Non-Enveloped Virus Entry: Structural Determinants and Mechanism of Functioning of a Viral Lytic Peptide

Bajaj, Saumya; Dey, Debajit; Bhukar, Rohan; Kumar, Mohit; Banerjee, Manidipa

doi:10.1016/j.jmb.2016.06.006

Cited by 24 publications

(23 citation statements)

References 68 publications

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“…However, a recent study has also examined the FHV γ-peptide using MD and experimental methods. 43 In that study γ 1 , the full-length γ-peptide and a construct peptide in which the 8 C-terminal residues of γ were fused to γ 1 (termed Δ385–399), were investigated to characterize their interactions with membranes. The Δ385–399 construct contained three Phe residues in the C-terminal region, which had been previously implicated to be critical for membrane disruption, 14 yet Δ385–399 was less effective in disrupting membranes than γ 1 or even a non-cleaving maturation defective mutant.…”

Section: Discussionmentioning

confidence: 99%

Influence of membrane composition on the binding and folding of a membrane lytic peptide from the non-enveloped flock house virus

Nangia

May

2017

Biochimica et Biophysica Acta (BBA) - Biomembranes

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Using a combination of coarse-grained and atomistic molecular dynamics simulations we have investigated the membrane binding and folding properties of the membrane lytic peptide of Flock House virus (FHV). FHV is an animal virus and an excellent model system for studying cell entry mechanisms in non-enveloped viruses. FHV undergoes a maturation event where the 44 C-terminal amino acids are cleaved from the major capsid protein, forming the membrane lytic (γ) peptides. Under acidic conditions, γ is released from the capsid interior allowing the peptides to bind and disrupt membranes. The first 21 N-terminal residues of γ, termed γ1, have been resolved in the FHV capsid structure and γ1 has been the subject of in vitro studies. γ1 is structurally dynamic as it adopts helical secondary structure inside the capsid and on membranes, but it is disordered in solution. In vitro studies have shown the binding free energies to POPC or POPG membranes are nearly equivalent, but binding to POPC is enthalpically driven, while POPG binding is entropically driven. Through coarse-grained and multiple microsecond all-atom simulations the membrane binding and folding properties of γ1 are investigated against homogeneous and heterogeneous bilayers to elucidate the dependence of the microenvironment on the structural properties of γ1. Our studies provide a rationale for the thermodynamic data and suggest binding of γ1 to POPG bilayers occurs in a disordered state, but γ1 must adopt a helical conformation when binding POPC bilayers.

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Section: Discussionmentioning

confidence: 99%

Influence of membrane composition on the binding and folding of a membrane lytic peptide from the non-enveloped flock house virus

Nangia

May

2017

Biochimica et Biophysica Acta (BBA) - Biomembranes

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“…However, the concurrent mutation on the N‐terminal side seems to decrease these properties slightly, especially the absorption rate, suggesting that this region could also be involved in viral binding. In the related genus alfanodavirus, the association with cell membranes, previous to viral release in cytoplasm, has been recently reported to be produced by both terminal sides of capsid proteins (Bajaj, Dey, Bhukar, Kumar, & Banerjee, ).…”

Section: Discussionmentioning

confidence: 99%

Amino acid changes in the capsid protein of a reassortant betanodavirus strain: Effect on viral replication in vitro and in vivo

