title: Multiple restrictions of human immunodeficiency virus type 1 in feline cells.
abstract: The productive replication of human immunodeficiency virus type 1 (HIV-1) occurs exclusively in defined cells of human or chimpanzee origin, explaining why heterologous animal models for HIV replication, pathogenesis, vaccination, and therapy are not available. This lack of an animal model for HIV-1 studies prompted us to examine the susceptibility of feline cells in order to evaluate the cat (Felis catus) as an animal model for studying HIV-1. Here, we report that feline cell lines harbor multiple restrictions with respect to HIV-1 replication. The feline CD4 receptor does not permit virus infection. Feline T-cell lines MYA-1 and FeT-1C showed postentry restrictions resulting in low HIV-1 luciferase reporter activity and low expression of viral Gag-Pol proteins when pseudotyped vectors were used. Feline fibroblastic CrFK and KE-R cells, expressing human CD4 and CCR5, were very permissive for viral entry and HIV-long terminal repeat-driven expression but failed to support spreading infection. KE-R cells displayed a profound block with respect to release of HIV-1 particles. In contrast, CrFK cells allowed very efficient particle production; however, the CrFK cell-derived HIV-1 particles had low specific infectivity. We subsequently identified feline apolipoprotein B-editing catalytic polypeptide 3 (feAPOBEC3) proteins as active inhibitors of HIV-1 particle infectivity. CrFK cells express at least three different APOBEC3s: APOBEC3C, APOBEC3H, and APOBEC3CH. While the feAPOBEC3C did not significantly inhibit HIV-1, the feAPOBEC3H and feAPOBEC3CH induced G to A hypermutations of the viral cDNA and reduced the infectivity approximately 10- to approximately 40-fold.
authors: Division of Medical Biotechnology, Paul-Ehrlich-Institut, Paul-Ehrlich-Str. 51-59, 63225 Langen, Germany. mueca@pei.de
authors: Carsten
authors: C
authors: Münk
authors: Jörg
authors: J
authors: Zielonka
authors: Hannelore
authors: H
authors: Constabel
authors: Björn-Philipp
authors: BP
authors: Kloke
authors: Benjamin
authors: B
authors: Rengstl
authors: Marion
authors: M
authors: Battenberg
authors: Francesca
authors: F
authors: Bonci
authors: Mauro
authors: M
authors: Pistello
authors: Martin
authors: M
authors: Löchelt
authors: Klaus
authors: K
authors: Cichutek
mesh_terms: D000818:Animals; D001483:Base Sequence; D015704:CD4 Antigens / Q000378:metabolism; D002415:Cats; D002460:Cell Line; D043525:Cytosine Deaminase / Q000378:metabolism; D004195:Disease Models, Animal; D005069:Evaluation Studies as Topic; D015685:Fusion Proteins, gag-pol / Q000096:biosynthesis; D015658:HIV Infections / Q000378:metabolism*; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D002679:Pan troglodytes; D019713:Receptors, CCR5 / Q000378:metabolism; D013045:Species Specificity; D020079:Terminal Repeat Sequences; D014779:Virus Replication
chemical_list: D015704:CD4 Antigens; D015685:Fusion Proteins, gag-pol; D019713:Receptors, CCR5; D043525:Cytosine Deaminase