scholarly journals Conformational modulation of influenza virus hemagglutinin: characterization and in vivo efficacy of monomeric form

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Jong Hyeon Seok ◽  
Jeongwon Kim ◽  
Dan Bi Lee ◽  
Ki Joon Cho ◽  
Ji-Hye Lee ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Monomeric Form ◽  
In Vivo Efficacy ◽  
Influenza Virus Hemagglutinin

scholarly journals Disulfide bond formation during the folding of influenza virus hemagglutinin.

1992 ◽  
Vol 118 (2) ◽  
pp. 227-244 ◽  
Author(s):  
M S Segal ◽  
J M Bye ◽  
J F Sambrook ◽  
M J Gething
Keyword(s):  
Influenza Virus ◽  
Disulfide Bonds ◽  
Intracellular Transport ◽  
Cellular Protein ◽  
Cysteine Residues ◽  
Mutant Proteins ◽  
Influenza Virus Hemagglutinin ◽  
Stalk Domain ◽  
Do So

To study the importance of individual sulfhydryl residues during the folding and assembly in vivo of influenza virus hemagglutinin (HA), we have constructed and expressed a series of mutant HA proteins in which cysteines involved in three disulfide bonds have been substituted by serine residues. Investigations of the structure and intracellular transport of the mutant proteins indicate that (a) cysteine residues in the ectodomain are essential both for efficient folding of HA and for stabilization of the folded molecule; (b) cysteine residues in the globular portion of the ectodomain are likely to form native disulfide bonds rapidly and directly, without involvement of intermediate, nonnative linkages; and (c) cysteine residues in the stalk portion of the ectodomain also appear not to form intermediate disulfide bonds, even though they have the opportunity to do so, being separated from their correct partners by hundreds of amino acids including two or more other sulfhydryl residues. We propose a role for the cellular protein BiP in shielding the cysteine residues of the stalk domain during the folding process, thus preventing them from forming intermediate, nonnative disulfide bonds.

scholarly journals Translocation in yeast and mammalian cells: not all signal sequences are functionally equivalent.

1987 ◽  
Vol 105 (6) ◽  
pp. 2905-2914 ◽  
Author(s):  
P Bird ◽  
M J Gething ◽  
J Sambrook
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Endoplasmic Reticulum ◽  
Influenza Virus ◽  
Signal Peptide ◽  
Mammalian Cells ◽  
Signal Sequence ◽  
Carboxypeptidase Y ◽  
Influenza Virus Hemagglutinin

In Saccharomyces cerevisiae, nascent carboxypeptidase Y (CPY) is directed into the endoplasmic reticulum by an NH2-terminal signal peptide that is removed before the glycosylated protein is transported to the vacuole. In this paper, we show that this signal peptide does not function in mammalian cells: CPY expressed in COS-1 cells is not glycosylated, does not associate with membranes, and retains its signal peptide. In a mammalian cell-free protein-synthesizing system, CPY is not translocated into microsomes. However, if the CPY signal is either mutated to increase its hydrophobicity or replaced with that of influenza virus hemagglutinin, the resulting precursors are efficiently translocated both in vivo and in vitro. The implications of these results for models of signal sequence function are discussed.

scholarly journals Complement Component C1q Enhances the Biological Activity of Influenza Virus Hemagglutinin-Specific Antibodies Depending on Their Fine Antigen Specificity and Heavy-Chain Isotype

2002 ◽  
Vol 76 (3) ◽  
pp. 1369-1378 ◽  
Author(s):  
Jing Qi Feng ◽  
Krystyna Mozdzanowska ◽  
Walter Gerhard
Keyword(s):  
Influenza Virus ◽  
Heavy Chain ◽  
Primary Response ◽  
Scid Mice ◽  
Complement Component ◽  
Heat Inactivation ◽  
Antigen Specificity ◽  
Influenza Virus Hemagglutinin

ABSTRACT We have previously observed that selected influenza virus hemagglutinin (HA)-specific monoclonal antibodies (MAbs) with poor virus-neutralizing (VN) activity in vitro exhibited greatly enhanced VN activity in vivo after administration to SCID mice. The same Abs displayed improved VN activity also when tested in vitro in the presence of noninactivated serum from SCID mice. To identify Ab-dependent properties and serum components that contributed to enhancement of Ab activity, we screened a large panel of HA-specific MAbs for hemagglutination inhibition (HI) in the presence of noninactivated serum from naive mice (NMS). We found that HI activity was enhanced by NMS depending on the Ab’s fine specificity (antigenic region Cb/E > Ca/A,D > Sa,Sb/B), its heavy-chain isotype (immunoglobulin G2 [IgG2] > IgG3; IgG1 and IgM negative), and to some extent also on its derivation (primary response > memory response). On average, the HI activity of Cb/E-specific MAbs of the IgG2 isotype isolated from the primary response was enhanced by 20-fold. VN activity was enhanced significantly but less strongly than HI activity. Enhancement (i) was destroyed by heat inactivation (30 min, 56°C); (ii) did not require C3, the central complement component; (iii) was abolished by treatment of serum with anti-C1q; and (iv) could be reproduced with purified C1q, the binding moiety of C1, the first complement component. We believe that this is the first description of a direct C1q-mediated enhancement of antiviral Ab activities.

1-Acyl-3-cyclooctylguanidines

1980 ◽  
Vol 45 (5) ◽  
pp. 1595-1600 ◽  
Author(s):  
Jaroslav Sluka ◽  
František Šmejkal ◽  
Zdeněk Buděšínský
Keyword(s):  
Influenza Virus ◽  
Herpes Simplex ◽  
Methyl Esters ◽  
Antiviral Effect ◽  
Influenza Virus A

On recation of cyclooctylamine with the sulfate of S-methylisothiourea cyclooctylguanidine was formed which was acylated with the methyl esters of 5-halogeno- and 3,5-dihalogeno-2-alkoxybenzoic acids. The 1-acyl-3-cyclooctylguanidine I-XVII formed were tested for their antiviral effect against the influenza virus A/NWS, A-PR8 and A2 Singapore, and further against the viruses NDV, herpes 2, vaccinia and WEE. In the in vivo test against the influenza virus A2 Singapore and herpes simplex 1-(5-bromo-2-dodecyloxybenzoyl)-3-cyclooctylguanidine is more active and less toxic than cyclooctylamine and 1-cyclooctylguanidine.

Sign in / Sign up

Export Citation Format

Share Document