This report evaluates a dietary manipulation approach to suppress the severity of ocular infections caused by herpes simplex virus infection. The virus causes chronic damage to the cornea that results from a T cell orchestrated inflammatory reaction to the infection. Lesion severity can be limited if cells with regulatory activity predominate over proinflammatory T cells and non-lymphoid inflammatory cells. In this report, we show that this outcome can be achieved by including the short chain fatty acid salt sodium propionate (SP) in the drinking water. Animals given the SP supplement developed significantly reduced ocular lesions than those receiving no supplement. Corneas and lymphoid organs contained fewer CD4 Th1 and Th17 T cells, neutrophils and macrophages than controls, but a higher frequency of regulatory T cells (Treg) was present. The inclusion of SP in cultures to induce CD4 T cell subsets in-vitro reduced the magnitude of Th1 and Th17 responses but expanded Treg induction. Diet manipulation was an effective approach to limit the severity of viral immuno-inflammatory lesions and may be worth exploring as a means to reduce the impact of herpetic lesions in humans. IMPORTANCE Herpetic lesions are a significant problem in several persons and they are difficult to control with therapeutics. Our studies show that the severity of herpetic lesions in a mouse model can be diminished by changing the diet to include increased levels of SCFA which acts to inhibit the involvement of inflammatory T cells. We suggest that changing the diet to include higher levels of SCFA might be a useful approach to reduce the impact of recurrent herpetic lesions in humans.

Zoonotic coronaviruses have caused several endemic and pandemic situations around the world. SARS caused the first epidemic alert at the beginning of this century, followed by MERS. COVID-19 appeared to be highly contagious, with human-to-human transmission by aerosol droplets, and reached nearly all countries around the world. A plethora of studies were performed, with reports being published within a short period of time by scientists and medical physicians. It has been difficult to find the relevant data to create an overview of the situation according to studies from accumulated findings and reports. In the present study we aimed to perform a comprehensive study in the context of the case fatality ratios (CFRs) of three major human Coronavirus outbreaks which occurred during the first twenty years of 21st century. In this study, we performed meta-analyses on SARS, MERS and COVID-19 outbreak events from publicly available records. Study analyses were performed with the help of highly reputable scientific databases such as PubMed, WOS and Scopus to evaluate and present current knowledge on zoonotic coronavirus outbreaks, starting from 2000 to the end of 2020. A total of 250,194 research studies and records were identified with specific keywords and synonyms for the three viruses in order to cover all publications. In the end, 41 records were selected and included after applying several exclusion and inclusion criteria on identified datasets. SARS was found to have a nearly 11% case fatality ratio (CFR), which means the estimated number of deaths as a proportion of confirmed positive cases; Taiwan was the country most affected by the SARS outbreak based on the CFR analysis. MERS had CFRs of 35.8 and 26 in Saudi Arabia during the 2012 and 2015 outbreaks, respectively. COVID-19 resulted in a 2.2 CFR globally, and the USA reported the highest mortality ratio in the world in the end of first year of COVID-19 pandemic. Some members of the Coronaviridae family can cause highly contagious and devastating infections among humans. Within the last two decades, the whole world has witnessed several deadly emerging infectious diseases, which are most commonly zoonotic in nature. We conclude that pre-existing immunity during the early stages of a pandemic might be important, but case control and management strategies should be improved to decrease CFRs. Finally, we have addressed several concerns in relation to outbreak events in this study.

This report evaluates how HSV enters the brain to cause herpes simplex encephalitis following infection at a peripheral site. We demonstrate that encephalitis regularly occurred when BALB/c mice were infected with HSV and treated daily with 2-deoxy-d-glucose (2DG), which inhibits glucose use via the glycolysis pathway. The outcome of infection in the trigeminal ganglion (TG), the site to which the virus spreads, replicates, and establishes latency, showed marked differences in viral and cellular events between treated and untreated animals. In control-untreated mice, the replicating virus was present only during early time points, whereas in 2DG recipients, replicating virus remained for the 9-d observation period. This outcome correlated with significantly reduced numbers of innate inflammatory cells as well as T cells in 2DG-treated animals. Moreover, T cells in the TG of treated animals were less activated and contained a smaller fraction of expressed IFN-γ production compared with untreated controls. The breakdown of latency was accelerated when cultures of TG cells taken from mice with established HSV latency were cultured in the presence of 2DG. Taken together, the results of both in vivo and in vitro investigations demonstrate that the overall effects of 2DG therapy impaired the protective effects of one or more inflammatory cell types in the TG that normally function to control productive infection and prevent spread of virus to the brain.