Streptococcus suis serotype 2 (S. suis 2) is a highly invasive pathogen in pigs and humans that can cause severe systemic infection. Sepsis and meningitis are the most common clinical manifestations of S. suis 2 infection. However, the mechanisms of S. suis 2 surviving in human blood remains unclear, so to identify novel virulence factors in evasion of polymorphonuclear leukocyte (PMN)-mediated innate immunity play important roles in developing therapies against S. suis 2 infection. Here, we found that S. suis 2 can escape phagocytic clearance by adenosine synthesis in blood. Through bioinformatics-based analyses we identified a cell wall-anchored protein harbors a 5′-nucleotidase signature sequence and evidence strongly indicated that it can convert adenosine monophosphate (AMP) to adenosine. It was designated as Ssads (the adenosine synthase of S. suis 2). Furthermore, we found that Ssads could impair PMN's defense against S. suis 2 with decreasing of oxidative activity and degranulation of PMNs in human blood via A₂a receptors. Additionally, this enzyme-deficient mutant was found to have diminished virulence in the piglet infection model. Taken together, these results indicate that Ssads play an important role in S. suis 2 escaping human innate immunity in the context of inhibiting PMN's activity by synthesis of adenosine.

Since 2013, highly pathogenic avian influenza H5N6 viruses have emerged in poultry and caused sporadic infections in humans, increasing global concerns regarding their potential as human pandemic threats. Here, we characterized the receptor-binding specificities, pathogenicities and transmissibilities of three H5N6 viruses isolated from poultry in China. The surface genes hemagglutinin (HA) and neuraminidase (NA) were closely related to the human-originating strain A/Changsha/1/2014 (H5N6). Phylogenetic analyses showed that the HA genes were clustered in the 2.3.4.4 clade, and the NA genes were derived from H6N6 viruses. These H5N6 viruses bound both α-2,3-linked and α-2,6-linked sialic acid receptors, but they exhibited different pathogenicities in mice. In addition, one virus was fully infective and transmissible by direct contact in guinea pigs. These results highlight the importance of monitoring the continual adaptation of H5N6 viruses in poultry due to their potential threat to human health.

Most of the deaths that occurred during two large outbreaks of Streptococcus suis infections in 1998 and 2005 in China were caused by streptococcal toxic shock syndrome (STSS), which is characterized by increased vascular permeability. Heparin-binding protein (HBP) is thought to mediate the vascular leakage. The purpose of this study was to investigate the detailed mechanism underlying the release of HBP and the vascular leakage induced by S. suis. Significantly higher serum levels of HBP were detected in Chinese patients with STSS than in patients with meningitis or healthy controls. Suilysin (SLY) is an exotoxin secreted by the highly virulent strain 05ZYH33, and it stimulated the release of HBP from the polymorphonuclear neutrophils and mediated vascular leakage in mice. The release of HBP induced by SLY was caused by a calcium influx-dependent degranulation. Analyses using a pharmacological approach revealed that the release of HBP induced by SLY was related to Toll-like receptor 4, p38 mitogen-activated protein kinase, and the 1-phosphatidylinositol 3-kinase pathway. It was also dependent on a G protein-coupled seven-membrane spanning receptor. The results of this study provide new insights into the vascular leakage in STSS associated with non-Group A streptococci, which could lead to the discovery of potential therapeutic targets for STSS associated with S. suis.

https://www.wsj.com/articles/ u-k-delays-second-covid-19-vaccine-dose-as-europeponders-how-to-speed-up-immunization-11609334172 8. US Food and Drug Administration. FDA statement on following the authorized dosing schedules for COVID-19 vaccines. January 4, 2021 [cited 2021 Jan 14]. https://www. fda.gov/news-events/press-announcements/fda-statementfollowing-authorized-dosing-schedules-covid-19-vaccines 9. Livingston EH. Necessity of 2 doses of the Pfizer and

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