scholarly journals Conformational Occlusion of Blockade Antibody Epitopes, a Novel Mechanism of GII.4 Human Norovirus Immune Evasion

mSphere ◽  
2018 ◽  
Vol 3 (1) ◽  
Author(s):  
Lisa C. Lindesmith ◽  
Michael L. Mallory ◽  
Kari Debbink ◽  
Eric F. Donaldson ◽  
Paul D. Brewer-Jensen ◽  
...  
Keyword(s):  
Immune Evasion ◽  
Particle Dynamics ◽  
Human Norovirus ◽  
Viral Pathogens ◽  
Virus Like Particles ◽  
Antibody Epitope ◽  
Binding Residues ◽  
Additional Support ◽  
Key Residues ◽  
Antibody Epitopes

In this study, we use norovirus virus-like particles to identify key residues of a conserved GII.4 blockade antibody epitope. Further, we identify an additional GII.4 blockade antibody epitope to be occluded, with antibody access governed by temperature and particle dynamics. These findings provide additional support for particle conformation-based presentation of binding residues mediated by a particle “breathing core.” Together, these data suggest that limiting antibody access to blockade antibody epitopes may be a frequent mechanism of immune evasion for GII.4 human noroviruses. Mapping blockade antibody epitopes, the interaction between adjacent epitopes on the particle, and the breathing core that mediates antibody access to epitopes provides greater mechanistic understanding of epitope camouflage strategies utilized by human viral pathogens to evade immunity.

scholarly journals Immunogenicity of HIV-1-Based Virus-Like Particles with Increased Incorporation and Stability of Membrane-Bound Env

Vaccines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 239
Author(s):  
Christopher A. Gonelli ◽  
Hannah A. D. King ◽  
Charlene Mackenzie ◽  
Secondo Sonza ◽  
Rob J. Center ◽  
...  
Keyword(s):  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Neutralization Activity ◽  
Virus Like Particles ◽  
Antibody Isotypes ◽  
Immunodeficiency Virus ◽  
Proline Substitution ◽  
Membrane Bound ◽  
Antibody Epitopes ◽  
Hiv 1

An optimal prophylactic vaccine to prevent human immunodeficiency virus (HIV-1) transmission should elicit protective antibody responses against the HIV-1 envelope glycoprotein (Env). Replication-incompetent HIV-1 virus-like particles (VLPs) offer the opportunity to present virion-associated Env with a native-like structure during vaccination that closely resembles that encountered on infectious virus. Here, we optimized the incorporation of Env into previously designed mature-form VLPs (mVLPs) and assessed their immunogenicity in mice. The incorporation of Env into mVLPs was increased by replacing the Env transmembrane and cytoplasmic tail domains with those of influenza haemagglutinin (HA-TMCT). Furthermore, Env was stabilized on the VLP surface by introducing an interchain disulfide and proline substitution (SOSIP) mutations typically employed to stabilize soluble Env trimers. The resulting mVLPs efficiently presented neutralizing antibody epitopes while minimizing exposure of non-neutralizing antibody sites. Vaccination of mice with mVLPs elicited a broader range of Env-specific antibody isotypes than Env presented on immature VLPs or extracellular vesicles. The mVLPs bearing HA-TMCT-modified Env consistently induced anti-Env antibody responses that mediated modest neutralization activity. These mVLPs are potentially useful immunogens for eliciting neutralizing antibody responses that target native Env epitopes on infectious HIV-1 virions.

scholarly journals Attach Me If You Can: Murine Norovirus Binds to Commensal Bacteria and Fungi

Viruses ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 759 ◽  
Author(s):  
Jasmine L. Madrigal ◽  
Sutonuka Bhar ◽  
Samantha Hackett ◽  
Haley Engelken ◽  
Ross Joseph ◽  
...  
Keyword(s):  
Incubation Temperature ◽  
Growth Conditions ◽  
Fungal Species ◽  
Commensal Bacteria ◽  
Murine Norovirus ◽  
Human Norovirus ◽  
Viral Pathogens ◽  
Bacteria And Fungi ◽  
The Impact ◽  
Murine Noroviruses

The presence of commensal bacteria enhances both acute and persistent infection of murine noroviruses. For several enteric viral pathogens, mechanisms by which these bacteria enhance infection involve direct interactions between the virus and bacteria. While it has been demonstrated that human noroviruses bind to a variety of commensal bacteria, it is not known if this is also true for murine noroviruses. The goal of this study was to characterize interactions between murine noroviruses and commensal bacteria and determine the impact of bacterial growth conditions, incubation temperature and time, on murine norovirus attachment to microbes that comprise the mammalian microbiome. We show that murine noroviruses bind directly to commensal bacteria and show similar patterns of attachment as human norovirus VLPs examined under the same conditions. Furthermore, while binding levels are not impacted by the growth phase of the bacteria, they do change with time and incubation temperature. We also found that murine norovirus can bind to a commensal fungal species, Candida albicans.

