Other search tools

About this data

The publication data currently available has been vetted by Vanderbilt faculty, staff, administrators and trainees. The data itself is retrieved directly from NCBI's PubMed and is automatically updated on a weekly basis to ensure accuracy and completeness.

If you have any questions or comments, please contact us.

Results: 1 to 10 of 11

Publication Record

Connections

A human antibody against Zika virus crosslinks the E protein to prevent infection.
Hasan SS, Miller A, Sapparapu G, Fernandez E, Klose T, Long F, Fokine A, Porta JC, Jiang W, Diamond MS, Crowe JE, Kuhn RJ, Rossmann MG
(2017) Nat Commun 8: 14722
MeSH Terms: Antibodies, Monoclonal, Antibodies, Neutralizing, Antibodies, Viral, Binding Sites, Cryoelectron Microscopy, HEK293 Cells, Humans, Models, Molecular, Protein Binding, Protein Domains, Protein Multimerization, Viral Structural Proteins, Zika Virus, Zika Virus Infection
Show Abstract · Added April 13, 2017
The recent Zika virus (ZIKV) epidemic has been linked to unusual and severe clinical manifestations including microcephaly in fetuses of infected pregnant women and Guillian-Barré syndrome in adults. Neutralizing antibodies present a possible therapeutic approach to prevent and control ZIKV infection. Here we present a 6.2 Å resolution three-dimensional cryo-electron microscopy (cryoEM) structure of an infectious ZIKV (strain H/PF/2013, French Polynesia) in complex with the Fab fragment of a highly therapeutic and neutralizing human monoclonal antibody, ZIKV-117. The antibody had been shown to prevent fetal infection and demise in mice. The structure shows that ZIKV-117 Fabs cross-link the monomers within the surface E glycoprotein dimers as well as between neighbouring dimers, thus preventing the reorganization of E protein monomers into fusogenic trimers in the acidic environment of endosomes.
0 Communities
1 Members
0 Resources
14 MeSH Terms
Both genome segments contribute to the pathogenicity of very virulent infectious bursal disease virus.
Escaffre O, Le Nouën C, Amelot M, Ambroggio X, Ogden KM, Guionie O, Toquin D, Müller H, Islam MR, Eterradossi N
(2013) J Virol 87: 2767-80
MeSH Terms: Amino Acid Sequence, Animals, Base Sequence, Birnaviridae Infections, Chick Embryo, Chickens, Infectious bursal disease virus, Molecular Dynamics Simulation, Poultry Diseases, Sequence Analysis, RNA, Spleen, Thymus Gland, Viral Structural Proteins
Show Abstract · Added April 26, 2017
Infectious bursal disease virus (IBDV) causes an economically significant disease of chickens worldwide. Very virulent IBDV (vvIBDV) strains have emerged and induce as much as 60% mortality. The molecular basis for vvIBDV pathogenicity is not understood, and the relative contributions of the two genome segments, A and B, to this phenomenon are not known. Isolate 94432 has been shown previously to be genetically related to vvIBDVs but exhibits atypical antigenicity and does not cause mortality. Here the full-length genome of 94432 was determined, and a reverse genetics system was established. The molecular clone was rescued and exhibited the same antigenicity and reduced pathogenicity as isolate 94432. Genetically modified viruses derived from 94432, whose vvIBDV consensus nucleotide sequence was restored in segment A and/or B, were produced, and their pathogenicity was assessed in specific-pathogen-free chickens. We found that a valine (position 321) that modifies the most exposed part of the capsid protein VP2 critically modified the antigenicity and partially reduced the pathogenicity of 94432. However, a threonine (position 276) located in the finger domain of the virus polymerase (VP1) contributed even more significantly to attenuation. This threonine is partially exposed in a hydrophobic groove on the VP1 surface, suggesting possible interactions between VP1 and another, as yet unidentified molecule at this amino acid position. The restored vvIBDV-like pathogenicity was associated with increased replication and lesions in the thymus and spleen. These results demonstrate that both genome segments influence vvIBDV pathogenicity and may provide new targets for the attenuation of vvIBDVs.
0 Communities
1 Members
0 Resources
13 MeSH Terms
An alphavirus replicon-based human metapneumovirus vaccine is immunogenic and protective in mice and cotton rats.
Mok H, Tollefson SJ, Podsiad AB, Shepherd BE, Polosukhin VV, Johnston RE, Williams JV, Crowe JE
(2008) J Virol 82: 11410-8
MeSH Terms: Administration, Intranasal, Animals, Antibodies, Viral, Cell Line, Encephalitis Virus, Venezuelan Equine, Immunoglobulin A, Immunoglobulin G, Lung, Macaca mulatta, Metapneumovirus, Mice, Mice, Inbred DBA, Mucous Membrane, Neutralization Tests, Paramyxoviridae Infections, Rats, Respiratory System, Sigmodontinae, Viral Structural Proteins, Viral Vaccines
