Use of Immunostimulatory Sequence-Containing Oligonucleotides as Topical Therapy for Genital Herpes Simplex Virus Type 2 Infection

Synthetic oligonucleotides containing CpG motifs in specific sequence contexts have been shown to induce potent immune responses. We have evaluated mucosal administration of two immunostimulatory sequence (ISS)-containing phosphorothioate-stabilized oligonucleotides for antiherpetic efficacy in animal models. The ISS oligonucleotides, suspended in phosphate-buffered saline, were tested in mouse and guinea pig vaginal models of herpes simplex virus type 2 (HSV-2) infection. For comparison, groups of untreated, non-ISS oligonucleotide-treated, and acyclovir-treated animals also were monitored. The results indicated that vaginal epithelial application of ISS (up to 6 h after viral inoculation) with mice lethally challenged with HSV-2 delayed disease onset and reduced the number of animals that developed signs of disease (P = 0.003). ISS application significantly increased survival rates over those of controls (P = 0.0014). The ISS also impacted an established infection in the guinea pig model of HSV-2 disease. A single administration of ISS (21 days after viral inoculation) significantly reduced the frequency and severity of HSV-2 lesions compared to results with non-ISS oligonucleotide-treated and untreated guinea pigs (P < 0.01). HSV-2 is shed from the vaginal cavity of the guinea pig in the absence of lesions, similar to the case with humans. As an additional indication of ISS efficacy, the magnitude of viral shedding also was significantly reduced in ISS-treated animals (P < 0.001). These effects appeared to be immunologically mediated, since ISS had no direct effect on HSV-2 replication in vitro using standard plaque assays. These data suggest that ISS may be useful in the treatment and control of genital herpes in humans

Metagenomic characterization of microbial communities on plasticized fabric materials exposed to harsh tropical environments

© 2020 Biodeterioration of plasticized fabrics is a serious problem leading to degradation of materials used in military and civilian applications. This study aimed to characterize the composition of the microbial communities present on six plasticized fabrics exposed to a harsh tropical environment and explore their role in biodeterioration. Metagenomics, bioinformatics, light and scanning electron microscopy (SEM), and solid-phase microextraction GC-MS were used to characterize the fabric-associated microbial communities and plasticizer degradation. SEM analysis showed multi-layered biofilms containing bacteria and a high abundance of fungal structures and yeast cells. Shotgun metagenomics with a multifaceted bioinformatic pipeline generated 3,314,688 contigs and 120 microbial genomes. The microbial genomes were classified into three domains with the majority belonging to fungi followed by bacteria, and archaea. Functional gene annotation revealed that the fabric-associated microbiomes harbor important pathways for energy generation, stress tolerance, and compounds degradation including esterases, lipases and monooxygenases, suggesting a role of these microorganisms in degradation. The results showed that black yeasts were the keystone species of microbiomes affecting the fabrics. Information from this study will help to understand the effect of different microbial communities and species on the biodeterioration of fabrics and may help support the development of new antimicrobial materials