scholarly journals Structural and Evolutionary Insights Into the Binding of Host Receptors by the Rabies Virus Glycoprotein

2021 ◽  
Vol 11 ◽  
Author(s):  
Manar E. Khalifa ◽  
Leonie Unterholzner ◽  
Muhammad Munir
Keyword(s):  
G Protein ◽  
Rabies Virus ◽  
Viral Evolution ◽  
Bioinformatic Analysis ◽  
Susceptible Host ◽  
Acetyl Choline ◽  
Host Interactions ◽  
Protein Protein Interaction ◽  
Glycoprotein G ◽  
Typical Model

Rabies represents a typical model for spillover of zoonotic viral diseases among multiple hosts. Understanding the success of rabies virus (RV) in switching hosts requires the analysis of viral evolution and host interactions. In this study, we have investigated the structural and sequence analysis of host receptors among different RV susceptible host species. Our extensive bioinformatic analysis revealed the absence of the integrin plexin domain in the integrin β1 (ITGB1) receptor of the black fruit bats in the current annotation of the genome. Interestingly, the nicotinic acetyl choline receptor (nAChR) interaction site with the glycoprotein (G) of RV was conserved among different species. To study the interaction dynamics between RV-G protein and the RV receptors, we constructed and analyzed structures of RV receptors and G proteins using homology modeling. The molecular docking of protein-protein interaction between RV-G protein and different host receptors highlighted the variability of interacting residues between RV receptors of different species. These in silico structural analysis and interaction mapping of viral protein and host receptors establish the foundation to understand complex entry mechanisms of RV entry, which may facilitate the understanding of receptor mediated spillover events in RV infections and guide the development of novel vaccines to contain the infection.

scholarly journals Pathogenicity of Different Rabies Virus Variants Inversely Correlates with Apoptosis and Rabies Virus Glycoprotein Expression in Infected Primary Neuron Cultures

1999 ◽  
Vol 73 (1) ◽  
pp. 510-518 ◽  
Author(s):  
Kinjiro Morimoto ◽  
D. Craig Hooper ◽  
Sergei Spitsin ◽  
Hilary Koprowski ◽  
Bernhard Dietzschold
Keyword(s):  
Protein Expression ◽  
G Protein ◽  
Rabies Virus ◽  
Antigenic Site ◽  
Expression Levels ◽  
N Protein ◽  
Adult Mice ◽  
Glycoprotein G ◽  
Neuronal Processes ◽  
Nucleoprotein N

ABSTRACT The mouse-adapted rabies virus strain CVS-24 has stable variants, CVS-B2c and CVS-N2c, which differ greatly in their pathogenicity for normal adult mice and in their ability to infect nonneuronal cells. The glycoprotein (G protein), which has previously been implicated in rabies virus pathogenicity, shows substantial structural differences between these variants. Although prior studies have identified antigenic site III of the G protein as the major pathogenicity determinant, CVS-B2c and CVS-N2c do not vary at this site. The possibility that pathogenicity is inversely related to G protein expression levels is suggested by the finding that CVS-B2c, the less pathogenic variant, expresses at least fourfold-higher levels of G protein than CVS-N2c in infected neurons. Although there is some difference between CVS-B2c- and CVS-N2c-infected neurons in G protein mRNA expression levels, the differential expression of G protein appears to be largely determined by posttranslational mechanisms that affect G protein stability. Pulse-chase experiments indicated that the G protein of CVS-B2c is degraded more slowly than that of CVS-N2c. The accumulation of G protein correlated with the induction of programmed cell death in CVS-B2c-infected neurons. The extent of apoptosis was considerably lower in CVS-N2c-infected neurons, where G protein expression was minimal. While nucleoprotein (N protein) expression levels were similar in neurons infected with either variant, the transport of N protein into neuronal processes was strongly inhibited in CVS-B2c-infected cells. Thus, downregulation of G protein expression in neuronal cells evidently contributes to rabies virus pathogenesis by preventing apoptosis and the apparently associated failure of the axonal transport of N protein.

