Extracellular acidosis enhances Zika virus infection both in human cells and ex-vivo tissue cultures from female reproductive tract.

Zika virus (ZIKV) is a flavivirus transmitted by mosquitoes of the genus Aedes, but unlike other flaviviruses, ZIKV can be sexually transmitted by vaginal intercourse. The healthy vaginal pH ranges from 4.0 to 6.0, reaching values of 6.0-7.0 after semen deposition. Here, we report that low extracellular pH values (range 6.2-6.6) dramatically increase ZIKV infection on cell lines of different origin including some derived from the female genital tract and monocyte-derived macrophages. Furthermore, low pH significantly increased ZIKV infection of human ectocervix and endocervix cultured ex-vivo. Enhancement of infection by low pH was also observed using different ZIKV strains and distinct methods to evaluate viral infection, i.e. plaque assays, RT-PCR, flow cytometry, and fluorescence microscopy. Analysis of the mechanisms involved revealed that the enhancement of ZIKV infection induced by low pH was associated with increased binding of the viral particles to the heparan sulphate expressed on the target cell surface. Acidosis represents a critical but generally overlooked feature of the female genital tract, with major implications for sexual transmission diseases. Our results suggest that low vaginal pH might promote male-to-female transmission of ZIKV infection.

Modelling inactivation of wild-type and clinical Escherichia coli O26 strains using UV-C and thermal treatment and subsequent persistence in simulated gastric fluid.

AIMS: First, two inactivation models were compared for different phenotypic profiles of Escherichia coli O26 using ultraviolet-C light (UV-C) and thermal treatment (T), by means of Central Composite Rotatable Design of Experiment (CCRD). Second, we aimed to evaluate the subsequent survival and persistence of cells in simulated gastric fluid (SGF). METHODS AND RESULTS: Two strains of E. coli O26, a wild-type strain and a clinical ATCC strain were used in both steps. A CCRD was used in a 22 arrangement in random order. The goodness-of-fit of the models was determined. The lack of fit, and the normality of residual data were checked with the Shapiro-Wilk test, and the model accuracy factor, bias factor and the model mean square error (MSE) were measured. Subsequently, the resistance capacity of the strains was evaluated after exposure to simulated gastric acid. The CCRD results obtained indicate that the mild heat (<70°C) has a recovery effect. In addition, for the clinical strain, the UV-C and heat (above 70°C) has an additive inactivation effect. Moreover, temperature (65°C) induced SGF resistance by the wild-type and clinical strain. For the clinical strain, cells exposed to UV-C were more sensitive to SGF. In contrast to clinical strain, exposing cells of the wild-type strain to UV-C increased the survival capacity in the SGF. CONCLUSION: Response surface analyses showed that the wild-type O26 strain has higher persistence under unfavourable conditions than the clinical strain, and the stresses caused by applied microbial control technologies can increase the survival capacity in the SGF. SIGNIFICANCE AND IMPACT OF THE STUDY: The present study shed light on different phenotypic responses in the same bacterium serogroup. Moreover, the impact of the study was that strain selection criteria must be adequate to develop effective models of inactivation.

Seminal vesicle fluid increases the efficacy of intravaginal HSV-2 vaccination.

Once considered merely as a vehicle for spermatozoa, it is now clear that seminal plasma (SP) induces a variety of biological actions on the female reproductive tissues able to modulate the immune response against paternal antigens. To our knowledge, the influence of SP on the immune response against sexually transmitted pathogens has not been yet evaluated. We here analyzed whether the seminal vesicle fluid (SVF), which contributes almost 60% of the SP volume in mice, could modulate the immune response against herpes simplex virus type 2 (HSV-2). We found that SVF does not modify the course of primary infection, but markedly improved protection conferred by vaginal vaccination with inactivated HSV-2 against a lethal challenge. This protective effect was shown to be associated to a robust memory immune response mediated by CD4+ and CD8+ T cells in both the lymph nodes draining the vagina and the vaginal mucosa, the site of viral replication. In contrast with the widespread notion that SP acts as an immunosuppressive agent, our results suggest that SVF might improve the female immune response against sexually transmitted pathogens.