Show Abstract · Added August 6, 2012
Human metapneumovirus (hMPV) is a recently discovered paramyxovirus that causes upper and lower respiratory tract infections in infants, the elderly, and immunocompromised individuals worldwide. Here, we developed Venezuelan equine encephalitis virus replicon particles (VRPs) encoding hMPV fusion (F) or attachment (G) glycoproteins and evaluated the immunogenicity and protective efficacy of these vaccine candidates in mice and cotton rats. VRPs encoding hMPV F protein, when administered intranasally, induced F-specific virus-neutralizing antibodies in serum and immunoglobulin A (IgA) antibodies in secretions at the respiratory mucosa. Challenge virus replication was reduced significantly in both the upper and lower respiratory tracts following intranasal hMPV challenge in these animals. However, vaccination with hMPV G protein VRPs did not induce neutralizing antibodies or protect animals from hMPV challenge. Close examination of the histopathology of the lungs of VRP-MPV F-vaccinated animals following hMPV challenge revealed no enhancement of inflammation or mucus production. Aberrant cytokine gene expression was not detected in these animals. Together, these results represent an important first step toward the use of VRPs encoding hMPV F proteins as a prophylactic vaccine for hMPV.
0 Communities
1 Members
0 Resources
20 MeSH Terms
Severe acute respiratory syndrome coronavirus group-specific open reading frames encode nonessential functions for replication in cell cultures and mice.
Yount B, Roberts RS, Sims AC, Deming D, Frieman MB, Sparks J, Denison MR, Davis N, Baric RS
(2005) J Virol 79: 14909-22
MeSH Terms: Animals, Coronavirus Infections, Mice, Open Reading Frames, SARS Virus, Viral Proteins, Viral Structural Proteins, Virus Replication
Show Abstract · Added February 19, 2015
SARS coronavirus (SARS-CoV) encodes several unique group-specific open reading frames (ORFs) relative to other known coronaviruses. To determine the significance of the SARS-CoV group-specific ORFs in virus replication in vitro and in mice, we systematically deleted five of the eight group-specific ORFs, ORF3a, OF3b, ORF6, ORF7a, and ORF7b, and characterized recombinant virus replication and gene expression in vitro. Deletion of the group-specific ORFs of SARS-CoV, either alone or in various combinations, did not dramatically influence replication efficiency in cell culture or in the levels of viral RNA synthesis. The greatest reduction in virus growth was noted following ORF3a deletion. SARS-CoV spike (S) glycoprotein does not encode a rough endoplasmic reticulum (rER)/Golgi retention signal, and it has been suggested that ORF3a interacts with and targets S glycoprotein retention in the rER/Golgi apparatus. Deletion of ORF3a did not alter subcellular localization of the S glycoprotein from distinct punctuate localization in the rER/Golgi apparatus. These data suggest that ORF3a plays little role in the targeting of S localization in the rER/Golgi apparatus. In addition, insertion of the 29-bp deletion fusing ORF8a/b into the single ORF8, noted in early-stage SARS-CoV human and civet cat isolates, had little if any impact on in vitro growth or RNA synthesis. All recombinant viruses replicated to wild-type levels in the murine model, suggesting that either the group-specific ORFs play little role in in vivo replication efficiency or that the mouse model is not of sufficient quality for discerning the role of the group-specific ORFs in disease origin and development.
0 Communities
1 Members
0 Resources
8 MeSH Terms
Moderate mutation rate in the SARS coronavirus genome and its implications.
Zhao Z, Li H, Wu X, Zhong Y, Zhang K, Zhang YP, Boerwinkle E, Fu YX
(2004) BMC Evol Biol 4: 21
MeSH Terms: Coronavirus, Evolution, Molecular, Genes, Viral, Genome, Viral, Mutagenesis, Phylogeny, SARS Virus, Viral Structural Proteins
Show Abstract · Added March 5, 2014
BACKGROUND - The outbreak of severe acute respiratory syndrome (SARS) caused a severe global epidemic in 2003 which led to hundreds of deaths and many thousands of hospitalizations. The virus causing SARS was identified as a novel coronavirus (SARS-CoV) and multiple genomic sequences have been revealed since mid-April, 2003. After a quiet summer and fall in 2003, the newly emerged SARS cases in Asia, particularly the latest cases in China, are reinforcing a wide-spread belief that the SARS epidemic would strike back. With the understanding that SARS-CoV might be with humans for years to come, knowledge of the evolutionary mechanism of the SARS-CoV, including its mutation rate and emergence time, is fundamental to battle this deadly pathogen. To date, the speed at which the deadly virus evolved in nature and the elapsed time before it was transmitted to humans remains poorly understood.
