Enterovirus D68 (EV-D68) is a member of the Picornaviridae family. Although EV-D68-associated infection was once considered rare, it has been increasing in recent years. EV-D68 infection is most frequently associated with respiratory illness. However, it has also been implicated in a polio-like neurological disorder, acute flaccid myelitis. Although sialic acid has been implicated in EV-D68 entry, the existence of a protein receptor has yet to be clarified. Here we identify neuron-specific intercellular adhesion molecule 5 (ICAM-5/telencephalin) as a cellular receptor for sialic acid-dependent and -independent EV-D68 viruses. EV-D68 bound specifically and efficiently to ICAM-5, and replication of EV-D68 in diverse cell types was inhibited by soluble ICAM-5 fragments. ICAM-5 silencing attenuated EV-D68 replication in permissive cells, and ICAM-5 expression in non-permissive cells allowed EV-D68 replication. The discovery of a neuron-specific adhesion molecule as an EV-D68 receptor has important implications for EV-D68 pathogenesis and may facilitate the development of novel intervention strategies.

Influenza viral passaging through pre-vaccinated mice shows that emergent antigenic site mutations on the viral hemagglutinin (HA) impact host receptor-binding affinity and, therefore, the evolution of fitter influenza strains. To understand this phenomenon, we computed the Significant Interactions Network (SIN) for each residue and mapped the networks of antigenic site residues on a representative H1N1 HA. Specific antigenic site residues are ‘linked’ to receptor-binding site (RBS) residues via their SIN and mutations within “RBS-linked” antigenic residues can significantly influence receptor-binding affinity by impacting the SIN of key RBS residues. In contrast, other antigenic site residues do not have such “RBS-links” and do not impact receptor-binding affinity upon mutation. Thus, a potential mechanism emerges for how immunologic pressure on RBS-linked antigenic residues can contribute to evolution of fitter influenza strains by modulating the host receptor-binding affinity.

This study is a case for better understanding the intriguing roles of ion/neutral complexes in gas-phase fragmentation reactions and enriching the knowledge about the gas-phase chemistry of the benzyl cation. In addition, it provides useful information for researchers working on analysis or structural elucidation of complicated compounds which contain the N-benzyltetrahydroquinoline substructure.

Avian influenza A(H7N9) virus (A(H7N9)) emerged in February 2013. Liver impairment of unknown cause is present in 29% of patients with A(H7N9) infection, some of whom experience severe liver injury. Hypoxic hepatitis (HH) is a type of acute severe liver injury characterized by an abrupt, massive increase in serum aminotransferases resulting from anoxic centrilobular necrosis of liver cells. In the intensive care unit (ICU), the prevalence of HH is ∼1%–2%. Here, we report a 1.8% (2/112) incidence of HH in the largest single-centre cohort of ICU patients with A(H7N9) infection. Both HH patients presented with multiple organ failure (MOF) involving respiratory, cardiac, circulatory and renal failure and had a history of chronic heart disease. On admission, severe liver impairment was found. Peak alanine aminotransferase (ALT) and aspartate aminotransferase (AST) values were 937 and 1281 U/L, and 3117 and 3029 U/L, respectively, in the two patients. Unfortunately, both patients died due to deterioration of MOF. A post-mortem biopsy in case 1 confirmed the presence of centrilobular necrosis of the liver, and real-time reverse transcription polymerase chain reaction of A(H7N9)-specific genes was negative, which excluded A(H7N9)-related hepatitis. The incidence of HH in A(H7N9) patients is similar to that in ICU patients with other aetiologies. It seems that patients with A(H7N9) infection and a history of chronic heart disease with a low left ventricular ejection fraction on admission are susceptible to HH, which presents as a marked elevation in ALT at the time of admission.

The two patients from one family cluster were probable human-to-human transmission cases. The new isolates were sensitive to peramivir but showed reduced sensitivity to oseltamivir.