Cat APOBEC3 genes

APOBEC3 (A3, Apolipoprotein B mRNA-editing catalytic polypeptide 3) genes in the genome of domestic cat (Felis catus) were identified and characterized

To get more insight into the role of APOBEC3 (A3) cytidine deaminases in the species-specific restriction of feline immunodeficiency virus (FIV) of the domestic cat, we tested the A3 proteins present in big cats (puma, lion, tiger, and lynx). These A3 proteins were analyzed for expression and sensitivity to the Vif protein of FIV. While A3Z3s and A3Z2-Z3s inhibited ⌬vif FIV, felid A3Z2s did not show any antiviral activity against ⌬vif FIV or wild-type (wt) FIV. All felid A3Z3s and A3Z2-Z3s were sensitive to Vif of the domestic cat FIV. Vif also induced depletion of felid A3Z2s. Tiger A3s showed a moderate degree of resistance against the Vif-mediated counter defense. These findings may imply that the A3 restriction system does not play a major role to prevent domestic cat FIV transmission to other Felidae. In contrast to the sensitive felid A3s, many nonfelid A3s actively restricted wt FIV replication. To test whether Vif FIV can protect also the distantly related human immunodeficiency virus type 1 (HIV-1), a chimeric HIV-1.Vif FIV was constructed. This HIV-1.Vif FIV was replication competent in nonpermissive feline cells expressing human CD4/CCR5 that did not support the replication of wt HIV-1. We conclude that the replication of HIV-1 in some feline cells is inhibited only by feline A3 restriction factors and the absence of the appropriate receptor or coreceptor.

The APOBEC3 cytidine deaminases are part of the intrinsic defense of cells against retroviruses. Lentiviruses and spumaviruses have evolved essential accessory proteins, Vif and Bet, respectively, which counteract the APOBEC3 proteins. We show here that Bet of the Prototype foamy virus inhibits the antiviral APOBEC3C activity by a mechanism distinct to Vif: Bet forms a complex with APOBEC3C without inducing its degradation. Bet abolished APOBEC3C dimerization as shown by coimmunoprecipitation and cross-linking experiments. These findings implicate a physical interaction between Bet and the APOBEC3C. Subsequently, we identified the Bet interaction domain in human APOBEC3C in the predicted APOBEC3C dimerization site. Taken together, these data support the hypothesis that Bet inhibits incorporation of APOBEC3Cs into retroviral particles. Bet likely achieves this by trapping APOBEC3C protein in complexes rendering them unavailable for newly generated viruses due to direct immobilization. The APOBEC3 (A3)3 genes form part of the intrinsic immunity against retroviruses (1), are under a high adaptive selection (2), and have undergone a unique evolutionary expansion from three to seven genes in primates (APOBEC3A (A3A

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 cellderived 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 ϳ10-to ϳ40-fold.Like many retroviruses, human immunodeficiency virus type 1 (HIV-1) has a very limited host range; spreading replication is seen only in Homo sapiens and by artificial inoculation in the close relative the chimpanzee (Pan troglodytes) (2, 16), preventing the setup of an efficient small animal model for HIV-1 research. Many reasons argue against the widespread use of chimpanzees in research, including the ethical problems involved in the use of an endangered species, budgetary problems, and the very low induction of simian AIDS either from HIV-1 or its ancestor simian immunodeficiency virus cpz (SIVcpz) in infected chimpanzees (25,26,30,57,58,60,63).In general, the tropism of HIV-1 in human tissue is determined by the expression of its receptor protein CD4 together with CCR5 or CXCR4 chemokine receptors. Simian CD4 but not murine CD4 supports entry of HIV-1 (15, 33). HIV-1 entry through receptor-mediated membrane fusion is required for reverse transcription of the viral genomic RNA into a doublestranded DNA molecule. Murine T cells show early postentry restriction of HIV-1 at reverse transcription (3). In simian cells, a related restriction of HIV-1, but not of SIVs (5, 10, 53), involves the simian TRIM5␣ protein, which leads to increased viral uncoating and thereby suppresses reverse transcription (73). Since HIV-1 does not show spreading replication in nonhuman cells, cell type-and t...