scholarly journals Structure of the Dimerization Domain of the Rabies Virus Phosphoprotein

2010 ◽  
Vol 84 (7) ◽  
pp. 3707-3710 ◽  
Author(s):  
Ivan Ivanov ◽  
Thibaut Crépin ◽  
Marc Jamin ◽  
Rob W. H. Ruigrok
Keyword(s):  
Crystal Structure ◽  
Rabies Virus ◽  
Vesicular Stomatitis Virus ◽  
Hydrophobic Interactions ◽  
Sendai Virus ◽  
Hydrophobic Surfaces ◽  
Dimerization Domain ◽  
Tetramerization Domain ◽  
Helical Hairpin ◽  
Vesicular Stomatitis

ABSTRACT The crystal structure of the dimerization domain of rabies virus phosphoprotein was determined. The monomer consists of two α-helices that make a helical hairpin held together mainly by hydrophobic interactions. The monomer has a hydrophilic and a hydrophobic face, and in the dimer two monomers pack together through their hydrophobic surfaces. This structure is very different from the dimerization domain of the vesicular stomatitis virus phosphoprotein and also from the tetramerization domain of the Sendai virus phosphoprotein, suggesting that oligomerization is conserved but not structure.

scholarly journals Double-Layered Membrane Vesicles Released from Mammalian Cells Infected with Sendai Virus Expressing the Matrix Protein of Vesicular Stomatitis Virus

Virology ◽  
1999 ◽  
Vol 263 (1) ◽  
pp. 230-243 ◽  
Author(s):  
Takemasa Sakaguchi ◽  
Tsuneo Uchiyama ◽  
Yutaka Fujii ◽  
Katsuhiro Kiyotani ◽  
Atsushi Kato ◽  
...  
Keyword(s):  
Vesicular Stomatitis Virus ◽  
Mammalian Cells ◽  
Matrix Protein ◽  
Sendai Virus ◽  
Membrane Vesicles ◽  
The Matrix ◽  
Vesicular Stomatitis

scholarly journals Long-Term Persistent Vesicular Stomatitis Virus and Rabies Virus Infection of Cells In Vitro

1976 ◽  
Vol 33 (2) ◽  
pp. 193-211 ◽  
Author(s):  
J. J. Holland ◽  
L. P. Villarreal ◽  
R. M. Welsh ◽  
M. B. A. Oldstone ◽  
D. Kohne ◽  
...  
Keyword(s):  
Virus Infection ◽  
Rabies Virus ◽  
Vesicular Stomatitis Virus ◽  
Rabies Virus Infection ◽  
Vesicular Stomatitis

scholarly journals A Polyamide Inhibits Replication of Vesicular Stomatitis Virus by Targeting RNA in the Nucleocapsid

2018 ◽  
Vol 92 (8) ◽  
pp. e00146-18 ◽  
Author(s):  
Ryan H. Gumpper ◽  
Weike Li ◽  
Carlos H. Castañeda ◽  
M. José Scuderi ◽  
James K. Bashkin ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Vesicular Stomatitis Virus ◽  
Ebola Virus ◽  
Rna Viruses ◽  
Rna Virus ◽  
Viral Rna ◽  
Negative Strand ◽  
Double Stranded Dna ◽  
Vesicular Stomatitis ◽  
Syncytial Virus