scholarly journals Bioinformatic Analysis of Structure and Function of LIM Domains of Human Zyxin Family Proteins

2021 ◽  
Vol 22 (5) ◽  
pp. 2647
Author(s):  
M. Quadir Siddiqui ◽  
Maulik D. Badmalia ◽  
Trushar R. Patel
Keyword(s):  
Nucleic Acid ◽  
Nuclear Export ◽  
Consensus Sequence ◽  
Nuclear Export Signal ◽  
Bioinformatic Analysis ◽  
Nucleic Acid Binding ◽  
Protein Protein Interaction ◽  
Lim Domains ◽  
Protein Nucleic Acid ◽  
And Function

Members of the human Zyxin family are LIM domain-containing proteins that perform critical cellular functions and are indispensable for cellular integrity. Despite their importance, not much is known about their structure, functions, interactions and dynamics. To provide insights into these, we used a set of in-silico tools and databases and analyzed their amino acid sequence, phylogeny, post-translational modifications, structure-dynamics, molecular interactions, and functions. Our analysis revealed that zyxin members are ohnologs. Presence of a conserved nuclear export signal composed of LxxLxL/LxxxLxL consensus sequence, as well as a possible nuclear localization signal, suggesting that Zyxin family members may have nuclear and cytoplasmic roles. The molecular modeling and structural analysis indicated that Zyxin family LIM domains share similarities with transcriptional regulators and have positively charged electrostatic patches, which may indicate that they have previously unanticipated nucleic acid binding properties. Intrinsic dynamics analysis of Lim domains suggest that only Lim1 has similar internal dynamics properties, unlike Lim2/3. Furthermore, we analyzed protein expression and mutational frequency in various malignancies, as well as mapped protein-protein interaction networks they are involved in. Overall, our comprehensive bioinformatic analysis suggests that these proteins may play important roles in mediating protein-protein and protein-nucleic acid interactions.

scholarly journals Development of a rabies virus-based retrograde tracer with high trans-monosynaptic efficiency by reshuffling glycoprotein

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Fan Jia ◽  
Li Li ◽  
Haizhou Liu ◽  
Pei Lv ◽  
Xiangwei Shi ◽  
...  
Keyword(s):  
Experimental Data ◽  
Rabies Virus ◽  
Oncolytic Virus ◽  
Neural Circuits ◽  
Bioinformatic Analysis ◽  
Cell Engineering ◽  
Bias Score ◽  
Codon Pair Bias ◽  
Codon Pair

AbstractRabies virus (RV) is the most widely used vector for mapping neural circuits. Previous studies have shown that the RV glycoprotein can be a target to improve the retrograde transsynaptic tracing efficiency. However, the current versions still label only a small portion of all presynaptic neurons. Here, we reshuffled the oG sequence, a chimeric glycoprotein, with positive codon pair bias score (CPBS) based on bioinformatic analysis of mouse codon pair bias, generating ooG, a further optimized glycoprotein. Our experimental data reveal that the ooG has a higher expression level than the oG in vivo, which significantly increases the tracing efficiency by up to 12.6 and 62.1-fold compared to oG and B19G, respectively. The new tool can be used for labeling neural circuits Therefore, the approach reported here provides a convenient, efficient and universal strategy to improve protein expression for various application scenarios such as trans-synaptic tracing efficiency, cell engineering, and vaccine and oncolytic virus designs.

scholarly journals Phylogenetic analysis of glycoprotein (G) gene of rabies virus isolated from spotted deer, Delhi, 2016

2018 ◽  
Vol 73 ◽  
pp. 385
Author(s):  
G. Singh ◽  
R. Jaiswal ◽  
M. Chhabra ◽  
N.K. Gupta ◽  
M. Singhai ◽  
...  
Keyword(s):  
Phylogenetic Analysis ◽  
Rabies Virus ◽  
Glycoprotein G ◽  
Spotted Deer

Expression of the ectodomain of the rabies virus glycoprotein G in insect cells for diagnostic purposes in vaccinated llamas

