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Differential resistance to cell entry by porcine endogenous retrovirus subgroup A in rodent species

Mattiuzzo, G; Matouskova, M; Takeuchi, Y; (2007) Differential resistance to cell entry by porcine endogenous retrovirus subgroup A in rodent species. Retrovirology , 4 , Article 93. 10.1186/1742-4690-4-93. Green open access

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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. Conclusion: 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.

Type: Article
Title: Differential resistance to cell entry by porcine endogenous retrovirus subgroup A in rodent species
Open access status: An open access version is available from UCL Discovery
DOI: 10.1186/1742-4690-4-93
Publisher version: http://dx.doi.org/10.1186/1742-4690-4-93
Language: English
Additional information: © 2007 Mattiuzzo et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: Ape leukemia-virus, Amino-acid transporter, Gibbon ape, Envelope protein, Surface receptors, Host-range, Infection, Feline, Restriction, Expression
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
URI: https://discovery.ucl.ac.uk/id/eprint/45575
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