RESULTS - Sixteen complete genomic sequences with available clinical histories during the SARS outbreak were analyzed. After careful examination of multiple-sequence alignment, 114 single nucleotide variations were identified. To minimize the effects of sequencing errors and additional mutations during the cell culture, three strategies were applied to estimate the mutation rate by 1) using the closely related sequences as background controls; 2) adjusting the divergence time for cell culture; or 3) using the common variants only. The mutation rate in the SARS-CoV genome was estimated to be 0.80 - 2.38 x 10-3 nucleotide substitution per site per year which is in the same order of magnitude as other RNA viruses. The non-synonymous and synonymous substitution rates were estimated to be 1.16 - 3.30 x 10-3 and 1.67 - 4.67 x 10-3 per site per year, respectively. The most recent common ancestor of the 16 sequences was inferred to be present as early as the spring of 2002.
CONCLUSIONS - The estimated mutation rates in the SARS-CoV using multiple strategies were not unusual among coronaviruses and moderate compared to those in other RNA viruses. All estimates of mutation rates led to the inference that the SARS-CoV could have been with humans in the spring of 2002 without causing a severe epidemic.
0 Communities
1 Members
0 Resources
8 MeSH Terms
MHV-A59 gene 1 proteins are associated with two distinct membrane populations.
Denison MR, Sims AC
(2001) Adv Exp Med Biol 494: 655-61
MeSH Terms: Animals, Cell Fractionation, Cell Line, Cell Membrane, Membrane Proteins, Mice, Murine hepatitis virus, Precipitin Tests, RNA, Viral, Viral Proteins, Viral Structural Proteins
Added February 19, 2015
0 Communities
1 Members
0 Resources
11 MeSH Terms
The cell biology of coronavirus infection.
Prentice E, Denison MR
(2001) Adv Exp Med Biol 494: 609-14
MeSH Terms: Animals, Cell Line, Fluorescent Antibody Technique, Mice, Microscopy, Confocal, Murine hepatitis virus, Viral Proteins, Viral Structural Proteins
Show Abstract · Added February 19, 2015
The ability to obtain entire volume data on infected cells will allow us to define much more accurately the interactions of viral proteins with host cell structures such as ER, Golgi, and cytoskeletal elements. In addition, the demonstrated ability to express viral proteins fused to fluorescent markers in in live cells will allow us to follow specific proteins or complexes during the course of infection and to determine if exogenously expressed proteins are able to target to sites of active viral replication. This in turn will allow new approaches to the study of viral and cellular protein-protein interactions, as methods to study the biology and pathogenesis of MHV infection at a cellular level. Finally, the approaches described here will allow us to define protein complementation of defective viruses at a cellular level, rather than being dependent on population measurements of RNA, protein, or progeny virus. By combining these approaches with available biochemical and molecular biological approaches and the emerging reverse genetic and recombinant genetic approaches, rapid progress in understanding the details of coronavirus-cell interactions should be possible.
0 Communities
1 Members
0 Resources
8 MeSH Terms
Traffic control of completely assembled MHC class I molecules beyond the endoplasmic reticulum.
Joyce S
(1997) J Mol Biol 266: 993-1001
MeSH Terms: Amino Acid Sequence, Antigen Presentation, Biological Transport, Cell Compartmentation, Cell Membrane, Endoplasmic Reticulum, Exocytosis, Flow Cytometry, Glycoproteins, Golgi Apparatus, H-2 Antigens, Histocompatibility Antigen H-2D, Histocompatibility Antigens Class I, Protein Binding, Recombinant Proteins, Sequence Analysis, Sindbis Virus, Viral Structural Proteins, beta 2-Microglobulin
Show Abstract · Added October 2, 2015
It is generally assumed that MHC class I molecules arrive at the plasma membrane following biosynthesis, assembly and architectural editing in the endoplasmic reticulum by constitutive forward movement without requirement for specific signals (bulk flow). If this is true then all overexpressed completely assembled class I molecules should arrive at the cell surface. To study the itinerary of class I traffic beyond the endoplasmic reticulum, mammalian cells that overexpress 20 to 50-fold higher amounts of the constituent heavy and light chains were established. Thorough biochemical analyses revealed that such overexpressed molecules assemble with authentic peptides that contain the canonical class I binding anchor motif in almost 1:1 stoichiometry and impart thermal stability to the heterotrimeric complex. Despite complete assembly, however, only a fraction of the overexpressed molecules reaches the cell surface. Almost all of the overexpressed class I molecules are sialylated, thus traffic as far as the trans-Golgi or the trans-Golgi network. Overexpression of class I molecules do not seem to cause a "traffic jam" in the exocytic pathway because the kinetics of traffic of Sindbis virus structural proteins to the plasma membrane are almost identical when comparing the non-engineered and engineered cells. Thus the steady state expression of class I molecules at the cell surface is further controlled either in the Golgi apparatus or at the plasma membrane.
