ph-Dependent hydrophobicity profile of hemagglutinin of influenza virus and its possible relevance in virus fusion

1992 ◽  
Vol 12 (5) ◽  
pp. 397-406 ◽  
Author(s):  
Thomas Korte ◽  
Kai Ludwig ◽  
Andreas Herrmann
Keyword(s):  
Influenza Virus ◽  
Biological Membranes ◽  
Neutral Ph ◽  
Virus Fusion ◽  
N Terminus ◽  
Ph Dependent ◽  
Terminal Site ◽  
Hydrophobicity Profile

The hydropathy profile of hemagglutinin (HA) subunits HA1 and HA2 of influenza virus X31 and A/PR 8/34 is analyzed at different pH. At neutral pH (7.4) pronounced hydrophobic sequences of HA correspond to the N-terminus and the transmembrane spanning sequence of HA2. At pH 5.0 where influenza virus is known to fuse with biological membranes several hydrophobic sequences in the ectodomain exist which are comparable in both the hydrophobicity and length of the N-terminus of HA2. It is suggested that these hydrophobic stretches are important for the fusion complex, in addition to the N-terminal site of HA2.

scholarly journals Role of Hemagglutinin Surface Density in the Initial Stages of Influenza Virus Fusion: Lack of Evidence for Cooperativity

2000 ◽  
Vol 74 (6) ◽  
pp. 2714-2720 ◽  
Author(s):  
Susanne Günther-Ausborn ◽  
Pieter Schoen ◽  
Ingrid Bartoldus ◽  
Jan Wilschut ◽  
Toon Stegmann
Keyword(s):  
Influenza Virus ◽  
Surface Density ◽  
Initial Rate ◽  
Fusion Activity ◽  
Cooperative Action ◽  
Lipid Ratio ◽  
Virus Fusion ◽  
Influenza Virus Hemagglutinin ◽  
Optimal Fusion

ABSTRACT Membrane fusion mediated by influenza virus hemagglutinin (HA) is believed to proceed via the cooperative action of multiple HA trimers. To determine the minimal number of HA trimers required to trigger fusion, and to assess the importance of cooperativity between these HA trimers, we have generated virosomes containing coreconstituted HAs derived from two strains of virus with different pH dependencies for fusion, X-47 (optimal fusion at pH 5.1; threshold at pH 5.6) and A/Shangdong (optimal fusion at pH 5.6; threshold at pH 6.0), and measured fusion of these virosomes with erythrocyte ghosts by a fluorescence lipid mixing assay. Virosomes with different X-47-to-A/Shangdong HA ratios, at a constant HA-to-lipid ratio, showed comparable ghost-binding activities, and the low-pH-induced conformational change of A/Shangdong HA did not affect the fusion activity of X-47 HA. The initial rate of fusion of these virosomes at pH 5.7 increased directly proportional to the surface density of A/Shangdong HA, and a single A/Shangdong trimer per virosome appeared to suffice to induce fusion. The reciprocal of the lag time before the onset of fusion was directly proportional to the surface density of fusion-competent HA. These results support the notion that there is no cooperativity between HA trimers during influenza virus fusion.

Estimation by radiation inactivation of the size of functional units governing Sendai and influenza virus fusion

Biochemistry ◽  
1987 ◽  
Vol 26 (19) ◽  
pp. 6223-6227 ◽  
Author(s):  
Keiko Bundo-Morita ◽  
Suzanne Gibson ◽  
John Lenard
Keyword(s):  
Influenza Virus ◽  
Radiation Inactivation ◽  
Virus Fusion ◽  
Functional Units

scholarly journals Low-pH-Dependent Fusion of Sindbis Virus with Receptor-Free Cholesterol- and Sphingolipid-Containing Liposomes

1999 ◽  
Vol 73 (10) ◽  
pp. 8476-8484 ◽  
Author(s):  
Jolanda M. Smit ◽  
Robert Bittman ◽  
Jan Wilschut
Keyword(s):  
Sindbis Virus ◽  
Core Protein ◽  
Fusion Reaction ◽  
Low Ph ◽  
Viral Envelope ◽  
Cell Entry ◽  
Receptor Interaction ◽  
Neutral Ph ◽  
Virus Fusion ◽  
Entry Mechanism

ABSTRACT There is controversy as to whether the cell entry mechanism of Sindbis virus (SIN) involves direct fusion of the viral envelope with the plasma membrane at neutral pH or uptake by receptor-mediated endocytosis and subsequent low-pH-induced fusion from within acidic endosomes. Here, we studied the membrane fusion activity of SIN in a liposomal model system. Fusion was followed fluorometrically by monitoring the dilution of pyrene-labeled lipids from biosynthetically labeled virus into unlabeled liposomes or from labeled liposomes into unlabeled virus. Fusion was also assessed on the basis of degradation of the viral core protein by trypsin encapsulated in the liposomes. SIN fused efficiently with receptor-free liposomes, consisting of phospholipids and cholesterol, indicating that receptor interaction is not a mechanistic requirement for fusion of the virus. Fusion was optimal at pH 5.0, with a threshold at pH 6.0, and undetectable at neutral pH, supporting a cell entry mechanism of SIN involving fusion from within acidic endosomes. Under optimal conditions, 60 to 85% of the virus fused, depending on the assay used, corresponding to all of the virus bound to the liposomes as assessed in a direct binding assay. Preincubation of the virus alone at pH 5.0 resulted in a rapid loss of fusion capacity. Fusion of SIN required the presence of both cholesterol and sphingolipid in the target liposomes, cholesterol being primarily involved in low-pH-induced virus-liposome binding and the sphingolipid catalyzing the fusion process itself. Under low-pH conditions, the E2/E1 heterodimeric envelope glycoprotein of the virus dissociated, with formation of a trypsin-resistant E1 homotrimer, which kinetically preceded the fusion reaction, thus suggesting that the E1 trimer represents the fusion-active conformation of the viral spike.

