Biomaterial Database

Neurovirulent simian immunodeficiency virus incorporates a Nef-associated kinase activity into virions. 1998

M T Flaherty, and S A Barber, and J E Clements

Division of Comparative Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.

We have demonstrated that a molecular clone, SIV/17E-Fr, is neurovirulent in vivo and molecular analyses of this virus in primary macrophages and neuroendothelial cells mapped the domains critical for this phenotype to the transmembrane and Nef proteins. The Nef protein is crucial for virus replication and pathogenesis in SIV-infected rhesus macaques. In addition, both HIV and SIV require full-length Nef proteins for efficient virus replication in primary cells and optimal virion infectivity. To characterize further the contribution of Nef to enhanced infectivity and replication, we analyzed virus particles from a number of SIV recombinant clones. These clones contained nef genes derived from either a lymphocyte-tropic (SIVmac239) or neurovirulent (SIV/17E-Fr) virus or a nef gene with a premature stop codon or deletion. Immunoprecipitation of Nef from virus particles revealed that SIV Nef is incorporated into virions. Incorporation of the Nef protein was dependent on the presence of the N-terminal myristoylation sequence in the nef gene. In addition, enhanced replication and virion infectivity was associated only with viruses containing the full-length Nef protein. To investigate a potential mechanism of virion modification by Nef, in vitro kinase assays were performed on the virion-derived Nef protein. Nef-associated kinase activity was detected only in virions containing Nef sequences derived from the neurovirulent virus SIV/17E-Fr. Thus, these results suggest that selection for specific nef sequences occurs in vivo and has a significant effect on virus replication in specific cells and organs.

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
D009227	Myristic Acids	14-carbon saturated monocarboxylic acids.	Tetradecanoic Acids,Acids, Myristic,Acids, Tetradecanoic
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
D014407	Tumor Cells, Cultured	Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.	Cultured Tumor Cells,Neoplastic Cells, Cultured,Cultured Neoplastic Cells,Cell, Cultured Neoplastic,Cell, Cultured Tumor,Cells, Cultured Neoplastic,Cells, Cultured Tumor,Cultured Neoplastic Cell,Cultured Tumor Cell,Neoplastic Cell, Cultured,Tumor Cell, Cultured
D014771	Virion	The infective system of a virus, composed of the viral genome, a protein core, and a protein coat called a capsid, which may be naked or enclosed in a lipoprotein envelope called the peplos.	Virus Particle,Viral Particle,Viral Particles,Particle, Viral,Particle, Virus,Particles, Viral,Particles, Virus,Virions,Virus Particles
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
D015302	Simian Immunodeficiency Virus	Species of the genus LENTIVIRUS, subgenus primate immunodeficiency viruses (IMMUNODEFICIENCY VIRUSES, PRIMATE), that induces acquired immunodeficiency syndrome in monkeys and apes (SAIDS). The genetic organization of SIV is virtually identical to HIV.	SIV (Simian immunodeficiency virus),Immunodeficiency Viruses, Simian,Simian Immunodeficiency Viruses,Immunodeficiency Virus, Simian
D015693	Gene Products, nef	Products of the retroviral NEF GENE. They play a role as accessory proteins that influence the rate of viral infectivity and the destruction of the host immune system. nef gene products were originally found as factors that trans-suppress viral replication and function as negative regulators of transcription. nef stands for negative factor.	nef Gene Products,nef Protein,3'-orf Protein,Gene Product, nef,3' orf Protein,nef Gene Product
D017346	Protein Serine-Threonine Kinases	A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.	Protein-Serine-Threonine Kinases,Serine-Threonine Protein Kinase,Serine-Threonine Protein Kinases,Protein-Serine Kinase,Protein-Serine-Threonine Kinase,Protein-Threonine Kinase,Serine Kinase,Serine-Threonine Kinase,Serine-Threonine Kinases,Threonine Kinase,Kinase, Protein-Serine,Kinase, Protein-Serine-Threonine,Kinase, Protein-Threonine,Kinase, Serine-Threonine,Kinases, Protein Serine-Threonine,Kinases, Protein-Serine-Threonine,Kinases, Serine-Threonine,Protein Kinase, Serine-Threonine,Protein Kinases, Serine-Threonine,Protein Serine Kinase,Protein Serine Threonine Kinase,Protein Serine Threonine Kinases,Protein Threonine Kinase,Serine Threonine Kinase,Serine Threonine Kinases,Serine Threonine Protein Kinase,Serine Threonine Protein Kinases