scholarly journals Heterologous expression of human norovirus GII.4 VP1 leads to assembly of T=4 virus-like particles

2019 ◽  
Vol 168 ◽  
pp. 175-182 ◽  
Author(s):  
Jessica M. Devant ◽  
Götz Hofhaus ◽  
David Bhella ◽  
Grant S. Hansman
Keyword(s):  
Heterologous Expression ◽  
Human Norovirus ◽  
Virus Like Particles ◽  
Norovirus Gii

scholarly journals Emergence of Novel Human Norovirus GII.17 Strains Correlates With Changes in Blockade Antibody Epitopes

2017 ◽  
Vol 216 (10) ◽  
pp. 1227-1234 ◽  
Author(s):  
Lisa C Lindesmith ◽  
Jacob F Kocher ◽  
Eric F Donaldson ◽  
Kari Debbink ◽  
Michael L Mallory ◽  
...  
Keyword(s):  
Human Norovirus ◽  
Norovirus Gii ◽  
Antibody Epitopes

scholarly journals Identification of an immunodominant functional domain on human CD36 antigen using human-mouse chimaeric proteins and homologue-replacement mutagenesis

1995 ◽  
Vol 305 (1) ◽  
pp. 221-224 ◽  
Author(s):  
L Daviet ◽  
R Buckland ◽  
M D Puente Navazo ◽  
J L McGregor
Keyword(s):  
Amino Acids ◽  
Monoclonal Antibody ◽  
Monoclonal Antibodies ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Functional Domain ◽  
Oxidized Low Density Lipoprotein ◽  
Key Residues ◽  
Antibody Epitopes ◽  
Human And Mouse

The human CD36 antigen is a multifunctional membrane glycoprotein that acts as a receptor for thrombospondin, malaria-infected erythrocytes and oxidized low-density lipoprotein, as well as being implicated in the recognition of apoptotic neutrophils by macrophages. OKM5 and other anti-CD36 monoclonal antibodies have been shown to inhibit these CD36 adhesive functions, suggesting that the monoclonal-antibody epitopes and the domains that mediate these events are closely related. Analysis of a series of chimaeric exchanges between human and mouse CD36 shows that six anti-CD36 monoclonal antibodies (OKM5, FA6-152, L103, 5F1, SM phi and 10/5) recognize epitopes within the domain comprising amino acids 155-183. A seventh monoclonal antibody (13/10) binds to another domain that spans amino acids 30-76. Homologue-replacement mutagenesis performed within the human 155-183 immunodominant sequence identifies key residues for the binding of three functional monoclonal antibodies (OKM5, FA6-152 and L103). The fact that antibodies directed against the 155-183 domain can inhibit adhesion suggests that this domain is directly involved in CD36-ligand binding.

scholarly journals Antiviral Activity of Gold/Copper Sulfide Core/Shell Nanoparticles against Human Norovirus Virus-Like Particles

PLoS ONE ◽  
2015 ◽  
Vol 10 (10) ◽  
pp. e0141050 ◽  
Author(s):  
Jessica Jenkins Broglie ◽  
Brittny Alston ◽  
Chang Yang ◽  
Lun Ma ◽  
Audrey F. Adcock ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Copper Sulfide ◽  
Core Shell ◽  
Human Norovirus ◽  
Shell Nanoparticles ◽  
Virus Like Particles ◽  
Core Shell Nanoparticles

scholarly journals KILLER PHENOMENON IN USTILAGO MAYDIS: THE ORGANIZATION OF THE VIRAL GENOME

Genetics ◽  
1978 ◽  
Vol 88 (2) ◽  
pp. 267-276
Author(s):  
Y Koltin ◽  
J S Kandel
Keyword(s):  
Viral Genome ◽  
Ustilago Maydis ◽  
Double Stranded Rna ◽  
Virus Like Particles ◽  
Killer Strain ◽  
Additional Support ◽  
Killer Protein ◽  
Coding Capacity

ABSTRACT The double-stranded RNA content, the production of inactive killer protein, and the presence of virus-like particles were examined in induced nonkiller mutants and nonkiller progeny from a cross between a killer strain and a sensitive strain. A correlation between the loss of the 0.7 × 106 daltons dsRNA of the Ustilago maydis P6 virus and the lack of synthesis of the killer protein was established. In vitro and in vivo complementation between nonkiller strains provide additional support for the suggestion that the 0.7 × 106 daltons dsRNA is related to the killer function. The coding capacity of the various species of dsRNA is discussed in relation to their possible function.

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