Evidence and consequence of porcine endogenous retrovirus recombination.
The genetic nature and biological effects of recombination between porcine endogenous retroviruses (PERV) were studied. An infectious molecular clone was generated from a high-titer, human-tropic PERV isolate, PERV-A 14/220 (B. A. Oldmixon, et al. J. Virol. 76:3045-3048, 2002; T. A. Ericsson et al. Proc. Natl. Acad. Sci. USA 100:6759-6764, 2003). To analyze this sequence and 15 available full-length PERV nucleotide sequences, we developed a sequence comparison program, LOHA(TM) to calculate local sequence homology between two sequences. This analysis determined that PERV-A 14/220 arose by homologous recombination of a PERV-C genome replacing an 850-bp region around the pol-env junction with that of a PERV-A sequence. This 850-bp PERV-A sequence encompasses the env receptor binding domain, thereby conferring a wide host range including human cells. In addition, we determined that multiple regions derived from PERV-C are responsible for the increased infectious titer of PERV-A 14/220. Thus, a single recombination event may be a fast and effective way to generate high-titer, potentially harmful PERV. Further, local homology and phylogenetic analyses between 16 full-length sequences revealed evidence for other recombination events in the past that give rise to other PERV genomes that possess the PERV-A, but not the PERV-B, env gene. These results indicate that PERV-A env is more prone to recombination with heterogeneous backbone genomes than PERV-B env. Such recombination events that generate more active PERV-A appear to occur in pigs rather frequently, which increases the potential risk of zoonotic PERV transmission. In this context, pigs lacking non-human-tropic PERV-C would be more suitable as donor animals for clinical xenotransplantation.
Bartosch
Birke
B
Wohl Virion Centre, Division of Infection of Immunity, University College London, 46 Cleveland St., London W1T 4JF, United Kingdom.
Stefanidis
Dimitrios
D
Myers
Richard
R
Weiss
Robin
R
Patience
Clive
C
Takeuchi
Yasuhiro
Y
D000818:Animals; D002460:Cell Line; D003001:Cloning, Molecular; D019295:Computational Biology / Q000379:methods; D020077:Endogenous Retroviruses / Q000235:genetics* / Q000472:pathogenicity / Q000502:physiology*; D015686:Gene Products, env / Q000235:genetics; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D011533:Proviruses; D011995:Recombination, Genetic; D017422:Sequence Analysis, DNA; D013552:Swine / Q000821:virology; D013556:Swine, Miniature / Q000821:virology*; D014779:Virus Replication
D015686:Gene Products, env