Imperial College London
Alternate

Emeritus ProfessorJonathanStoye

Faculty of Medicine, Department of Infectious Disease

Emeritus Professor of Endogenous Retroviruses
 
 
 
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Contact

 

j.stoye Website

 
 
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Location

 

Francis Crick InstituteThe Francis Crick Institute

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Summary

 

Publications

Publication Type
Year
to

137 results found

Schwefel D, Boucherit VC, Christodoulou E, Walker PA, Stoye JP, Bishop KN, Taylor IAet al., 2015, Molecular determinants for recognition of divergent SAMHD1 proteins by the lentiviral accessory protein Vpx, Cell Host and Microbe, Vol: 17, Pages: 489-499, ISSN: 1931-3128

The SAMHD1 triphosphohydrolase inhibits HIV-1 infection of myeloid and resting T cells by depleting dNTPs. To overcome SAMHD1, HIV-2 and some SIVs encode either of two lineages of the accessory protein Vpx that bind the SAMHD1 N or C terminus and redirect the host cullin-4 ubiquitin ligase to target SAMHD1 for proteasomal degradation. We present the ternary complex of Vpx from SIV that infects mandrills (SIVmnd-2) with the cullin-4 substrate receptor, DCAF1, and N-terminal and SAM domains from mandrill SAMHD1. The structure reveals details of Vpx lineage-specific targeting of SAMHD1 N-terminal “degron” sequences. Comparison with Vpx from SIV that infects sooty mangabeys (SIVsmm) complexed with SAMHD1-DCAF1 identifies molecular determinants directing Vpx lineages to N- or C-terminal SAMHD1 sequences. Inspection of the Vpx-DCAF1 interface also reveals conservation of Vpx with the evolutionally related HIV-1/SIV accessory protein Vpr. These data suggest a unified model for how Vpx and Vpr exploit DCAF1 to promote viral replication.

Journal article

Mager DL, Stoye JP, 2015, Mammalian Endogenous Retroviruses, MICROBIOLOGY SPECTRUM, Vol: 3, ISSN: 2165-0497

Journal article

Goldstone DC, Walker PA, Calder LJ, Coombs PJ, Kirkpatrick J, Ball NJ, Hilditch L, Yap MW, Rosenthal PB, Stoye JP, Taylor IAet al., 2014, Structural studies of postentry restriction factors reveal antiparallel dimers that enable avid binding to the HIV-1 capsid lattice, Proceedings of the National Academy of Sciences of the United States of America, Vol: 111, Pages: 9609-9614, ISSN: 0027-8424

Restriction factors (RFs) form important components of host defenses to retroviral infection. The Fv1, Trim5α, and TrimCyp RFs contain N-terminal dimerization and C-terminal specificity domains that target assembled retroviral capsid (CA) proteins enclosing the viral core. However, the molecular detail of the interaction between RFs and their CA targets is unknown. Therefore, we have determined the crystal structure of the B-box and coiled-coil (BCC) region from Trim5α and used small-angle X-ray scattering to examine the solution structure of Trim5α BCC, the dimerization domain of Fv1 (Fv1Ntd), and the hybrid restriction factor Fv1Cyp comprising Fv1NtD fused to the HIV-1 binding protein Cyclophilin A (CypA). These data reveal that coiled-coil regions of Fv1 and Trim5α form extended antiparallel dimers. In Fv1Cyp, two CypA moieties are located at opposing ends, creating a molecule with a dumbbell appearance. In Trim5α, the B-boxes are located at either end of the coiled-coil, held in place by interactions with a helical motif from the L2 region of the opposing monomer. A comparative analysis of Fv1Cyp and CypA binding to a preformed HIV-1 CA lattice reveals how RF dimerization enhances the affinity of interaction through avidity effects. We conclude that the antiparallel organization of the NtD regions of Fv1 and Trim5α dimers correctly positions C-terminal specificity and N-terminal effector domains and facilitates stable binding to adjacent CA hexamers in viral cores.

Journal article

Yap MW, Colbeck E, Ellis SA, Stoye JPet al., 2014, Evolution of the retroviral restriction gene Fv1: inhibition of non-MLV retroviruses, PLoS Pathogens, Vol: 10, Pages: 1-14, ISSN: 1553-7366

Fv1 is the prototypic restriction factor that protects against infection by the murine leukemia virus (MLV). It was first identified in cells that were derived from laboratory mice and was found to be homologous to the gag gene of an endogenous retrovirus (ERV). To understand the evolution of the host restriction gene from its retroviral origins, Fv1s from wild mice were isolated and characterized. Most of these possess intact open reading frames but not all restricted N-, B-, NR-or NB-tropic MLVs, suggesting that other viruses could have played a role in the selection of the gene. The Fv1s from Mus spretus and Mus caroli were found to restrict equine infectious anemia virus (EIAV) and feline foamy virus (FFV) respectively, indicating that Fv1 could have a broader target range than previously thought, including activity against lentiviruses and spumaviruses. Analyses of the Fv1 sequences revealed a number of residues in the C-terminal region that had evolved under positive selection. Four of these selected residues were found to be involved in the novel restriction by mapping studies. These results strengthen the similarities between the two capsid binding restriction factors, Fv1 and TRIM5α, which support the hypothesis that Fv1 defended mice against waves of retroviral infection possibly including non-MLVs as well as MLVs.

