Faculty of Biological Sciences

Prof Mark Harris

BSc, Plymouth, PhD 1987, Glasgow
Professor of Virology
School of Molecular and Cellular Biology

Background: 1987-1988, Post-doctoral position with Dr Possee, NERC Institute of Virology, Oxford; 1988-1993 PostDoctoral Research Fellow, MRC Retrovirus Research Laboratory, Department of Veterinary Pathology, Glasgow; 1993-1998 MRC Senior Research Fellowship, MRC Retrovirus Laboratory, Glasgow, Department of Microbiology, University of Leeds.

Contact:  Garstang 8.59, +44(0) 113 34 35632, email address for  

You can read more about Prof Harris's interests here:
www.astbury.leeds.ac.uk/People/staffpage.php?StaffID=MH


Research Interests

Virus-host interactions in hepatitis C virus and HIV-1

Studies on the replication and assembly of hepatitis C virus

Hepatitis C virus is an important human pathogen that infects an estimated 170 million people worldwide. My laboratory is interested in understanding the molecular mechanisms by which this virus replicates its genome and assembles into new virus particles, with a particular focus on the virus-host interactions that underpin these processes. The ultimate goal of this research is to identify new targets for the development of novel antivirals. Work in my laboratory is funded mainly by the Wellcome Trust, principally via a recent Senior Investigator Award.

Specific projects include:

1) Functional studies on the non-structural NS5A protein. 

NS5A is a phosphoprotein that plays as yet undefined but essential roles in both genome replication and virus assembly. We are using a combination of techniques to investigate these roles, for example mutagenesis to define key residues, protein-protein interaction analysis to identify cellular (and viral) partners and mass spectrometry to identify phosphorylation sites. We are also investigating the interaction of NS5A with viral RNA, with the aim of identifying RNA–binding motifs within NS5A and defining the RNA sequences that are bound by the protein. 

NS5A also perturbs cellular physiology by modulating a number of signalling pathways, eg MAP kinases, PI3K. In this regard we have a particular interest in the interactions of NS5A with cellular SH3 domain containing proteins such as Src-family kinases. These interactions mediate (amongst others) inhibition of a pro-apoptotic potassium channel (Kv2.1), rendering infected cells resistant to oxidative stress induced apoptosis.

2) Understanding the structure and composition of the RNA replication complex. 

We are using both proteomic and imaging techniques to probe the multiprotein complex that replicates the viral genome. For example – purifying the nascent RNA from infected cells and identifying the associated proteins by mass spectrometry and genetically tagging the virus to enable either high resolution EM or fluorescent imaging.

3) Application of structure-based drug design to develop new HCV therapeutics.

In collaboration with Prof Colin Fishwick (Chemistry) we are exploiting the existing structural information about HCV non-structural proteins (in particular NS2 and NS5A) to identify candidate antivirals. These will be tested using established methodologies (sub-genomic replicons, infectious virus assays) and then subject to iterative SAR to optimise their potential to inhibit virus replication.

HIV Nef studies

In addition to studies on HCV, we are using structure-based drug design to design inhibitors of the HIV-1 Nef protein. Nef is a key protein in HIV pathogenesis and we have determined the crystal structure of the full-length myristoylated HIV-1 Nef (in collaboration with Dr Jo Jaeger – currently in Albany, NY).  These studies have identified compounds that have been assayed using FACS to demonstrate inhibition of Nef induced CD4 and MHC-I down-modulation, and shown by ITC to bind to Nef.

We are part of the Virology and Structural Molecular Biology groups
Research in my laboratory is funded by the Wellcome Trust, studentships are funded by the Wellcome Trust and  BBSRC.
 

Faculty Research and Innovation



Studentship information

Undergraduate project topics:

  • Virus-host interactions in hepatitis C virus and HIV-1.
  • Replication of hepatitis C virus.

