Lipid Composition of the Viral Envelope of Three Strains of Influenza Virus—Not All Viruses Are Created Equal

Ivanova, Pavlina T.; Myers, David S.; Milne, Stephen; McClaren, Jennifer; Thomas, Paul G.; Brown, H. Alex

doi:10.1021/acsinfecdis.5b00040

Cited by 83 publications

(84 citation statements)

References 47 publications

(93 reference statements)

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“…Previous studies have shown that membranes enriched in cholesterol and phosphatidylethanolamines (PE) are resistant to surfactin permeabilization, while membranes containing phosphatidylcholines (PC) are more sensitive (28). The envelope of influenza A viruses have been reported to be enriched for both cholesterol and PE (29), providing support for this hypothesis. Unfortunately, the lipid content of the other viruses tested have not been determined, preventing direct comparison.…”

Section: Discussionmentioning

confidence: 94%

Peptidoglycan-Associated Cyclic Lipopeptide Disrupts Viral Infectivity

Johnson

Hage

Kalveram

et al. 2019

J Virol

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Enteric viruses exploit bacterial components, including lipopolysaccharides (LPS) and peptidoglycan (PG), to facilitate infection in humans. Because of their origin in the bat enteric system, we wondered if severe acute respiratory syndrome coronavirus (SARS-CoV) or Middle East respiratory syndrome CoV (MERS-CoV) also use bacterial components to modulate infectivity. To test this question, we incubated CoVs with LPS and PG and evaluated infectivity, finding no change following LPS treatment. However, PG from Bacillus subtilis reduced infection Ͼ10,000-fold, while PG from other bacterial species failed to recapitulate this. Treatment with an alcohol solvent transferred inhibitory activity to the wash, and mass spectrometry revealed surfactin, a cyclic lipopeptide antibiotic, as the inhibitory compound. This antibiotic had robust dose-and temperature-dependent inhibition of CoV infectivity. Mechanistic studies indicated that surfactin disrupts CoV virion integrity, and surfactin treatment of the virus inoculum ablated infection in vivo. Finally, similar cyclic lipopeptides had no effect on CoV infectivity, and the inhibitory effect of surfactin extended broadly to enveloped viruses, including influenza, Ebola, Zika, Nipah, chikungunya, Una, Mayaro, Dugbe, and Crimean-Congo hemorrhagic fever viruses. Overall, our results indicate that peptidoglycan-associated surfactin has broad viricidal activity and suggest that bacteria by-products may negatively modulate virus infection. IMPORTANCE In this article, we consider a role for bacteria in shaping coronavirus infection. Taking cues from studies of enteric viruses, we initially investigated how bacterial surface components might improve CoV infection. Instead, we found that peptidoglycan-associated surfactin is a potent viricidal compound that disrupts virion integrity with broad activity against enveloped viruses. Our results indicate that interactions with commensal bacterial may improve or disrupt viral infections, highlighting the importance of understanding these microbial interactions and their implications for viral pathogenesis and treatment.

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Section: Discussionmentioning

confidence: 94%

Peptidoglycan-Associated Cyclic Lipopeptide Disrupts Viral Infectivity

Johnson

Hage

Kalveram

et al. 2019

J Virol

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“…The system size along the Z axis was determined by adding 22.5 Å to the top and bottom of the protein, yielding an initial system size of ~250 x 250 x 380 Å 3 . Although biological viral membranes are asymmetric with different ratios of lipid types in the inner and outer leaflets [46][47] , in this study, the same mixed lipid ratio (DPPC:POPC:DPPE:POPE:DPPS:POPS:PSM:Chol=4:6:12:18:4:6:20:30) was used in both leaflets to represent a liquid-ordered viral membrane based on lipidomic data from influenza and HIV [46][47] ; see Table 3 for the full name of each lipid and their number in the system with the CP model 1. One should always visualize "step3_packing.pdb" (Figure 6B) to make sure that the protein is nicely packed by the lipid-like pseudo atoms and the system size in XY is reasonable.…”

Section: Membrane System Buildingmentioning

confidence: 99%

Developing a Fully-glycosylated Full-length SARS-CoV-2 Spike Protein Model in a Viral Membrane

Woo

Park

Choi

et al. 2020

Preprint

148

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This technical study describes all-atom modeling and simulation of a fully-glycosylated fulllength SARS-CoV-2 spike (S) protein in a viral membrane. First, starting from PDB:6VSB and 6VXX, full-length S protein structures were modeled using template-based modeling, de-novo protein structure prediction, and loop modeling techniques in GALAXY modeling suite. Then, using the recently-determined most occupied glycoforms, 22 N-glycans and 1 O-glycan of each monomer were modeled using Glycan Reader & Modeler in CHARMM-GUI. These fullyglycosylated full-length S protein model structures were assessed and further refined against the low-resolution data in their respective experimental maps using ISOLDE. We then used CHARMM-GUI Membrane Builder to place the S proteins in a viral membrane and performed all-atom molecular dynamics simulations. All structures are available in CHARMM-GUI COVID-19 Archive (http://www.charmm-gui.org/docs/archive/covid19), so researchers can use these models to carry out innovative and novel modeling and simulation research for the prevention and treatment of COVID-19.

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“…Previous studies have shown that membranes enriched in cholesterol and phosphatidylethanolamines (PE) are resistant to surfactin permeabilization, while membranes containing phosphatidylcholines (PC) are more sensitive (20). The envelope of Influenza A viruses have been reported to be enriched for both cholesterol and PE (21), providing support for this hypothesis. Unfortunately, the lipid content of the other viruses tested have not been determined, preventing direct comparison.…”

Section: Discussionmentioning

confidence: 85%

Peptidoglycan associated cyclic lipopeptide disrupts viral infectivity

Johnson

Hage

Kalveram

et al. 2019

Preprint

View full text Add to dashboard Cite

1Enteric viruses exploit bacterial components including lipopolysaccharides (LPS) and 2 peptidoglycan (PG) to facilitate infection in humans. With origins in the bat enteric system, we 3 wondered if severe acute respiratory syndrome-coronavirus (SARS-CoV) or Middle East 4 respiratory syndrome-CoV (MERS-CoV) also use bacterial components to modulate infectivity. 5To test this question, we incubated CoVs with LPS and PG and evaluated infectivity finding no 6 change following LPS treatment. However, PG from B. subtilis reduced infection >10,000-fold 7 while PG from other bacterial species failed to recapitulate this. Treatment with an alcohol 8 solvent transferred inhibitory activity to the wash and mass spectrometry revealed surfactin, a 9 cyclic lipopeptide antibiotic, as the inhibitory compound. This antibiotic had robust dose-and 1 0 temperature-dependent inhibition of CoV infectivity. Mechanistic studies indicated that surfactin 1 1 disrupts CoV virion integrity and surfactin treatment of the virus inoculum ablated infection in 1 2 vivo. Finally, similar cyclic lipopeptides had no effect on CoV infectivity and the inhibitory effect

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Lipid Composition of the Viral Envelope of Three Strains of Influenza Virus—Not All Viruses Are Created Equal

Cited by 83 publications

References 47 publications

Peptidoglycan-Associated Cyclic Lipopeptide Disrupts Viral Infectivity

Peptidoglycan-Associated Cyclic Lipopeptide Disrupts Viral Infectivity

Developing a Fully-glycosylated Full-length SARS-CoV-2 Spike Protein Model in a Viral Membrane

Peptidoglycan associated cyclic lipopeptide disrupts viral infectivity

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