Mumps outbreaks among vaccinated patients have become increasingly common in recent years. While there are multiple conditions driving this re-emergence, convention has suggested that these outbreaks are associated with waning immunity rather than vaccine escape. Molecular evidence from both the ongoing American and Dutch outbreaks in conjunction with recent structural biology studies challenge this convention, and suggest that emergent lineages of mumps virus exhibit key differences in antigenic epitopes from the vaccine strain employed: Jeryl-Lynn 5. The American and Dutch 2016-2017 outbreak lineages were examined using computational biology through the lens of diversity in immunogenic epitopes. Findings are discussed and the laboratory evidence indicating neutralization of heterologous mumps strains by serum from vaccinated individuals is reviewed. Taken together, it is concluded that the number of heterologous epitopes occurring in mumps virus in conjunction with waning immunity is facilitating small outbreaks in vaccinated patients, and that consideration of a polyvalent mumps vaccine is warranted.

Zika virus (ZIKV) recently emerged in the Western Hemisphere with previously unrecognized or unreported clinical presentations. Here, we identify two putative binding mechanisms of ancestral and emergent ZIKV strains featuring the envelope (E) protein residue asparagine 154 (ASN154) and viral phosphatidylserine (PS). Synthetic peptides representing the region containing ASN154 from strains PRVABC59 (Puerto Rico 2015) and MR_766 (Uganda 1947) were exposed to neuronal cells and fibroblasts to model ZIKV E protein/cell interactions and bound MDCK or Vero cells and primary neurons significantly. Peptides significantly inhibited Vero cell infectivity by ZIKV strains MR_766 and PRVABC59, indicating that this region represents a putative binding mechanism of ancestral African ZIKV strains and emergent Western Hemisphere strains. Pretreatment of ZIKV strains MR_766 and PRVABC59 with the PS-binding protein annexin V significantly inhibited replication of PRVABC59 but not MR_766, suggesting that Western hemisphere strains may additionally be capable of utilizing PS-mediated entry to infect host cells. These data indicate that the region surrounding E protein ASN154 is capable of binding fibroblasts and primary neuronal cells and that PS-mediated entry may be a secondary mechanism for infectivity utilized by Western Hemisphere strains.

26Zika virus (ZIKV) recently emerged in the Western Hemisphere with previously unrecognized or 27unreported clinical presentations. Here, we identify two distinct binding mechanisms of ancestral and 28 emergent ZIKV strains featuring the envelope (E) protein residue ASN154 and viral phosphatidylserine 29 (PS). Short (20-mer) peptides representing the region containing ASN154 from strains PRVABC59 (Puerto 30Rico 2015) and MR_766 (Uganda 1947) were exposed to neuronal cells and fibroblasts, expecting 31interactions to be representative of ZIKV E protein/cell interactions, and bound MDCK or Vero cells and 32 primary neurons significantly above a scrambled PRVABC59 control peptide. Peptides also significantly 33 inhibited Vero cell adsorption by ZIKV strains MR_766 and PRVABC59, indicating that we have identified 34 a binding mechanism of ancestral African ZIKV strains and emergent Western Hemisphere strains. 35Pretreatment of ZIKV MR_766 and PRVABC59 with the PS-binding protein annexin V significantly 36 inhibited replication of PRVABC59, but not MR_766, suggesting that Western hemisphere strains are 37 additionally utilizing PS-mediated entry to infect host cells. Taken together, these data indicate that we 38have identified an ancestral binding mechanism of ZIKV, and a secondary binding mechanism utilized by 39Western Hemisphere strains. 40 41Background 42

Given the reported effects of gut microbiome modulation on local gut inflammation and intestinal pain, it is possible that gut microbiota regulate persistent or chronic pain conditions that are distal to the gut, including pain states in the extremities. This study evaluated the effects of gut microbiome modulation on formalin pain‐depressed behaviors and formalin‐induced paw inflammation in female Fisher rats. Pilot data indicate that (1) a two‐week regimen of the narrow‐spectrum gram‐positive antibiotic vancomycin (500mg/L) in drinking water depleted Firmicutes and Bacteroidetes diversity / density in rats with or without access to running wheels; (2) formalin alone (0.5, 2.5, 5%) produced concentration‐dependent biphasic licking behavior of injured hind paw across 60 min and concentration‐dependent depression of voluntary wheel running for 7 consecutive days; (3) two‐week antibiotic treatment prior to formalin administration had a protective effect manifested as attenuation of Phase II formalin scores, and complete reversal of formalin pain‐depressed wheel running for 7 consecutive days; (4) the protective effects of vancomycin on formalin pain‐related outcomes were associated with divergent changes to proteobacteria in sedentary vs. voluntary exercised rats. These data indicate that a narrow spectrum gram‐positive antibiotic can have lasting protective effects on persistent pain‐related behaviors and that associated changes to gut microbiota vary as a function of sedentary vs. exercise condition. Parallel mechanistic studies are currently assessing the efficacy of probiotic and fecal microbiota transplant procedures vs. opioid compounds to block antibiotic‐induced modulation to formalin pain‐related outcomes.Support or Funding InformationThis research supported by a NIH COBRE grant (P20GM103643) that supports an animal behavior core facility, and a COBRE Pilot award and NIAMS R15 AREA grant (AR054975) to G.W.S.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.