ABSTRACTPolyamides have been shown to bind double-stranded DNA by complementing the curvature of the minor groove and forming various hydrogen bonds with DNA. Several polyamide molecules have been found to have potent antiviral activities against papillomavirus, a double-stranded DNA virus. By analogy, we reason that polyamides may also interact with the structured RNA bound in the nucleocapsid of a negative-strand RNA virus. Vesicular stomatitis virus (VSV) was selected as a prototype virus to test this possibility since its genomic RNA encapsidated in the nucleocapsid forms a structure resembling one strand of an A-form RNA duplex. One polyamide molecule, UMSL1011, was found to inhibit infection of VSV. To confirm that the polyamide targeted the nucleocapsid, a nucleocapsid-like particle (NLP) was incubated with UMSL1011. The encapsidated RNA in the polyamide-treated NLP was protected from thermo-release and digestion by RNase A. UMSL1011 also inhibits viral RNA synthesis in the intracellular activity assay for the viral RNA-dependent RNA polymerase. The crystal structure revealed that UMSL1011 binds the structured RNA in the nucleocapsid. The conclusion of our studies is that the RNA in the nucleocapsid is a viable antiviral target of polyamides. Since the RNA structure in the nucleocapsid is similar in all negative-strand RNA viruses, polyamides may be optimized to target the specific RNA genome of a negative-strand RNA virus, such as respiratory syncytial virus and Ebola virus.IMPORTANCENegative-strand RNA viruses (NSVs) include several life-threatening pathogens, such as rabies virus, respiratory syncytial virus, and Ebola virus. There are no effective antiviral drugs against these viruses. Polyamides offer an exceptional opportunity because they may be optimized to target each NSV. Our studies on vesicular stomatitis virus, an NSV, demonstrated that a polyamide molecule could specifically target the viral RNA in the nucleocapsid and inhibit viral growth. The target specificity of the polyamide molecule was proved by its inhibition of thermo-release and RNA nuclease digestion of the RNA bound in a model nucleocapsid, and a crystal structure of the polyamide inside the nucleocapsid. This encouraging observation provided the proof-of-concept rationale for designing polyamides as antiviral drugs against NSVs.

scholarly journals Phase Transitions Drive the Formation of Vesicular Stomatitis Virus Replication Compartments

mBio ◽  
2018 ◽  
Vol 9 (5) ◽  
Author(s):  
Bianca S. Heinrich ◽  
Zoltan Maliga ◽  
David A. Stein ◽  
Anthony A. Hyman ◽  
Sean P. J. Whelan
Keyword(s):  
Pattern Recognition ◽  
Phase Separation ◽  
Rabies Virus ◽  
Vesicular Stomatitis Virus ◽  
Rna Synthesis ◽  
Rna Viruses ◽  
Pattern Recognition Receptors ◽  
Replication Machinery ◽  
P Granules ◽  
Vesicular Stomatitis

ABSTRACTRNA viruses that replicate in the cell cytoplasm typically concentrate their replication machinery within specialized compartments. This concentration favors enzymatic reactions and shields viral RNA from detection by cytosolic pattern recognition receptors. Nonsegmented negative-strand (NNS) RNA viruses, which include some of the most significant human, animal, and plant pathogens extant, form inclusions that are sites of RNA synthesis and are not circumscribed by a membrane. These inclusions share similarities with cellular protein/RNA structures such as P granules and nucleoli, which are phase-separated liquid compartments. Here we show that replication compartments of vesicular stomatitis virus (VSV) have the properties of liquid-like compartments that form by phase separation. Expression of the individual viral components of the replication machinery in cells demonstrates that the 3 viral proteins required for replication are sufficient to drive cytoplasmic phase separation. Therefore, liquid-liquid phase separation, previously linked to organization of P granules, nucleolus homeostasis, and cell signaling, plays a key role in host-pathogen interactions. This work suggests novel therapeutic approaches to the problem of combating NNS RNA viral infections.IMPORTANCERNA viruses compartmentalize their replication machinery to evade detection by host pattern recognition receptors and concentrate the machinery of RNA synthesis. For positive-strand RNA viruses, RNA replication occurs in a virus-induced membrane-associated replication organelle. For NNS RNA viruses, the replication compartment is a cytoplasmic inclusion that is not circumscribed by a cellular membrane. Such structures were first observed in the cell bodies of neurons from humans infected with rabies virus and were termed Negri bodies. How the replication machinery that forms this inclusion remains associated in the absence of a membrane has been an enduring mystery. In this article, we present evidence that the VSV replication compartments form through phase separation. Phase separation is increasingly recognized as responsible for cellular structures as diverse as processing bodies (P-bodies) and nucleoli and was recently demonstrated for rabies virus. This article further links the fields of host-pathogen interaction with that of phase separation.

scholarly journals Crystal Structure of the Oligomerization Domain of the Phosphoprotein of Vesicular Stomatitis Virus

2006 ◽  
Vol 80 (6) ◽  
pp. 2808-2814 ◽  
Author(s):  
Haitao Ding ◽  
Todd J. Green ◽  
Shanyun Lu ◽  
Ming Luo
Keyword(s):  
Crystal Structure ◽  
Rna Polymerase ◽  
Vesicular Stomatitis Virus ◽  
Additional Stabilization ◽  
Vesicular Stomatitis ◽  
L Proteins ◽  
Α Helix ◽  
Nucleoprotein N ◽  
Β Sheet ◽  
Viral Nucleocapsid

