title: Differential resistance to cell entry by porcine endogenous retrovirus subgroup A in rodent species.
abstract: BACKGROUND
  The risk of zoonotic infection by porcine endogenous retroviruses (PERV) has been highlighted in the context of pig-to-human xenotransplantation. The use of receptors for cell entry often determines the host range of retroviruses. A human-tropic PERV subgroup, PERV-A, can enter human cells through either of two homologous multitransmembrane proteins, huPAR-1 and huPAR-2. Here, we characterised human PARs and their homologues in the PERV-A resistant rodent species, mouse and rat (muPAR and ratPAR, respectively).
  
  
  RESULTS
  Upon exogenous expression in PERV-A resistant cells, human and rat PARs, but not muPAR, conferred PERV-A sensitivity. Exogenously expressed ratPAR binds PERV-A Env and allows PERV-A infection with equivalent efficiency to that of huPAR-1. Endogenous ratPAR expression in rat cell lines appeared to be too low for PERV-A infection. In contrast, the presence of Pro at position 109 in muPAR was identified to be the determinant for PERV-A resistance. Pro109. was shown to be located in the second extracellular loop (ECL2) and affected PERV-A Env binding to PAR molecules.
  
  
  CONCLUSIONS
  The basis of resistance to PERV-A infection in two rodent species is different. Identification of a single a.a. mutation in muPAR, which is responsible for mouse cell resistance to PERV-A highlighted the importance of ECL-2 for the viral receptor function.
authors: Wohl Virion Centre, Division of Infection and Immunity, University College London, W1T 4JF, London, UK. g.mattiuzzo@ucl.ac.uk
authors: Giada
authors: G
authors: Mattiuzzo
authors: Magda
authors: M
authors: Matouskova
authors: Yasuhiro
authors: Y
authors: Takeuchi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D003001:Cloning, Molecular; D020077:Endogenous Retroviruses / Q000235:genetics / Q000502:physiology*; D015686:Gene Products, env / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D011392:Proline / Q000502:physiology; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011784:Quail; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011991:Receptors, Virus / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012192:Retroviridae Infections; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013552:Swine; D053585:Virus Attachment
chemical_list: D015686:Gene Products, env; D043562:Receptors, G-Protein-Coupled; D011991:Receptors, Virus; D011993:Recombinant Fusion Proteins; D011392:Proline