title: Differential sensitivity of porcine endogenous retrovirus to APOBEC3-mediated inhibition.
abstract: Pigs are considered to be suitable xenotransplantation organ donors. However, the risk of pathogen transmission from pigs to humans is a major concern in the transplantation of porcine tissues. The porcine endogenous retroviruses (PERVs) PERV-A, PERV-A/C, and PERV-B can infect human cells, but PERV-C is an ecotropic virus infecting only pig cells. Thus, several strategies have been proposed to reduce PERV transmission in xenograft recipients. Human APOBEC3G (huA3G) is a single-strand DNA cytosine deaminase, which inactivates the coding capacity of the virus by deamination of cDNA cytosines to uracils. This reaction occurs within the (-) DNA strand during reverse transcription, resulting in a G-to-A mutation in the (+) strand. While recent data have shown that PERV-B is severely inhibited by huA3G and porcine A3Z2-Z3 (poA3F) in a pseudotype assay, little is known about PERV-C. Here, we compare the antiretroviral activities of huA3G, huA3F and poA3Z2-Z3 against PERV-C. Our data show that APOBEC3 was packaged into PERV-C particles and inhibited PERV-C replication in a dose-dependent manner. PERV-C infectivity was strongly inhibited by poA3Z2-Z3, but it did not markedly reduce PERV-B infectivity. This suggests that PERV-C Gag interacts efficiently with poA3Z2-Z3. In addition, we constructed stably huA3G- and poA3Z2-Z3-expressing 293-PERV-PK-CIRCE cells (human 293 cells infected with PK15-derived PERVs) to examine whether PERV is resistant to poA3Z2-Z3 in a virus-spreading assay. The stably expressed huA3G and poA3Z2-Z3 were more packaging-competent than transiently expressed APOBEC3 proteins. These results suggest that poA3Z2-Z3 can inhibit PERV replication in a pseudotype assay as well as in a virus-spreading assay.
authors.affiliation: Department of Microbiology, Dankook University, Cheonan, 330-714, Korea.
authors.forename: Sung-Han
authors.initials: SH
authors.lastname: Park
authors.forename: Jin Ha
authors.initials: JH
authors.lastname: Kim
authors.forename: Yong-Tae
authors.initials: YT
authors.lastname: Jung
mesh_terms: D000071480:APOBEC-3G Deaminase; D000818:Animals; D003564:Cytidine Deaminase / Q000235:genetics / Q000276:immunology*; D043525:Cytosine Deaminase / Q000235:genetics / Q000276:immunology*; D020077:Endogenous Retroviruses / Q000145:classification / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D054884:Host-Pathogen Interactions; D006801:Humans; D012190:Retroviridae / Q000145:classification / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D012192:Retroviridae Infections / Q000201:enzymology* / Q000235:genetics / Q000276:immunology / Q000821:virology; D013552:Swine / Q000235:genetics / Q000276:immunology* / Q000821:virology; D014183:Transplantation, Heterologous; D015047:Zoonoses / Q000201:enzymology* / Q000235:genetics / Q000276:immunology / Q000821:virology
chemical_list: C492906:APOBEC3F protein, human; D043525:Cytosine Deaminase; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase