Biophysical Characterization and Membrane Interaction of the Two Fusion Loops of Glycoprotein B from Herpes Simplex Type I Virus

Falanga, Annarita; Tarallo, Rossella; Vitiello, Giuseppe; Vitiello, Mariateresa; Perillo, E.; Cantisani, Marco; D’Errico, Gerardino; Galdiero, Massimiliano; Galdiero, Stefania

doi:10.1371/journal.pone.0032186

Cited by 38 publications

(35 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…(C) Ribbon representation of the best CYANA structure (i.e., the one with the lowest target function: n.1); 142 distance constraints (54 intraresidue, 62 short-, and 26 medium-range) and 42 angle constraints were incorporated in the final structure calculation. (40)(41)(42). Aromatic residue-containing peptides possess the unique ability to interact with the surface of bacterial cell membranes.…”

Section: Resultsmentioning

confidence: 99%

Structural Insights into and Activity Analysis of the Antimicrobial Peptide Myxinidin

Cantisani

Finamore

Mignogna

et al. 2014

Antimicrob Agents Chemother

Self Cite

View full text Add to dashboard Cite

eThe marine environment has been poorly explored in terms of potential new molecules possessing antibacterial activity. Antimicrobial peptides (AMPs) offer a new potential class of pharmaceuticals; however, further optimization is needed if AMPs are to find broad use as antibiotics. We focused our studies on a peptide derived from the epidermal mucus of hagfish (Myxine glutinosa L.), which was previously characterized and showed high antimicrobial activity against human and fish pathogens. In the present work, the activities of myxinidin peptide analogues were analyzed with the aim of widening the original spectrum of action of myxinidin by suitable changes in the peptide primary structure. The analysis of key residues by alanine scanning allowed for the design of novel peptides with increased activity. We identified the amino acids that are of the utmost importance for the observed antimicrobial activities against a set of pathogens comprising both Gram-negative and Gram-positive bacteria. Overall, optimized bactericidal potency was achieved by adding a tryptophan residue at the N terminus and by the simultaneous substitution of residues present in positions 3, 4, and 11 with arginine. These results indicate that the myxinidin analogues emerge as an attractive alternative for treating drug-resistant infectious diseases and provide key insights into a rational design for novel agents against these pathogens.

show abstract

Section: Resultsmentioning

confidence: 99%

Structural Insights into and Activity Analysis of the Antimicrobial Peptide Myxinidin

Cantisani

Finamore

Mignogna

et al. 2014

Antimicrob Agents Chemother

Self Cite

View full text Add to dashboard Cite

show abstract

“…We thus decided to verify the antibacterial activity of an analogue containing a tryptophan residue at the N terminus (44). Tryptophan residues have the unique property of being able to interact with the interfacial region of a membrane, thereby anchoring the peptide to the bilayer surface, and are very common in viral fusion peptides (45)(46)(47). The Trp residue has a strong membrane-disruptive activity, and this property endows Trp-containing peptides with the unique ability to interact with the surface of bacterial cell membranes.…”

Section: Discussionmentioning

confidence: 99%

Structure-Activity Relations of Myxinidin, an Antibacterial Peptide Derived from the Epidermal Mucus of Hagfish

Cantisani

Leone

Mignogna

et al. 2013

Antimicrob Agents Chemother

Self Cite

View full text Add to dashboard Cite

The structure-activity relations of myxinidin, a peptide derived from epidermal mucus of hagfish, Myxine glutinosa L., were investigated. Analysis of key residues allowed us to design new peptides with increased efficiency. Antimicrobial activity of native and modified peptides demonstrated the key role of uncharged residues in the sequence; the loss of these residues reduces almost entirely myxinidin antimicrobial activity, while insertion of arginine at charged and uncharged position increases antimicrobial activity compared with that of native myxinidin. Particularly, we designed a peptide capable of achieving a high inhibitory effect on bacterial growth. Experiments were conducted using both Gram-negative and Gram-positive bacteria. Nuclear magnetic resonance (NMR) studies showed that myxinidin is able to form an amphipathic ␣-helical structure at the N terminus and a random coil region at the C terminus.

show abstract

“…We showed approximately 90% inhibition of viral entry by cholesterol depletion. Since herpesvirus fusion may be influenced by the lipid composition of membranes (128,129), cholesterol depletion may also lead to a reduction in virus fusion. Accordingly, we cannot rule out gHgLmediated EBV basolateral entry by direct fusion of viral envelopes with cell membranes.…”

Section: Cd19mentioning

confidence: 99%

Epstein-Barr Virus Transcytosis through Polarized Oral Epithelial Cells

Tugizov

Herrera

Palefsky

2013

J Virol

View full text Add to dashboard Cite

Although Epstein-Barr virus (EBV) is an orally transmitted virus, viral transmission through the oropharyngeal mucosal epithelium is not well understood. In this study, we investigated how EBV traverses polarized human oral epithelial cells without causing productive infection. We found that EBV may be transcytosed through oral epithelial cells bidirectionally, from both the apical to the basolateral membranes and the basolateral to the apical membranes. Apical to basolateral EBV transcytosis was substantially reduced by amiloride, an inhibitor of macropinocytosis. Electron microscopy showed that virions were surrounded by apical surface protrusions and that virus was present in subapical vesicles. Inactivation of signaling molecules critical for macropinocytosis, including phosphatidylinositol 3-kinases, myosin light-chain kinase, Ras-related C3 botulinum toxin substrate 1, p21-activated kinase 1, ADP-ribosylation factor 6, and cell division control protein 42 homolog, led to significant reduction in EBV apical to basolateral transcytosis. In contrast, basolateral to apical EBV transcytosis was substantially reduced by nystatin, an inhibitor of caveolin-mediated virus entry. Caveolae were detected in the basolateral membranes of polarized human oral epithelial cells, and virions were detected in caveosome-like endosomes. Methyl ␤-cyclodextrin, an inhibitor of caveola formation, reduced EBV basolateral entry. EBV virions transcytosed in either direction were able to infect B lymphocytes. Together, these data show that EBV transmigrates across oral epithelial cells by (i) apical to basolateral transcytosis, potentially contributing to initial EBV penetration that leads to systemic infection, and (ii) basolateral to apical transcytosis, which may enable EBV secretion into saliva in EBV-infected individuals.

show abstract

Biophysical Characterization and Membrane Interaction of the Two Fusion Loops of Glycoprotein B from Herpes Simplex Type I Virus

Cited by 38 publications

References 67 publications

Structural Insights into and Activity Analysis of the Antimicrobial Peptide Myxinidin

Structural Insights into and Activity Analysis of the Antimicrobial Peptide Myxinidin

Structure-Activity Relations of Myxinidin, an Antibacterial Peptide Derived from the Epidermal Mucus of Hagfish

Epstein-Barr Virus Transcytosis through Polarized Oral Epithelial Cells

Contact Info

Product

Resources

About