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Journal of Virology, July 2007, p. 7048-7060, Vol. 81, No. 13
0022-538X/07/$08.00+0     doi:10.1128/JVI.02714-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Multiple Restrictions of Human Immunodeficiency Virus Type 1 in Feline Cells

Division of Medical Biotechnology, Paul-Ehrlich-Institut, Langen, Germany,¹ Retrovirus Center and Virology Section, Department of Experimental Pathology, University of Pisa, Pisa, Italy,² Department of Genome Modifications and Carcinogenesis, Focus Infection and Cancer, German Cancer Research Centre, Heidelberg, Germany³

Received 8 December 2006/ Accepted 5 April 2007

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 10- to 40-fold.

Published ahead of print on 25 April 2007.

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