Influenza A virus (IAV) membrane proteins hemagglutinin (HA) and neuraminidase (NA) are determinants of virus infectivity, transmissibility, pathogenicity, host specificity, and major antigenicity. HA binds to a virus receptor, a sialoglycoprotein or sialoglycolipid, on the host cell and mediates virus attachment to the cell surface. The hydrolytic enzyme NA cleaves sialic acid from viral receptors and accelerates the release of progeny virus from host cells. In this study, we identified a novel function of HA and NA as machinery for viral motility. HAs exchanged binding partner receptors iteratively, generating virus movement on a receptor-coated glass surface instead of a cell surface. The virus movement was also dependent on NA. Virus movement mediated by HA and NA resulted in a three to four-fold increase in virus internalisation by cultured cells. We concluded that cooperation of HA and NA moves IAV particles on a cell surface and enhances virus infection of host cells.

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Influenza virus hemagglutinin (HA) is a determinant of virus infectivity. Therefore, it is important to determine whether HA of a new influenza virus, which can potentially cause pandemics, is functional against human cells. The novel imaging technique reported here allows rapid analysis of HA function by visualizing viral fusion inside cells. This imaging was designed to detect fusion changing the spectrum of the fluorescencelabeled virus. Using this imaging, we detected the fusion between a virus and a very small endosome that could not be detected previously, indicating that the imaging allows highly sensitive detection of viral fusion.

Influenza virus hemagglutinin (HA) has three highly conserved acylation sites close to the carboxyl terminus of the HA2 subunit, one in the transmembrane domain and two in the cytoplasmic domain. Each site is modified by palmitic acid through a thioester linkage to cysteine. To elucidate the biological significance of HA acylation, the acylation sites of HA of influenza virus strain A/USSR/77 (H1N1) were changed by site-directed mutagenesis, and the membrane fusion activity of mutant HAs lacking the acylation site(s) was examined quantitatively using transfer assays of lipid (R18) and aqueous (calcein) dyes. Lipid mixing, so-called hemifusion, activity was not affected by deacylation, whereas transfer of aqueous dye, so-called fusion pore formation, was dramatically restricted. When the fusion reaction was induced by a lower pH than the optimal one, calcein transfer with the mutant HAs was improved, but simultaneously a considerable calcein leakage into the medium was observed. From these results, we conclude that the palmitic acids on the H1 subtype HA facilitate the transition from hemifusion to fusion pore formation.The influenza virus particle attaches to the host cell and is internalized into the cell by receptor-mediated endocytosis. After entry, the virus membrane fuses to the endosomal membrane by acidification of the endosome, resulting in the transfer of the viral ribonucleoprotein into the cytoplasm. The attachment and membrane fusion are mediated by influenza virus hemagglutinin (HA) (11,24). HA is a homotrimer, and each monomer comprises an ectodomain with about 510 amino acid residues, a transmembrane domain with 27 residues, and a cytoplasmic domain with 10 to 11 residues. The HA monomer is synthesized as a single polypeptide chain and cleaved into two subunits, HA1 and HA2, by proteolytic enzymes after virus budding or during intracellular transport.The HA1 and HA2 subunits are functionally specialized. HA1 carries receptor-binding activity, and HA2 mediates membrane fusion (4, 24). The membrane fusion process can be divided into three steps: lipid mixing between the outer lipid monolayers of the viral and endosomal membranes (hemifusion), aqueous pore formation by connecting the two inner lipid monolayers, and pore dilation (8). The ectodomain of HA2 is thought to mediate hemifusion, and the transmembrane and cytoplasmic domains are thought to play an important role in pore formation (10,12,17). Three cysteine residues in the C-terminal region of HA2 are highly conserved between various subtypes of HA. These residues are posttranslationally modified with palmitic acids through thioester bonds, and these palmitoyl chains bind the cytoplasmic domain to the inner surface of the viral membrane (19,20,23,26). The strict conservation of the cysteine residues implies an important role for the acyl chains in the virus life cycle. However, the role of the acyl chains remains unclear.It remains a matter of debate whether the palmitylation of HA2 is involved in membrane fusion. To examine this subject, man...

BackgroundHelicobacter pylori infection is strongly associated with gastric cancer occurrence. However, it is unclear whether eradication therapy reduces the risk of gastric cancer occurrence. We evaluated whether H. pylori eradication reduces the risk of primary gastric cancer by using both risk ratio (RR) and risk difference (RD).MethodsSearches of PubMed, EMBASE, Google scholar, the Cochrane Library, and the Japan Medical Abstracts Society as well as those registered in databases of the Cochrane Central Register of Controlled Trials, metaRegister of Controlled Trials, ClinicalTrials.gov, controlled-trials.com, UMIN-CTR, JMACCT-CTR, and JAPIC-CTI between January 1965 and March 2017, supplemented with manual screening. Randomized controlled trials (RCTs) in which eradication therapy were implemented for the interventional group but not for the control group, and assessed the subsequent occurrence of primary gastric cancer as the main outcome. Two authors independently reviewed articles and extracted data. Integrated results for all data were presented as RR and RD.ResultsSeven studies met inclusion criteria. The reductions in risk of primary gastric cancer occurrence in terms of overall RR and RD were 0.67 (95% CI: 0.48 to 0.95) and -0.00 ([95% CI: -0.01 to 0.00]; number needed to treat: 125.5 [95% CI: 70.0 to 800.9]), respectively.ConclusionsThe effectiveness of H. pylori eradication therapy in suppressing the occurrence of primary gastric cancer was significant and comparable to that of previous studies in terms of the estimated RR. However, the estimated RD was slight and not statistically significant.