ABSTRACT In the replication cycle of nonsegmented negative-strand RNA viruses, the viral RNA-dependent RNA polymerase (L) recognizes a nucleoprotein (N)-enwrapped RNA template during the RNA polymerase reaction. The viral phosphoprotein (P) is a polymerase cofactor essential for this recognition. We report here the 2.3-Å-resolution crystal structure of the central domain (residues 107 to 177) of P from vesicular stomatitis virus. The fold of this domain consists of a β hairpin, an α helix, and another β hairpin. The α helix provides the stabilizing force for forming a homodimer, while the two β hairpins add additional stabilization by forming a four-stranded β sheet through domain swapping between two molecules. This central dimer positions the N- and C-terminal domains of P to interact with the N and L proteins, allowing the L protein to specifically recognize the nucleocapsid-RNA template and to progress along the template while concomitantly assembling N with nascent RNA. The interdimer interactions observed in the noncrystallographic packing may offer insight into the mechanism of the RNA polymerase processive reaction along the viral nucleocapsid-RNA template.

scholarly journals Survey of virally mediated permeability changes

1980 ◽  
Vol 190 (3) ◽  
pp. 639-646 ◽  
Author(s):  
K A Foster ◽  
K Gill ◽  
K J Micklem ◽  
C A Pasternak
Keyword(s):  
Vesicular Stomatitis Virus ◽  
Viral Entry ◽  
Sendai Virus ◽  
Ependymal Cells ◽  
Cell Type ◽  
Organ Cultures ◽  
Nasal Turbinate ◽  
Permeability Changes ◽  
Mdbk Cells ◽  
Vesicular Stomatitis

1. Sendai virus causes permeability changes when added to freshly isolated brain cells (cerebellum or ependymal cells) or to a culture of forebrain cells. 2. Sendai virus causes permeability changes when added to organ cultures of ferret lung or nasal turbinate. Influenza virus causes no permeability changes under these conditions. 3. Rabies virus and vesicular-stomatitis virus, in contrast with Sendai virus, do not cause permeability changes in BHK cells or Lettrée cells. 4. Serum from patients suffering from viral hepatitis does not cause permeability changes in human leucocytes; addition to Sendai virus causes permeability changes. 5. It is concluded that permeability changes accompanying viral entry occur only with certain types of paramyxovirus, but that there is little restriction on cell type. 6. MDBK cells infected with Sendai virus show permeability changes during viral release, similar to those that occur during viral entry. Because these changes do not appear to be restricted to paramyxoviruses, they may have considerable clinical significance.

scholarly journals Role of Intermolecular Interactions of Vesicular Stomatitis Virus Nucleoprotein in RNA Encapsidation

2007 ◽  
Vol 82 (2) ◽  
pp. 674-682 ◽  
Author(s):  
Xin Zhang ◽  
Todd J. Green ◽  
Jun Tsao ◽  
Shihong Qiu ◽  
Ming Luo
Keyword(s):  
Crystal Structure ◽  
Intermolecular Interactions ◽  
Vesicular Stomatitis Virus ◽  
N Protein ◽  
P Protein ◽  
Intermolecular Contacts ◽  
Vesicular Stomatitis ◽  
Nucleoprotein N ◽  
Stable Ring

ABSTRACT The crystal structure of the vesicular stomatitis virus nucleoprotein (N) in complex with RNA reveals extensive and specific intermolecular interactions among the N molecules in the 10-member oligomer. What roles these interactions play in encapsidating RNA was studied by mutagenesis of the N protein. Three N mutants intended for disruption of the intermolecular interactions were designed and coexpressed with the phosphoprotein (P) in an Escherichia coli system previously described (T. J. Green et al., J. Virol. 74:9515-9524, 2000). Mutants N (Δ1-22), N (Δ347-352), and N (320-324, (Ala)5) lost RNA encapsidation and oligomerization but still bound with P. Another mutant, N (Ser290→Trp), was able to form a stable ring-like N oligomer and bind with the P protein but was no longer able to encapsidate RNA. The crystal structure of N (Ser290→Trp) at 2.8 Å resolution showed that this mutant can maintain all the same intermolecular interactions as the wild-type N except for a slight unwinding of the N-terminal lobe. These results suggest that the intermolecular contacts among the N molecules are required for encapsidation of the viral RNA.

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