See also:

Modules managed

MICR2121 - Molecular Virology
MICR2222 - Medical Virology

Modules taught

BIOC3221/22/BIOL3210/MICR3211 a - ATU - World of Viruses
BIOL2301 - Intermediate Skills for Biological Sciences
BIOL2301/03/05/MICR2320 - Skills for Biol Sci, Biosciences and Microbiology
BIOL3305/3400/BIOC3303/MICR3325 - BIOL/BIOC/MICR advanced skills
BIOL5171M - Infectious & Non-infectious Diseases
BIOL5312M - Bioimaging
BIOL5371M - Research Planning and Scientific Communication
BIOL5373M - Protein Engineering Laboratory Project
BIOL5382M - Extended Research Project
BMSC2210 - Chemotherapy
MICR2121 - Molecular Virology
MICR2222 - Medical Virology
MICR3211 - Advanced Topics in Microbiology 2
MICR3325 - Skills for Microbiologists 3

Committees

Member of Masters Taught Student Education Committee (Co-opted member)

Centre membership: The Astbury Centre for Structural Molecular Biology

Group Leader Prof Mark Harris  (Professor of Virology)

Virus-host interactions in hepatitis C virus and HIV-1 

Dr Niluka Goonawardane  (Research Fellow)

Dr Roland Remenyi  (Research Fellow)

Developing research tools to visualise viral infection by advanced microscopy 

Mr Carsten Zothner  (Technician)


Postgraduates

Yanni Gao (Primary supervisor) 50% FTE
Lorna Kelly (Primary supervisor) 100% FTE
Joseph Lattimer (Primary supervisor) 50% FTE
Siu Yi Lee (Primary supervisor) 50% FTE
Raymond Li (Primary supervisor) 50% FTE
Grace Roberts (Primary supervisor) 50% FTE
Chunhong Yin (Primary supervisor) 50% FTE
Lauren Branfield (Co-supervisor) 33% FTE
Emily Levitt (Co-supervisor) 50% FTE
Eleni-Anna Loundras (Co-supervisor) 50% FTE
Ghada Shawli (Co-supervisor) 33% FTE
Beatriz Solis Cordova (Co-supervisor) 50% FTE

Remenyi R, Roberts GC, Zothner C, Merits A, Harris M SNAP-Tagged Chikungunya Virus Replicons Improve Visualisation of Non-Structural Protein 3 by Fluorescence Microscopy Scientific Reports 7 -, 2017
DOI:10.1038/s41598-017-05820-0
View abstract

Goonawardane N, Gebhardt A, Bartlett C, Pichlmair A, Harris M Phosphorylation of Serine 225 in Hepatitis C Virus NS5A Regulates Protein-Protein Interactions. J Virol 91 -, 2017
DOI:10.1128/JVI.00805-17
View abstract

Campos GRF, Bittar C, Jardim ACG, Shimizu JF, Batista MN, Paganini ER, Assis LRD, Bartlett C, Harris M, Bolzani VDS, Regasini LO, Rahal P Hepatitis C virus in vitro replication is efficiently inhibited by acridone Fac4 Journal of General Virology 98 1693-1701, 2017
DOI:10.1099/jgv.0.000808
View abstract

Loundras EA, Herod MR, Harris M, Stonehouse NJ Foot-and-mouth disease virus genome replication is unaffected by inhibition of type III phosphatidylinositol-4-kinases Journal of General Virology 97 2221-2230, 2016
DOI:10.1099/jgv.0.000527
View abstract

Mankouri J, Walter C, Stewart H, Bentham M, Park WS, Heo WD, Fukuda M, Griffin S, Harris M Release of Infectious Hepatitis C Virus from Huh7 Cells Occurs via a trans-Golgi Network-to-Endosome Pathway Independent of Very-Low-Density Lipoprotein Secretion. J Virol 90 7159-7170, 2016
DOI:10.1128/JVI.00826-16
View abstract

Saundh BK, Baker R, Harris M, Hale A A prospective study of renal transplant recipients reveals an absence of primary JC polyomavirus infections JOURNAL OF CLINICAL VIROLOGY 77 101-105, 2016
DOI:10.1016/j.jcv.2016.02.015