Souto

Olveira

García-Rosado

et al. 2018

Journal of Fish Diseases

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Betanodavirus reassortant strains (RGNNV/SJNNV) isolated from Senegalese sole harbour an SJNNV capsid featuring several changes with respect to the SJNNV‐type strain, sharing three hallmark substitutions. Here, we have employed recombinant strains harbouring mutations in these positions (r20 and r20 + 247 + 270) and have demonstrated that the three substitutions affect different steps of the viral replication process. Adsorption ability and efficiency of viral attachment were only affected by substitutions in the C‐terminal side of the capsid. However, the concurrent mutation in the N‐terminal side seems to slightly decrease these properties, suggesting that this region could also be involved in viral binding. Differences in the intracellular and extracellular production of the mutant strains suggest that both the C‐terminal and N‐terminal regions of the capsid protein may be involved in the particle budding. Furthermore, viral replication in sole brain tissue of the mutant strains, and especially double‐ and triple‐mutant strains, is clearly delayed with respect to the wt strain. These data support previous findings indicating that the C‐terminal side plays a role in virulence because of a slower spread in the fish host brain and suggest that the concurrent participation of the N‐terminal side is also important for viral replication in vivo.

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“…At neutral pH the γ peptide is able to cause membrane disruption; while at low pH it is only able to alter its location relative to the capsid, but does not increase its membrane interacting ability . Surprisingly, thanks to a kinked structure and a tight alignment of the hydrophobic residues on one side of the peptide at low pH similar to influenza virus, FHV γ peptide shows localized perturbation of lipid arrangements with no proof of pore formation . While membrane destabilization requires the simple insertion of the fusion peptide into the outer leaflet of the lipid bilayer, leakage needs both a deeper insertion and an interaction between peptides inside the membrane.…”

Section: Membranotropic Peptidesmentioning

confidence: 99%

“…Non‐enveloped viruses exploit a different mechanism for entry because they lack a membrane which surrounds the protein capsid; as a consequence they require capsid‐dependent mechanisms for penetrating the cell membrane or for exiting from the endosome . The entry process is much less known and involves a series of triggers producing conformational and structural rearrangements which end in the exposure and/or release of lytic factors.…”

Section: Viral Entrymentioning

confidence: 99%

“…The N‐terminal 21 amino acids of the FHV γ peptide form an amphipathic α‐helix which is commonly referred to as γ1, while the γ peptide comprises also a C‐terminal region which is commonly considered to play a supporting role for the correct positioning of γ1. The γ peptide assumes a random coil conformation in solution, while it adopts a kinked helical conformation in model membranes; similarly to other membranotropic peptides also viral lytic factors seem to be able to adopt a membrane‐active conformation when interacting with the lipid bilayer . The γ1 peptide is able to spontaneously partition into lipid bilayers and increases the membrane permeability of liposomes; in particular, it mediates liposome lysis through the insertion only into the outer leaflet of the lipid bilayer, and locating parallel to the membrane surface, with the hydrophobic face of the helix packed against the membrane surface .…”

Section: Membranotropic Peptidesmentioning

confidence: 99%

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Membranotropic peptides mediating viral entry

et al. 2018

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The means used by enveloped viruses to bypass cellular membranes are well characterized; however, the mechanisms used by non‐enveloped viruses to deliver their genome inside the cell remain unresolved and poorly defined. The discovery of short, membrane interacting, amphipathic or hydrophobic sequences (known as membranotropic peptides) in both enveloped and non‐enveloped viruses suggests that these small peptides are strongly involved in breaching the host membrane and in the delivery of the viral genome into the host cell. Thus, in spite of noticeable differences in entry, this short stretches of membranotropic peptides are probably associated with similar entry‐related events. This review will uncover the intrinsic features of viral membranotropic peptides involved in viral entry of both naked viruses and the ones encircled with a biological membrane with the objective to better elucidate their different functional properties and possible applications in the biomedical field.

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Non-Enveloped Virus Entry: Structural Determinants and Mechanism of Functioning of a Viral Lytic Peptide

Cited by 24 publications

References 68 publications

Influence of membrane composition on the binding and folding of a membrane lytic peptide from the non-enveloped flock house virus

Influence of membrane composition on the binding and folding of a membrane lytic peptide from the non-enveloped flock house virus

Amino acid changes in the capsid protein of a reassortant betanodavirus strain: Effect on viral replication in vitro and in vivo

Membranotropic peptides mediating viral entry

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