Stochastic Model of Influenza Virus Fusion

2004 ◽  
pp. 411-420
Author(s):  
Susanne Schreiber ◽  
Kai Ludwig ◽  
Hermann-Georg Holzhütter ◽  
Andreas Herrmann
Keyword(s):  
Influenza Virus ◽  
Stochastic Model ◽  
Virus Fusion

scholarly journals PB1-mediated virulence attenuation of H5N1 influenza virus in mice is associated with PB2

2011 ◽  
Vol 92 (6) ◽  
pp. 1435-1444 ◽  
Author(s):  
Jing Li ◽  
Yongqiang Li ◽  
Yi Hu ◽  
Guohui Chang ◽  
Wei Sun ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Recombinant Virus ◽  
Influenza Viruses ◽  
H5n1 Influenza Virus ◽  
Wild Type ◽  
Small Plaque ◽  
Large Plaque ◽  
H5n1 Influenza ◽  
Virulence Attenuation ◽  
N Terminus

H5N1 avian influenza viruses demonstrate different phenotypes, such as pathogenicity after one or serial passages in mammalian hosts or cells. To establish the molecular basis of these phenotypes, we cloned isolates from the lungs of mice infected with human A/Vietnam/1194/2004 (H5N1) influenza virus. Large-plaque isolates were less pathogenic to mice than small-plaque isolates. Genome sequencing revealed that the small-plaque and large-plaque isolates differed in several amino acids. In order to assess their effects on pathogenicity in mice, two amino acid changes common to attenuated isolates, one in PB2 (I63T) and the other in PB1 (T677M), were inserted into a wild-type recombinant virus construct. The PB2 (I63T) or PB1 (T677M) mutations alone did not alter the phenotype of H5N1 virus, whereas recombinant virus with both mutations was less pathogenic than the wild-type recombinant virus. Furthermore, the PB1 (T677M) mutation showed a lower replication efficiency, although it had higher polymerase activity. The recombinant virus with the PB2 (63T) mutation replicated as well as the wild-type recombinant virus. These results suggest that the C terminus of PB1 of H5N1 influenza virus mediates virulence attenuation of H5N1 influenza virus in mice, associating with the N terminus of PB2. However, the role of the N terminus of PB2 in virulence attenuation in mice remains unclear.

HA1-2-fljB Vaccine Induces Immune Responses against Pandemic Swine-Origin H1N1 Influenza Virus in Mice

2016 ◽  
Vol 26 (6) ◽  
pp. 422-432 ◽  
Author(s):  
Xilong Kang ◽  
Yun Yang ◽  
Yang Jiao ◽  
Hongqin Song ◽  
Li Song ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza A ◽  
H1n1 Virus ◽  
Influenza Virus Infection ◽  
Candidate Vaccine ◽  
Major Barrier ◽  
Excellent Starting Point ◽  
Starting Point ◽  
Influenza A H1n1 ◽  
N Terminus

In 2009, a novel pandemic swine-origin influenza A (H1N1) virus caused a public emergency of international concern. Vaccination is the primary strategy for the control of influenza epidemics. However, the poor immunopotency of many vaccine antigens is a major barrier to the development of effective vaccines against influenza. Flagellin, a Toll-like receptor 5 (TLR5) ligand, has been used as an adjuvant to enhance the immunopotency of vaccines in preclinical studies. Here, we developed a recombinant candidate vaccine, HA1-2-fljB, in which the globular head of the hemagglutinin (HA) antigen (residues 62-284) from H1N1 virus was fused genetically to the N-terminus of <i>Salmonella typhimurium</i> &#xFB02;jB. The recombinant HA1-2-fljB protein was expressed efficiently in<i> Escherichia coli</i>, and the immunogenicity and protective efficacy of recombinant HA1-2-fljB were evaluated in a mouse model. Immunization with HA1-2-fljB elicited robust IgG antibodies and neutralizing antibodies and completely protected the mice against infection by swine-origin influenza A/swine/Jangsu/38/2010 (H1N1). These results suggest that HA antigen placed at the N-terminus of flagellin is also an excellent starting point for creating a fusion HA1-2-fljB protein as a candidate vaccine, and the recombinant HA1-2-fljB protein will contribute to the development of a more effective vaccine against swine-origin influenza virus infection.

scholarly journals Lysolipids Do Not Inhibit Influenza Virus Fusion by Interaction with Hemagglutinin

2002 ◽  
Vol 277 (23) ◽  
pp. 20461-20467 ◽  
Author(s):  
Bolormaa Baljinnyam ◽  
Britta Schroth-Diez ◽  
Thomas Korte ◽  
Andreas Herrmann
Keyword(s):  
Influenza Virus ◽  
Virus Fusion
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