title: Cyclophilin B enhances HIV-1 infection.
abstract: Cyclophilin B (CypB) is a member of the immunophilin family and intracellular chaperone. It predominantly localizes to the ER, but also contains a nuclear localization signal and is secreted from cells. CypB has been shown to interact with the Gag protein of human immunodeficiency type 1 (HIV-1). Several proteomic and genetic studies identified it as a potential factor involved in HIV replication. Herein, we show that over-expression of CypB enhances HIV infection by increasing nuclear import of viral DNA. This enhancement was unaffected by cyclosporine treatment and requires the N-terminus of the protein. The N-terminus contains an ER leader sequence, putative nuclear localization signal, and is required for secretion. Deletion of the N-terminus resulted in mislocalization from the ER and suppression of HIV infection. Passive transfer experiments showed that secreted CypB did not impact HIV infection. Combined, these experiments show that intracellular CypB modulates a pathway of HIV nuclear import.
authors.affiliation: Department of Medical Microbiology and Immunology, Creighton University, Omaha, NE, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: DeBoer
authors.affiliation: Department of Medical Microbiology and Immunology, Creighton University, Omaha, NE, USA.
authors.forename: Christian J
authors.initials: CJ
authors.lastname: Madson
authors.affiliation: Department of Medical Microbiology and Immunology, Creighton University, Omaha, NE, USA; The Nebraska Center for Virology, University of Nebraska, Lincoln, NE, USA. Electronic address: michaelbelshan@creighton.edu.
authors.forename: Michael
authors.initials: M
authors.lastname: Belshan
mesh_terms: D020816:Amino Acid Motifs; D002467:Cell Nucleus / Q000821:virology; D021983:Cyclophilins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015658:HIV Infections / Q000201:enzymology* / Q000235:genetics / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000201:enzymology / Q000821:virology
chemical_list: D012367:RNA, Viral; C081786:cyclophilin B; D021983:Cyclophilins
keywords: Cyclophilin b; CypB; HIV-1; Nuclear import; Virus-host interactions