Antiviral Effect Of PSM Against Herpes Simplex Virus Type2

Herpes simplex type Ⅱ (HSV-2), a double stranded linear DNA virus, is a member of the herpesviridae family. HSV-2is transmitted mainly through sexual route and is one of the most prevalent sexually transmitted diseases globally. Most of the infection is not fatal and interspersed with asymptomatic latency and clinically active viral replication. HSV-2infection results in genital microleisions and mucosal inflammation and is demonstrated epidemiologically to be a risk factor for HIV-1transmission. A meta-analysis also demonstrated that HSV-2infection also influences the disease progression in the HIV-1infection population. The existing treatment with acyclovir when applied early in the infection will only reduce the frequency of recurring viral replication and lessen severity of the disease but will not cure or clear the virus. From the point view of public health, the most cost effective and efficient approach is to prevent HSV-2transmission at the entry portal. However, current vaccine is of limited efficacy and an effective entry inhibitory drug is still elusive. Therefore, effective drugs are critically needed. To explore how Poly (4-styrenesulfonic acid-co-maleic acid)(PSM) blocks HSV-2infection, in vitro and in vivo researches were carried out as following:1.After the pGL4plasmid containing the recombinant ICP10-promoter was constructed, Vero cells were treated with different concentrations of PSM (60.20、6.67、2.2、0.74、0.25、0.08ug/mL), followed by50uL HSV-2(MOI=1). Luciferase analysis of ICP10-promoter was performed to measure the virus replication in vitro. The results showed that PSM could inhibit HSV-2infection of the Vero cells.2.gD protein was analyzed in an In-Cell-Western assay to show the inhibitory effects of PSM on HSV-2infection of HEC-1-A cells. The results showed that PSM could inhibit HSV-2infection of HEC-1-A cells.3.A mouse model was developed to investigate the in vivo efficacy of PSM in protecting the animals from HSV-2infection via vaginal route. The results showed that PSM offered significant protection of the mice against the vaginal infection of a pathogenic HSV-2strain (P<0.001).The above experimental results show that PSM could be a potential candidate for the treatment against HSV-2, and further research is needed to expand the scope of the investigation and for a thorough evaluation of toxicity.