Departamento de Química Biológica, Laboratorio de Virologia, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina.
Sex Transm Dis. 2011 Jun;38(6):555-61.
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.
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.
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.
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.
以角叉菜聚糖为代表的基于硫酸化多糖的抗单纯疱疹病毒疗法为生殖器疱疹感染的治疗提供了一种新的选择，但这也引起了人们对耐药病毒群体出现的担忧。
我们对在分离自红海巨藻 Gigartina skottbergii 的天然角叉菜聚糖存在的情况下传代的单纯疱疹病毒 1 型 F 株进行了表征，目的是研究分离的病毒克隆对小鼠的毒力。
病毒克隆（syn14-1 和 syn17-2）表现出合胞体表型和对角叉菜聚糖、肝素、阿昔洛韦和溴夫定的轻度耐药性。当阴道内接种时，这两个克隆对 BALB/c 小鼠均无致病性，而 F 株则导致高死亡率。减毒与阴道灌洗液中 TNF-[alpha]、白细胞介素 6 和 IFN-[gamma]水平低相关，尽管病毒滴度与 F 株相似。相反，当鼻腔内接种时，它们表现出明显的毒力，导致病毒广泛传播。
结果证实了这样一种假设，即在体外用角叉菜聚糖选择单纯疱疹病毒 1 株会导致出现与原始病毒相比具有不同毒力的变异株。在考虑使用天然角叉菜聚糖对抗生殖器疱疹感染的抗病毒治疗时，应注意这一发现。
