Cyclophilin, TRIM5, and innate immunity to HIV-1.
The peptidyl-prolyl isomerase cyclophilin A (CypA) binds a proline-rich loop on the surface of HIV-1 capsid (CA). This interaction increases HIV-1 infectivity in humans but promotes an anti-HIV-1 restriction activity in non-human primates. Efforts to understand these paradoxical effects of cyclophilin, along with more targeted approaches to uncover the genetic basis for HIV-1 restriction, led to the discovery of TRIM5 (tripartite motif protein 5), a CA-specific receptor for the retroviral core. The ensuing TRIM5 publication flurry established a paradigm of innate immunity in which the protein lattice of an invading retroviral core, rather than double-stranded RNA or lipopolysaccharide, is recognized by a multimeric, cytoplasmic receptor. CypA modulates HIV-1 virion core detection by this class of innate pattern recognition molecule, apparently by inducing subtle shifts in CA conformation.
Sokolskaja
Elena
E
Department of Microbiology, Columbia University, New York, NY 10032, USA.
Luban
Jeremy
J
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology*; D000818:Animals; D000090103:Antiviral Restriction Factors; D002213:Capsid / Q000502:physiology; D002352:Carrier Proteins / Q000737:chemistry / Q000502:physiology*; D021984:Cyclophilin A / Q000502:physiology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D013045:Species Specificity; D000070584:Tripartite Motif Proteins; D018523:Tropism; D025801:Ubiquitin / Q000502:physiology; D044767:Ubiquitin-Protein Ligases; D014779:Virus Replication
D000090103:Antiviral Restriction Factors; D002352:Carrier Proteins; D000070584:Tripartite Motif Proteins; D025801:Ubiquitin; C477346:TRIM5 protein, human; D044767:Ubiquitin-Protein Ligases; D021984:Cyclophilin A