Title

Cyclophilin A and HIV-1 Replication

UMMS Affiliation

Program in Molecular Medicine; Department of Biochemistry and Molecular Pharmacology

Publication Date

10-1-2014

Document Type

Book Chapter

Disciplines

Amino Acids, Peptides, and Proteins | Biochemistry | Genetic Phenomena | Molecular Biology | Molecular Genetics | Virology | Viruses

Abstract

The gag gene of HIV-1 and other retroviruses encodes a polyprotein that is sufficient to direct the assembly of virions (Life Cycle Overview; Virus Assembly; Franke et al. 1994). The Gag polyprotein is targeted to the plasma membrane where it buds out of the cell. Concurrent with virion budding, the viral protease is activated. This cleaves the Gag polyprotein into at least six mature, gag-encoded, virion-associated proteins, among which is the matrix protein (MA), which associates with the inner face of the virion membrane, and the highly basic, zinc-finger-containing nucleocapsid protein (NC), which coats the viral genomic RNA. The capsid protein (CA) undergoes a large conformational transformation upon proteolytic cleavage and collapses to form the protein lattice that encases the viral genome at the core of the virion (HIV-1 Virion Structure).

Following membrane fusion with a susceptible target cell, the CA core is released into the cytoplasm where it regulates reverse transcription (Braaten et al. 1996a). What happens to the CA core lattice at this stage of the virus replication cycle is frankly unclear. It may crumble into monomers of CA or small CA multimers, or it might disassemble in a more complex, directed fashion. Some believe that the CA lattice core persists in the cytoplasm and docks to the nuclear pore – perhaps via interaction with discrete nucleoporins like Nup358 (Nuclear Import: HIV-1 Goes NUPs), while others have provided evidence that CA multimers traffic to the nucleus with the preintegration complex (Integration).

Keywords

CyPA Protein, Immunosuppressive Drug Cyclosporine, Adjacent Amino Acid Residue, CypA Interaction, CypA Protein Level

DOI of Published Version

10.1007/978-1-4614-9610-6_74-1

Source

Luban J. (2013) Cyclophilin A and HIV-1 Replication. In: Hope T., Stevenson M., Richman D. (eds) Encyclopedia of AIDS. Springer, New York, NY

Journal/Book/Conference Title

Encyclopedia of AIDS

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