Emergence of Herpes Simplex Virus-1 syncytial variants with altered virulence for mice after selection with a natural carrageenan

MATEU CECILIA; PEREZ RECALDE MERCEDES ; ARTUSO, CAROLINA; HERMIDA, GLADYS; LINERO, F; SCOLARO, LUIS; PUJOL, CARLOS; CARLUCCI, M J

SEXUALLY TRANSMITTED DISEASES

LIPPINCOTT WILLIAMS & WILKINS

Año: 2011 vol. 38 p. 555 - 561

0148-5717

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-á, interleukin-6, and IFN-ã 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.