Inhibition of Sendai virus fusion with phospholipid vesicles and human erythrocyte membranes by hydrophobic peptides

Journal Article · Sat Jun 01 04:00:00 EDT 1991 · Virology; (USA)

DOI:https://doi.org/10.1016/0042-6822(91)90610-N· OSTI ID:5761537

Kelsey, D R; Flanagan, T D; Young, J E; Yeagle, P L ^[1]

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1. State Univ. of New York, Buffalo (USA)

Hydrophobic di- and tripeptides which are capable of inhibiting enveloped virus infection of cells are also capable of inhibiting at least three different types of membrane fusion events. Large unilamellar vesicles (LUV) of N-methyl dioleoylphosphatidylethanolamine (N-methyl DOPE), containing encapsulated 1-aminonaphthalene-3,6,8-trisulfonic acid (ANTS) and/or p-xylene bis(pyridinium bromide) (DPX), were formed by extrusion. Vesicle fusion and leakage were then monitored with the ANTS/DPX fluorescence assay. Sendai virus fusion with lipid vesicles and Sendai virus fusion with human erythrocyte membranes were measured by following the relief of fluorescence quenching of virus labeled with octadecylrhodamine B chloride (R18). This study found that the effectiveness of the peptides carbobenzoxy-L-Phe-L-Phe (Z-L-Phe-L-Phe), Z-L-Phe, Z-D-Phe, and Z-Gly-L-Phe-L-Phe in inhibiting N-methyl DOPE LUV fusion or fusion of virus with N-methyl DOPE LUV also paralleled their reported ability to block viral infectivity. Furthermore, Z-D-Phe-L-PheGly and Z-Gly-L-Phe inhibited Sendai virus fusion with human erythrocyte membranes with the same relative potency with which they inhibited vesicle-vesicle and virus-vesicle fusion. The evidence suggests a mechanism by which these peptides exert their inhibition of plaque formation by enveloped viruses. This class of inhibitors apparently acts by inhibiting fusion of the viral envelope with the target cell membrane, thereby preventing viral infection. The physical pathway by which these peptides inhibit membrane fusion was investigated. {sup 31}P nuclear magnetic resonance (NMR) of proposed intermediates in the pathway for membrane fusion in LUV revealed that the potent fusion inhibitor Z-D-Phe-L-PheGly selectively altered the structure (or dynamics) of the hypothesized fusion intermediates and that the poor inhibitor Z-Gly-L-Phe did not.

• OSTI ID: 5761537
• Journal Information: Virology; (USA), Journal Name: Virology; (USA) Vol. 182:2; ISSN VIRLA; ISSN 0042-6822
• Country of Publication: United States
• Language: English

Related Subjects

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550901 -- Pathology-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMALS
BIOLOGICAL MATERIALS
BIOLOGICAL PATHWAYS
BLOOD
BLOOD CELLS
BODY FLUIDS
CELL CONSTITUENTS
CELL MEMBRANES
DISEASES
ERYTHROCYTES
ESTERS
FLUORESCENCE
IN VITRO
INFECTIOUS DISEASES
INFECTIVITY
INHIBITION
ISOTOPE APPLICATIONS
ISOTOPES
LIGHT NUCLEI
LIPIDS
LUMINESCENCE
MAGNETIC RESONANCE
MAMMALS
MAN
MATERIALS
MEMBRANES
MICROORGANISMS
NUCLEAR MAGNETIC RESONANCE
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
PARASITES
PEPTIDES
PHOSPHOLIPIDS
PHOSPHORUS 31
PHOSPHORUS ISOTOPES
PRIMATES
PROTEINS
RESONANCE
SOLUBILITY
STABLE ISOTOPES
STRUCTURE-ACTIVITY RELATIONSHIPS
TRACER TECHNIQUES
VERTEBRATES
VIRAL DISEASES
VIRUSES