Background: The VP1 protein of enterovirus 71 (EV71) is an important immunodominant protein which is responsible for host-receptor binding. Nevertheless, the relationship between VP1 and neurovirulence is still poorly understood. In this study, we investigated the relationship between mutation of VP1 and neurovirulent phenotype of EV71 infection. Methods: One hundred and eighty-seven strains from Genbank were included, with a clear clinical background. They were divided into two groups, one with nervous system symptoms and one with no nervous system symptoms. After alignment, the significance of amino acid variation was determined by using the χ² test and a phylogenetic tree was constructed with MEGA software (version 5.1). Results: We showed no significant difference in neurovirulence between genotype B and C. Interestingly, we found that variations of E145G/Q, E164D/K and T292N/K were associated with nervous system infection in genotype B. In the case of genotype C, the N31D mutation increased the risk for nervous complications, whereas I262V mutation decreased the risk of nervous complications. We used a 3D model of VP1 to demonstrate the potential molecular basis for EV71 nervous system tropism. Conclusions: Distinct variations are shown to be associated with neurovirulent phenotype in the different genotype. Detection of variation in genotypes and subtypes may be important for the prediction of clinical outcomes.

Since 2015, 84 countries and territories reported evidence of vector-borne Zika Virus (ZIKV) transmission. The World Health Organization (WHO) declared that ZIKV and associated consequences especially the neurological autoimmune disorder Guillain–Barré syndrome (GBS) and microcephaly will remain a significant enduring public health challenge requiring intense action. We apply a standardization of the multi-subcutaneous dorsal inoculation method to systematically summarize clinical neurological manifestation, viral distribution, and tissue damage during the progress of viremia and systemic spread in suckling mouse models. We found that C57BL/6 and Kunming mice (KM) both showed remarkable and uniform neurologic manifestations. C57BL/6 owned the highest susceptibility and pathogenicity to the nervous system, referred to as movement disorders, with 100% incidence, while KM was an economic model for a Chinese study characterized by lower limb weakness with 62% morbidity. Slight yellow extraocular exudates were observed in BALB/c, suggesting the association with similar ocular findings to those of clinical cases. The virus distribution and pathological changes in the sera, brains, livers, kidneys, spleens, and testes during disease progression had strong regularity and uniformity, demonstrating the effectiveness and plasticity of the animal models. The successful establishment of these animal models will be conducive to expound the pathogenic mechanism of GBS.

Shiga toxin (Stx)-producing Escherichia coli (STEC) can cause a wide range of symptoms from asymptomatic carriage, mild diarrhea to bloody diarrhea (BD) and hemolytic uremic syndrome (HUS). Besides the Stx, intimin, encoded by the eae gene, also plays a critical role in STEC pathogenesis. Herein, we investigated the prevalence and genetic diversity of eae among clinical STEC strains isolated from patients with diarrhea, BD, HUS as well as from asymptomatic STEC-positive individuals in Sweden with whole-genome sequencing. We found that 173 out of 239 (72.4%) of clinical STEC strains were eae positive. Six eae subtypes (ϵ1, γ1, β3, θ, ζ and ρ) were identified, which were classified into 29 different genotypes. eae and its subtype γ1 were significantly overrepresented in O157:H7 strains isolated from BD and HUS patients. ϵ1 was associated with O121:H19 and O103:H2 strains, and β3 to O26:H11 strains. The presence of stx ₂+eae and stx ₁+stx ₂+eae was significantly more prevalent in strains from BD and HUS patients, respectively. The combination of a certain eae subtype (γ1) and stx subtype (stx ₂ or stx ₁+stx ₂) is more likely to cause severe disease, suggesting the possibility of using eae genotypes in risk assessment of STEC infection. No association was observed between the presence of eae or subtypes or duration of stx shedding. In summary, this study demonstrated a high prevalence of eae in clinical STEC strains and considerable genetic diversity of eae in STEC strains in Sweden from 1994 through 2018, and revealed association between eae subtypes and disease severity.

An avian-origin influenza H7N9 virus epidemic occurred in China in 2013‑2014, in which >422 infected people suffered from pneumonia, respiratory distress syndrome and septic shock. H7N9 viruses belong to the H7 subtype of avian‑origin influenza viruses (AIV-H7). Hemagglutinin (HA) is a vital membrane protein of AIV that has an important role in host recognition and infection. The epitopes of HA are significant determinants of the regularity of epidemic and viral mutation and recombination mechanisms. The present study aimed to predict the conserved B‑cell epitopes of AIV‑H7 HA using a bioinformatics approach, including the three most effective epitope prediction softwares available online: Artificial Neural Network based B‑cell Epitope Prediction (ABCpred), B‑cell Epitope Prediction (BepiPred) and Linear B‑cell Epitope Prediction (LBtope). A total of 24 strains of Euro‑Asiatic AIV‑H7 that had been associated with a serious poultry pandemic or had infected humans in the past 30 years were selected to identify the conserved regions of HA. Sequences were obtained from the National Center for Biotechnology Information and Global Initiative on Sharing Avian Influenza Data databases. Using a combination of software prediction and sequence comparisons, the conserved epitopes of AIV‑H7 were predicted and clarified. A total of five conserved epitopes [amino acids (aa) 37‑52, 131‑142, 215‑234, 465‑484 and 487‑505] with a suitable length, high antigenicity and minimal variation were predicted and confirmed. Each obtained a score of >0.80 in ABCpred, 60% in LBtope and a level of 0.35 in Bepipred. In addition, a representative amino acid change (glutamine235‑to‑leucine235) in the HA protein of the 2013 AIV‑H7N9 was discovered. The strategy adopted in the present study may have profound implications on the rapid diagnosis and control of infectious disease caused by H7N9 viruses, as well as by other virulent viruses, such as the Ebola virus.