Journal article

Schwefel D, Groom HCT, Boucherit VC, Christodoulou E, Walker PA, Stoye JP, Bishop KN, Taylor IAet al., 2014, Structural basis of lentiviral subversion of a cellular protein degradation pathway, NATURE, Vol: 505, Pages: 234-+, ISSN: 0028-0836

Journal article

Sanz-Ramos M, Stoye JP, 2013, Capsid-binding retrovirus restriction factors: discovery, restriction specificity and implications for the development of novel therapeutics, JOURNAL OF GENERAL VIROLOGY, Vol: 94, Pages: 2587-2598, ISSN: 0022-1317

Journal article

Yap MW, Stoye JP, 2013, Apparent effect of rabbit endogenous lentivirus type K acquisition on retrovirus restriction by lagomorph Trim5αs, PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES, Vol: 368, ISSN: 0962-8436

Journal article

Young GR, Stoye JP, Kassiotis G, 2013, Are human endogenous retroviruses pathogenic? An approach to testing the hypothesis, BIOESSAYS, Vol: 35, Pages: 794-803, ISSN: 0265-9247

Journal article

Ohkura S, Stoye JP, 2013, A Comparison of Murine Leukemia Viruses That Escape from Human and Rhesus Macaque TRIM5αs, JOURNAL OF VIROLOGY, Vol: 87, Pages: 6455-6468, ISSN: 0022-538X

Journal article

Weiss RA, Stoye JP, 2013, Our Viral Inheritance, SCIENCE, Vol: 340, Pages: 820-821, ISSN: 0036-8075

Journal article

Goldstone DC, Flower TG, Ball NJ, Sanz-Ramos M, Yap MW, Ogrodowicz RW, Stanke N, Reh J, Lindemann D, Stoye JP, Taylor IAet al., 2013, A Unique Spumavirus Gag N-terminal Domain with Functional Properties of Orthoretroviral Matrix and Capsid, PLOS PATHOGENS, Vol: 9, ISSN: 1553-7366

Journal article

Young GR, Eksmond U, Salcedo R, Alexopoulou L, Stoye JP, Kassiotis Get al., 2012, Resurrection of endogenous retroviruses in antibody-deficient mice, NATURE, Vol: 491, Pages: 774-+, ISSN: 0028-0836

Journal article

Stoye JP, 2012, Studies of endogenous retroviruses reveal a continuing evolutionary saga, NATURE REVIEWS MICROBIOLOGY, Vol: 10, Pages: 395-406, ISSN: 1740-1526

Journal article

Young GR, Ploquin MJ-Y, Eksmond U, Wadwa M, Stoye JP, Kassiotis Get al., 2012, Negative Selection by an Endogenous Retrovirus Promotes a Higher-Avidity CD4<SUP>+</SUP> T Cell Response to Retroviral Infection, PLOS PATHOGENS, Vol: 8, ISSN: 1553-7366

Journal article

Young GR, Kassiotis G, Stoye JP, 2012, <i>Emv2</i>, the only endogenous ecotropic murine leukemia virus of C57BL/6J mice, RETROVIROLOGY, Vol: 9

Journal article

Yap MW, Stoye JP, 2012, TRIM PROTEINS AND THE INNATE IMMUNE RESPONSE TO VIRUSES, TRIM/RBCC PROTEINS, Vol: 770, Pages: 93-104, ISSN: 0065-2598

Journal article

Goldstone DC, Ennis-Adeniran V, Hedden JJ, Groom HCT, Rice GI, Christodoulou E, Walker PA, Kelly G, Haire LF, Yap MW, de Carvalho LPS, Stoye JP, Crow YJ, Taylor IA, Webb Met al., 2011, HIV-1 restriction factor SAMHD1 is a deoxynucleoside triphosphate triphosphohydrolase, NATURE, Vol: 480, Pages: 379-U134, ISSN: 0028-0836

Journal article

Gray ER, Illingworth CJR, Coffin JM, Stoye JPet al., 2011, Binding of more than one Tva800 molecule is required for ASLV-A entry, RETROVIROLOGY, Vol: 8, ISSN: 1742-4690

Journal article

Tuke PW, Tettmar KI, Tamuri A, Stoye JP, Tedder RSet al., 2011, PCR master mixes harbour murine DNA sequences. caveat emptor!, PLoS One, Vol: 6, Pages: 1-6, ISSN: 1932-6203

