: LA
authors.lastname: Scolaro
authors.forename: Elsa B
authors.initials: EB
authors.lastname: Damonte
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Pujol
authors.forename: María J
authors.initials: MJ
authors.lastname: Carlucci
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002351:Carrageenan / Q000494:pharmacology*; D002522:Chlorocebus aethiops; D005260:Female; D014644:Genetic Variation; D015726:Giant Cells / Q000502:physiology*; D006558:Herpes Genitalis / Q000473:pathology / Q000821:virology; D006561:Herpes Simplex / Q000473:pathology / Q000821:virology; D018259:Herpesvirus 1, Human / Q000145:classification / Q000187:drug effects / Q000235:genetics / Q000472:pathogenicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008826:Microbial Sensitivity Tests; D000461:Rhodophyta / Q000737:chemistry; D012624:Seaweed / Q000737:chemistry; D012641:Selection, Genetic; D014709:Vero Cells; D014774:Virulence
chemical_list: D000998:Antiviral Agents; D002351:Carrageenan