Mechanism of altered Sindbis virus neurovirulence associated with a single-amino-acid change in the E2 Glycoprotein. 1991

P C Tucker, and D E Griffin
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.

The mechanism by which amino acid changes in the E1 and E2 surface glycoproteins of Sindbis virus affect neurovirulence is unknown. We have studied two recombinant viruses which differ in virulence. One (TE) contains Gly and the other (TES) contains Arg at position 172 in E2. TE causes more rapid death than TES in newborn mice. Both viruses replicate similarly in nonneuronal cells, but TE replicates more rapidly in the brains of newborn mice and in neuroblastoma cells. TE also induces earlier viral RNA synthesis in neuroblastoma cells. 35S-labeled TE binds more efficiently to brain and neuroblastoma cells, but not to nonneuronal cells, than TES. We propose that a region of the E2 glycoprotein affected by the amino acid occupying position 172 is important for binding to an alphavirus receptor on neurons and influences neurovirulence by this mechanism.

UI MeSH Term Description Entries
D008969 Molecular Sequence Data Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories. Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D009132 Muscles Contractile tissue that produces movement in animals. Muscle Tissue,Muscle,Muscle Tissues,Tissue, Muscle,Tissues, Muscle
D001921 Brain The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM. Encephalon
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D000595 Amino Acid Sequence The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION. Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000831 Animals, Newborn Refers to animals in the period of time just after birth. Animals, Neonatal,Animal, Neonatal,Animal, Newborn,Neonatal Animal,Neonatal Animals,Newborn Animal,Newborn Animals
D012845 Sindbis Virus The type species of ALPHAVIRUS normally transmitted to birds by CULEX mosquitoes in Egypt, South Africa, India, Malaya, the Philippines, and Australia. It may be associated with fever in humans. Serotypes (differing by less than 17% in nucleotide sequence) include Babanki, Kyzylagach, and Ockelbo viruses. Babanki virus,Kyzylagach virus,Ockelbo Virus
D014759 Viral Envelope Proteins Integral membrane proteins that are incorporated into the VIRAL ENVELOPE. They are glycosylated during VIRAL ASSEMBLY. Envelope Proteins, Viral,Viral Envelope Glycoproteins,Viral Envelope Protein,Virus Envelope Protein,Virus Peplomer Proteins,Bovine Leukemia Virus Glycoprotein gp51,Hepatitis Virus (MHV) Glycoprotein E2,LaCrosse Virus Envelope Glycoprotein G1,Simian Sarcoma Virus Glycoprotein 70,Viral Envelope Glycoprotein gPr90 (Murine Leukemia Virus),Viral Envelope Glycoprotein gp55 (Friend Virus),Viral Envelope Proteins E1,Viral Envelope Proteins E2,Viral Envelope Proteins gp52,Viral Envelope Proteins gp70,Virus Envelope Proteins,Envelope Glycoproteins, Viral,Envelope Protein, Viral,Envelope Protein, Virus,Envelope Proteins, Virus,Glycoproteins, Viral Envelope,Peplomer Proteins, Virus,Protein, Viral Envelope,Protein, Virus Envelope,Proteins, Viral Envelope,Proteins, Virus Envelope,Proteins, Virus Peplomer
D014774 Virulence The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. The pathogenic capacity of an organism is determined by its VIRULENCE FACTORS. Pathogenicity

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