BackgroundXMRV is the most recently described retrovirus to be found in Man, firstly in patients with prostate cancer (PC) and secondly in 67% of patients with chronic fatigue syndrome (CFS) and 3.7% of controls. Both disease associations remain contentious. Indeed, a recent publication has concluded that “XMRV is unlikely to be a human pathogen”. Subsequently related but different polytropic MLV (pMLV) sequences were also reported from the blood of 86.5% of patients with CFS. and 6.8% of controls. Consequently we decided to investigate blood donors for evidence of XMRV/pMLV.Methodology/Principal FindingsTesting of cDNA prepared from the whole blood of 80 random blood donors, generated gag PCR signals from two samples (7C and 9C). These had previously tested negative for XMRV by two other PCR based techniques. To test whether the PCR mix was the source of these sequences 88 replicates of water were amplified using Invitrogen Platinum Taq (IPT) and Applied Biosystems Taq Gold LD (ABTG). Four gag sequences (2D, 3F, 7H, 12C) were generated with the IPT, a further sequence (12D) by ABTG re-amplification of an IPT first round product. Sequence comparisons revealed remarkable similarities between these sequences, endogeous MLVs and the pMLV sequences reported in patients with CFS.Conclusions/SignificanceMethodologies for the detection of viruses highly homologous to endogenous murine viruses require special caution as the very reagents used in the detection process can be a source of contamination and at a level where it is not immediately apparent. It is suggested that such contamination is likely to explain the apparent presence of pMLV in CFS.

Journal article

Rahm N, Yap M, Snoeck J, Zoete V, Munoz M, Radespiel U, Zimmermann E, Michielin O, Stoye JP, Ciuffi A, Telenti Aet al., 2011, Unique Spectrum of Activity of Prosimian TRIM5α against Exogenous and Endogenous Retroviruses, JOURNAL OF VIROLOGY, Vol: 85, Pages: 4173-4183, ISSN: 0022-538X

Journal article

Hilditch L, Matadeen R, Goldstone DC, Rosenthal PB, Taylor IA, Stoye JPet al., 2011, Ordered assembly of murine leukemia virus capsid protein on lipid nanotubes directs specific binding by the restriction factor, Fv1, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 108, Pages: 5771-5776, ISSN: 0027-8424

Journal article

Ohkura S, Goldstone DC, Yap MW, Holden-Dye K, Taylor IA, Stoye JPet al., 2011, Novel Escape Mutants Suggest an Extensive TRIM5α Binding Site Spanning the Entire Outer Surface of the Murine Leukemia Virus Capsid Protein, PLOS PATHOGENS, Vol: 7, ISSN: 1553-7374

Journal article

McNab FW, Rajsbaum R, Stoye JP, O'Garra Aet al., 2011, Tripartite-motif proteins and innate immune regulation, CURRENT OPINION IN IMMUNOLOGY, Vol: 23, Pages: 46-56, ISSN: 0952-7915

Journal article

Stoye JP, Silverman RH, Boucher CA, Le Grice SFJet al., 2010, The xenotropic murine leukemia virus-related retrovirus debate continues at first international workshop, RETROVIROLOGY, Vol: 7

Journal article

Goldstone DC, Yap MW, Robertson LE, Haire LF, Taylor WR, Katzourakis A, Stoye JP, Taylor IAet al., 2010, Structural and Functional Analysis of Prehistoric Lentiviruses Uncovers an Ancient Molecular Interface, CELL HOST & MICROBE, Vol: 8, Pages: 248-259, ISSN: 1931-3128

Journal article

Groom HCT, Yap MW, Galao RP, Neil SJD, Bishop KNet al., 2010, Susceptibility of xenotropic murine leukemia virus-related virus (XMRV) to retroviral restriction factors, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 107, Pages: 5166-5171, ISSN: 0027-8424

Journal article

Groom HCT, Boucherit VC, Makinson K, Randal E, Baptista S, Hagan S, Gow JW, Mattes FM, Breuer J, Kerr JR, Stoye JP, Bishop KNet al., 2010, Absence of xenotropic murine leukaemia virus-related virus in UK patients with chronic fatigue syndrome, RETROVIROLOGY, Vol: 7, ISSN: 1742-4690

Journal article

Coffin JM, Stoye JP, 2009, A New Virus for Old Diseases?, SCIENCE, Vol: 326, Pages: 530-531, ISSN: 0036-8075

Journal article

Stoye JP, 2009, Proviral protein provides placental function, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 106, Pages: 11827-11828, ISSN: 0027-8424

Journal article

Mortuza GB, Goldstone DC, Pashley C, Haire LF, Palmarini M, Taylor WR, Stoye JP, Taylor IAet al., 2009, Structure of the Capsid Amino-Terminal Domain from the Betaretrovirus, Jaagsiekte Sheep Retrovirus, JOURNAL OF MOLECULAR BIOLOGY, Vol: 386, Pages: 1179-1192, ISSN: 0022-2836

Journal article

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