Journal ArticleDOI
Substitutions of 169Lys and 173Thr in nonstructural protein 1 influence the infectivity and pathogenicity of XJ-160 virus
TLDR
Viral forms BR-173 and BR-6973 showed increased sensitivity to 3-deazaadenosine (3-DZA), which inhibits S-adenosylhomocysteine hydrolase, and mutagenesis at residue 169 in the nsP1 region of XJ-160 is lethal, but mutation at residue 173 from Thr to Ile enhances viral infectivity and neurovirulence and suppresses the lethal effect of the mutation at residues 169.Abstract:
An infectious clone (pBR-XJ160) was constructed using the full-length cDNA of the Sindbis-like XJ-160 virus. Two nucleotide mutations, causing amino acid changes at residue 169 from Lys to Arg and at residue 173 from Thr to Ile in the nonstructural protein (nsP) 1 coding region, strongly influenced the infectivity of in vitro-synthesized RNA. We used site-directed mutagenesis to obtain clones encoding a change to Arg at residue 169 of nsP1 (pBR-169), a change to Ile at residue 173 (pBR-173), or both changes (pBR-6973). Infectivity of RNA from pBR-169 was abolished, but viral forms BR-173 and BR-6973 were obtained from pBR-173 and pBR-6973, respectively. Further, BR-173 exhibited higher propagation than BR-XJ160 in cell culture and higher neurovirulence in a suckling mouse model. BR-6973 possessed an intermediate phenotype. BR-173 and BR-6973 showed increased sensitivity to 3-deazaadenosine (3-DZA), which inhibits S-adenosylhomocysteine hydrolase. Thus, mutagenesis at residue 169 in the nsP1 region of XJ-160 is lethal, but mutation at residue 173 from Thr to Ile enhances viral infectivity and neurovirulence and suppresses the lethal effect of the mutation at residue 169. These mutations might be associated with the RNA methyltransferase (MTase) activity of nsP1.read more
Citations
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Journal ArticleDOI
Understanding the alphaviruses: recent research on important emerging pathogens and progress towards their control.
Ernest A. Gould,Bruno Coutard,Hélène Malet,Benjamin Morin,S. Jamal,Scott C. Weaver,Alexander E. Gorbalenya,Gregory Moureau,Cécile Baronti,I. Delogu,Naomi L. Forrester,Khasnatinov Ma,T.S. Gritsun,X. de Lamballerie,Bruno Canard +14 more
TL;DR: Progress in understanding the structure and function of alphavirus replicative enzymes achieved under the VIZIER programme and the development of new disease control strategies are reviewed.
Journal ArticleDOI
Newly recognized mosquito-associated viruses in mainland China, in the last two decades.
TL;DR: The purpose of this review is to describe the newly isolated mosquito-associated viruses in mainland China which belong to five viral families, including their virological properties, phylogenetic relationships, serological evidence, as well as to appeal the public health concentration worldwide.
Journal ArticleDOI
Interaction of E2 Glycoprotein with Heparan Sulfate Is Crucial for Cellular Infection of Sindbis Virus
Wuyang Zhu,Lihua Wang,Yi-liang Yang,Juan Jia,Shihong Fu,Yun Feng,Ying He,Jin-Ping Li,Guodong Liang +8 more
TL;DR: It is confirmed that interaction of E2 protein with HS is crucial for cellular infection of SINV based on the reverse genetic system of XJ-160 virus, a Sindbis-like virus (SINLV).
Book ChapterDOI
Additional material
TL;DR: These investigations indicate that HS-dependent infection is an adaptation through the mutation for positively charged amino acid (aa), which frequently arise in laboratory strains during laboratory strains of alpha-viruses.
Journal ArticleDOI
Homology Modeling and Docking to Potential Novel Inhibitor for Chikungunya (37997) Protein nsP2 Protease
TL;DR: It is shown that LIGAND_4 could be a promising inhibitor for nsP2 Protease of CHIKV virus as the drug target and computational methods have been used to find the best interaction site in the protease protein and identify the best ligand compounds for inhibiting the nsP 2 protein.
References
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Journal ArticleDOI
The alphaviruses: gene expression, replication, and evolution.
TL;DR: This article corrects the article on p. 496 in vol.
Journal ArticleDOI
Polypeptide requirements for assembly of functional Sindbis virus replication complexes: a model for the temporal regulation of minus- and plus-strand RNA synthesis
TL;DR: It is shown that nsP4 can function as the polymerase for both minus‐ and plus‐strand RNA synthesis, and proposed that processing of P123 switches the template preference of the complex to minus‐strands, resulting in efficient synthesis of plus-strand genomic and subgenomic RNAs and shut‐off of minus‐ Strad RNA synthesis.
Journal ArticleDOI
Internally located cleavable signal sequences direct the formation of Semliki Forest virus membrane proteins from a polyprotein precursor.
Peter Liljeström,Henrik Garoff +1 more
TL;DR: It is concluded that the 6K protein is a transmembrane polypeptide with its N terminus on the luminal side of the membrane (type I) and that all three membrane proteins is directed by alternating signal and stop-transfer sequences that function in translocation and cleavage of the virus precursor polyprotein.
Journal ArticleDOI
Sindbis virus proteins nsP1 and nsP2 contain homology to nonstructural proteins from several RNA plant viruses.
TL;DR: In this article, the authors show that the genetic organization of tobacco mosaic virus (TMV) differs considerably from that of the tripartite viruses (alfalfa mosaic virus [AlMV] and brome mosaic virus[BMV]), all of these RNA plant viruses share three domains of homology among their nonstructural proteins.
Sindbis VirusProteins nsPlandnsP2Contain Homology to Nonstructural Proteins fromSeveral RNA Plant Viruses
TL;DR: The results strengthen the view that the four viruses share mechanistic similarities in their replication strategies and may be evolutionarily related and suggest that either the AlMV 1a, BMV 1 a, and TMV p126 proteins are multifunctional or Sindbis proteins nsP1 and nsP2 function together as subunits in a single complex.
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