2018 ◽  
Vol 44 ◽  
pp. S158
Author(s):  
A.M. Targovnik ◽  
G. Mc Callum ◽  
M.B. Arregui ◽  
L.F. Bracco ◽  
M. Micucci ◽  
...  
Keyword(s):  
Rabies Virus ◽  
Insect Cells ◽  
Rabies Virus Glycoprotein ◽  
Virus Glycoprotein ◽  
Glycoprotein G

scholarly journals The cytoplasmic tail of the rabies virus G protein is an essential domain controlling death/survival in human neuronal cells

2008 ◽  
Vol 2 (S1) ◽  
Author(s):  
Christophe Prehaud ◽  
Mireille Lafage ◽  
Gene S Tan ◽  
Françoise Mégret ◽  
Pauline Ménager ◽  
...  
Keyword(s):  
G Protein ◽  
Rabies Virus ◽  
Neuronal Cells ◽  
Cytoplasmic Tail ◽  
Essential Domain ◽  
Human Neuronal Cells

scholarly journals Quantifying relative virulence: when μ max fails and AUC alone just is not enough

2020 ◽  
Author(s):  
Ruben Michael Ceballos ◽  
Carson Len Stacy
Keyword(s):  
Specific Growth ◽  
Area Under The Curve ◽  
Maximum Specific Growth Rate ◽  
Curve Analysis ◽  
Growth Curve Analysis ◽  
Virus Infections ◽  
Susceptible Host ◽  
Host Interactions ◽  
Biological Phenomena ◽  
Single Host

A challenge in virology is quantifying relative virulence (V R) between two (or more) viruses that exhibit different replication dynamics in a given susceptible host. Host growth curve analysis is often used to mathematically characterize virus–host interactions and to quantify the magnitude of detriment to host due to viral infection. Quantifying V R using canonical parameters, like maximum specific growth rate (μ max), can fail to provide reliable information regarding virulence. Although area-under-the-curve (AUC) calculations are more robust, they are sensitive to limit selection. Using empirical data from Sulfolobus Spindle-shaped Virus (SSV) infections, we introduce a novel, simple metric that has proven to be more robust than existing methods for assessing V R. This metric (I SC) accurately aligns biological phenomena with quantified metrics to determine V R. It also addresses a gap in virology by permitting comparisons between different non-lytic virus infections or non-lytic versus lytic virus infections on a given host in single-virus/single-host infections.

Intracellular transport of the glycoprotein of VSV is inhibited by CCCP at a late stage of post-translational processing

1989 ◽  
Vol 92 (4) ◽  
pp. 633-642
Author(s):  
J.K. Burkhardt ◽  
Y. Argon
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Surface ◽  
G Protein ◽  
Vesicular Stomatitis Virus ◽  
Late Stage ◽  
Intracellular Transport ◽  
Post Translational Modifications ◽  
Glycoprotein G ◽  
Golgi Compartment ◽  
Vesicular Stomatitis

The appearance of newly synthesized glycoprotein (G) of vesicular stomatitis virus at the surface of infected BHK cells is inhibited reversibly by treatment with carbonylcyanide m-chlorophenylhydrazone (CCCP). Under the conditions used, CCCP treatment depleted the cellular ATP levels by 40–60%, consistent with inhibition of transport at energy-requiring stages. The G protein that accumulates in cells treated with CCCP is heterogeneous. Most of it is larger than the newly synthesized G protein, is acylated with palmitic acid, and is resistant to endoglycosidase H (Endo H). Most of the arrested G protein is also sensitive to digestion with neuraminidase, indicating that it has undergone at least partial sialylation. A minority of G protein accumulates under these conditions in a less-mature form, suggesting its inability to reach the mid-Golgi compartment. The oligosaccharides of this G protein are Endo-H-sensitive and seem to be partly trimmed. Whereas sialylated G protein was arrested intracellularly, fucose-labelled G protein was able to complete its transport to the cell surface, indicating that a late CCCP-sensitive step separates sialylation from fucosylation. These post-translational modifications indicate that G protein can be transported as far as the trans-Golgi in the presence of CCCP and is not merely arrested in the endoplasmic reticulum.

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