Biomaterial Database

Vif counteracts a cyclophilin A-imposed inhibition of simian immunodeficiency viruses in human cells. 2007

Hiroaki Takeuchi, and Alicia Buckler-White, and Ritu Goila-Gaur, and Eri Miyagi, and Mohammad A Khan, and Sandrine Opi, and Sandra Kao, and Elena Sokolskaja, and Thomas Pertel, and Jeremy Luban, and Klaus Strebel

Laboratory of Molecular Microbiology, Viral Biochemistry Section, National Institute of Allergy and Infectious Diseases, NIH, Building 4, Room 310, 4 Center Drive, MSC 0460, Bethesda, Maryland 20892-0460, USA.

Vif is a primate lentiviral accessory protein that is crucial for viral infectivity. Vif counteracts the antiviral activity of host deaminases such as APOBEC3G and APOBEC3F. We now report a novel function of African green monkey simian immunodeficiency virus (SIVagm) Vif that promotes replication of SIVagm in human cells lacking detectable deaminase activity. We found that cyclophilin A (CypA) was excluded from wild-type SIV particles but was efficiently packaged into vif-deficient SIVagm virions. The presence of CypA in vif-defective SIVagm was correlated with reduced viral replication. Infection of CypA knockout Jurkat cells or treatment of Jurkat cells with cyclosporine A eliminated the Vif-sensitive inhibition and resulted in replication profiles that were similar for wild-type and vif-deficient SIVagm. Importantly, the inhibitory effect of CypA was restricted to virus-producing cells and was TRIM5alpha independent. The abilities of SIVagm Vif to inhibit encapsidation of CypA and to increase viral infectivity were shared by rhesus macaque SIV Vif and thus seem to be general properties of SIV Vif proteins. Exclusion of CypA from SIVagm particles was not associated with intracellular degradation, suggesting a mode of Vif action distinct from that proposed for APOBEC3G. This is the first report of a novel vif-sensitive antiviral activity of human CypA that may limit zoonotic transmission of SIV and the first demonstration of CypA encapsidation into a virus other than human immunodeficiency virus type 1.

UI	MeSH Term	Description	Entries
D007166	Immunosuppressive Agents	Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of T-CELLS or by inhibiting the activation of HELPER CELLS. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of INTERLEUKINS and other CYTOKINES are emerging.	Immunosuppressant,Immunosuppressive Agent,Immunosuppressants,Agent, Immunosuppressive,Agents, Immunosuppressive
D002352	Carrier Proteins	Proteins that bind or transport specific substances in the blood, within the cell, or across cell membranes.	Binding Proteins,Carrier Protein,Transport Protein,Transport Proteins,Binding Protein,Protein, Carrier,Proteins, Carrier
D002460	Cell Line	Established cell cultures that have the potential to propagate indefinitely.	Cell Lines,Line, Cell,Lines, Cell
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000070584	Tripartite Motif Proteins	A protein family defined by the presence of three ZINC FINGER domains, one of which is a RING FINGER DOMAIN, a coiled-coil region, and a highly variable C-terminal region. They function in many cellular processes including APOPTOSIS and CELL CYCLE regulation.	RBCC Protein,TRIM Protein,Tripartite Motif Protein,RBCC Protein Family,RBCC Proteins,TRIM Protein Family,TRIM Proteins,Family, RBCC Protein,Family, TRIM Protein,Motif Protein, Tripartite,Motif Proteins, Tripartite,Protein Family, RBCC,Protein Family, TRIM,Protein, RBCC,Protein, TRIM,Protein, Tripartite Motif,Proteins, RBCC,Proteins, TRIM,Proteins, Tripartite Motif
D000090103	Antiviral Restriction Factors	A broad category of endogenous host cellular factors upregulated in response to pathogens (i.e., INTERFERON-stimulated genes) and recruited to interfere with VIRAL REPLICATION and/or trigger host antiviral CELLULAR IMMUNE RESPONSE.	Antiviral Effectors,Cellular Restriction Factors,Host Cell Restriction Factors,Restriction Factors, Antiviral
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
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
D014779	Virus Replication	The process of intracellular viral multiplication, consisting of the synthesis of PROTEINS; NUCLEIC ACIDS; and sometimes LIPIDS, and their assembly into a new infectious particle.	Viral Replication,Replication, Viral,Replication, Virus,Replications, Viral,Replications, Virus,Viral Replications,Virus Replications
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