Emergence of HSV-1 sincytial variants with altered virulence for mice after selection with a natural carrageenan

CECILIA GABRIELA MATEU, MERCEDES PEREZ RECALDE, GLADYS HERMIDA, CAROLINA ARTUSO, CARLOS PUJOL, ELSA DAMONTE, JOSEFINA CARLUCCI

SEXUALLY TRANSMITTED DISEASES

LIPPINCOTT WILLIAMS & WILKINS

Año: 2011 vol. 38 p. 548 - 554

0148-5717

Background: Antiviral therapy against herpes simplex virus based on sulfated polysaccaharides, like carrageenans, represents a new alternative for genital herpes infections treatment and arises the concern about the appearance of resistant viral populations.Antiviral therapy against herpes simplex virus based on sulfated polysaccaharides, 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 HSV-1 passaged in the presence of a natural carrageenan isolated form 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-ƒÑ, IL-6 and IFN-ƒ× 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 HSV-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.We characterized the F strain of HSV-1 passaged in the presence of a natural carrageenan isolated form 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-ƒÑ, IL-6 and IFN-ƒ× 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 HSV-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.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-ƒÑ, IL-6 and IFN-ƒ× 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 HSV-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.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-ƒÑ, IL-6 and IFN-ƒ× 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 HSV-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.ƒÑ, IL-6 and IFN-ƒ× 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 HSV-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.Conclusions: Results confirm the hypothesis that selection of HSV-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.