0 Communities
1 Members
0 Resources
19 MeSH Terms
Sequence diversity within the reovirus S2 gene: reovirus genes reassort in nature, and their termini are predicted to form a panhandle motif.
Chapell JD, Goral MI, Rodgers SE, dePamphilis CW, Dermody TS
(1994) J Virol 68: 750-6
MeSH Terms: Amino Acid Sequence, Animals, Base Sequence, Biological Evolution, Genes, Viral, Genetic Variation, L Cells, Mice, Molecular Sequence Data, Nucleic Acid Conformation, Phylogeny, RNA, Double-Stranded, Recombination, Genetic, Reoviridae, Sequence Analysis, RNA, Sequence Homology, Amino Acid, Species Specificity, Viral Core Proteins, Viral Structural Proteins
Show Abstract · Added December 10, 2013
To better understand genetic diversity within mammalian reoviruses, we determined S2 nucleotide and deduced sigma 2 amino acid sequences of nine reovirus strains and compared these sequences with those of prototype strains of the three reovirus serotypes. The S2 gene and sigma 2 protein are highly conserved among the four type 1, one type 2, and seven type 3 strains studied. Phylogenetic analyses based on S2 nucleotide sequences of the 12 reovirus strains indicate that diversity within the S2 gene is independent of viral serotype. Additionally, we found marked topological differences between phylogenetic trees generated from S1 and S2 gene nucleotide sequences of the seven type 3 strains. These results demonstrate that reovirus S1 and S2 genes have distinct evolutionary histories, thus providing phylogenetic evidence for lateral transfer of reovirus genes in nature. When variability among the 12 sigma 2-encoding S2 nucleotide sequences was analyzed at synonymous positions, we found that approximately 60 nucleotides at the 5' terminus and 30 nucleotides at the 3' terminus were markedly conserved in comparison with other sigma 2-encoding regions of S2. Predictions of RNA secondary structures indicate that the more conserved S2 sequences participate in the formation of an extended region of duplex RNA interrupted by a pair of stem-loops. Among the 12 deduced sigma 2 amino acid sequences examined, substitutions were observed at only 11% of amino acid positions. This finding suggests that constraints on the structure or function of sigma 2, perhaps in part because of its location in the virion core, have limited sequence diversity within this protein.
0 Communities
1 Members
0 Resources
19 MeSH Terms
Functional relationships and structural determinants of two bacteriophage T4 lysozymes: a soluble (gene e) and a baseplate-associated (gene 5) protein.
Mosig G, Lin GW, Franklin J, Fan WH
(1989) New Biol 1: 171-9
MeSH Terms: Amino Acid Sequence, Base Sequence, Genes, Viral, Models, Molecular, Molecular Sequence Data, Molecular Structure, Muramidase, Open Reading Frames, Protein Conformation, Protein Processing, Post-Translational, Sequence Homology, Nucleic Acid, Structure-Activity Relationship, T-Phages, Viral Proteins, Viral Structural Proteins
Show Abstract · Added March 20, 2014
Lysozymes have proved useful for analyzing the relation between protein structure and function and evolution. In bacteriophage T4, the major soluble lysozyme is the product of the e gene, gpe (gene product = gp). This lysozyme destroys the wall of its host, Escherichia coli, at the end of infection to release progeny particles. Phage T4 contains two additional lysozymes that facilitate penetration of the baseplates into host cell walls during adsorption. At least one of these, a 44-kD protein, is encoded by gene 5. We show here that a segment of the gp5 lysozyme amino acid sequence, deduced from the DNA sequence of gene 5, is remarkably similar to that of the T4 gene e lysozyme. Both T4 lysozymes are somewhat similar to the lysozyme of the Salmonella phage P22, but there is little significant DNA sequence homology among the two T4 lysozyme genes and the P22 lysozyme gene. We speculate that these lysozymes are adapted to differences in the composition of the cell walls of E. coli and S. typhimurium. The cloned gene 5 of the phage T4 directs synthesis of a 63-kD precursor protein that is approximately 19 kD larger than the gene 5 protein isolated from baseplates. Gp5 first associates with gp26 to form the central hub of this structure.(ABSTRACT TRUNCATED AT 250 WORDS)
0 Communities
1 Members
0 Resources
15 MeSH Terms