Stewart H, Bingham RJ, White SJ, Dykeman EC, Zothner C, Tuplin AK, Stockley PG, Twarock R, Harris M Identification of novel RNA secondary structures within the hepatitis C virus genome reveals a cooperative involvement in genome packaging Scientific Reports 6 -, 2016
DOI:10.1038/srep22952
View abstract

Mohl B, Bartlett C, Mankouri J, Harris M Early events in the generation of autophagosomes are required for the formation of membrane structures involved in hepatitis C virus genome replication Journal of General Virology 97 680-693, 2016
DOI:10.1099/jgv.0.000387
View abstract

Shaw J, Harris M, Fishwick CWG Identification of a lead like inhibitor of the hepatitis C virus non-structural NS2 autoprotease Antiviral Research 124 54-60, 2015
DOI:10.1016/j.antiviral.2015.10.001
View abstract

Saundh B, Baker R, Harris M, Hale A Early JCV infection protects against BKV infection in renal transplant recipients, 2015
DOI:10.1016/j.jcv.2015.07.195

Brennan B, Weber F, Kormelink R, Schnettler E, Bouloy M, Failloux AB, Weaver SC, Fazakerley JK, Fragkoudis R, Harris M, Barr JN, Palese P, García-Sastre A, Dalziel RG, Dutia BM, Lowen AC, Steel J, Randall RE, Paul Duprex W, Rice CM, Tesh RB, Murphy FA, Ebihara H, Vasconcelos PFC, Nunes MR, Fooks AR, Smith GL, Goodfellow I, Pappu HR, Lamb RA, Paterson RG, Higgs S, Vanlandingham DL, Dietzgen RG, Stephen Lodmell J, Nichol ST, Daly J, UllmanDE, Plyusnin A, Plyusnina A, Efstathiou S, Hewson R, Tordo N, Cherry S, Boutell C, Hosie MJ, Murcia PR, Neil JC, Palmarini M, Patel AH, Willett BJ, Kohl A, McLauchlan J In memoriam--Richard M. Elliott (1954-2015) The Journal of general virology 96 1975-1978, 2015
DOI:10.1099/jgv.0.000241

Igloi Z, Kazlauskas A, Saksela K, Macdonald A, Mankouri J, Harris M Hepatitis C virus NS5A protein blocks epidermal growth factor receptor degradation via a proline motif- dependent interaction Journal of General Virology 96 2133-2144, 2015
DOI:10.1099/vir.0.000145
View abstract

Stewart H, Bartlett C, Ross-Thriepland D, Shaw J, Griffin S, Harris M A novel method for the measurement of hepatitis C virus infectious titres using the IncuCyte ZOOM and its application to antiviral screening Journal of Virological Methods 218 59-65, 2015
DOI:10.1016/j.jviromet.2015.03.009
View abstract

Ross-Thriepland D, Harris M Hepatitis C virus NS5A: enigmatic but still promiscuous 10 years on! Journal of General Virology 96 727-738, 2015
DOI:10.1099/jgv.0.000009
View abstract

Igloi Z, Mohl BP, Lippiat JD, Harris M, Mankouri J Requirement for chloride channel function during the hepatitis C virus life cycle Journal of Virology 89 4023-4029, 2015
DOI:10.1128/JVI.02946-14
View abstract

Ross-Thriepland D, Mankouri J, Harris M Serine phosphorylation of the hepatitis C virus NS5A protein controls the establishment of replication complexes Journal of Virology 89 3123-3135, 2015
DOI:10.1128/JVI.02995-14
View abstract

Jardim ACG, Igloi Z, Shimizu JF, Santos VAFFM, Felippe LG, Mazzeu BF, Amako Y, Furlan M, Harris M, Rahal P Natural compounds isolated from Brazilian plants are potent inhibitors of hepatitis C virus replication in vitro Antiviral Research 115 39-47, 2015
DOI:10.1016/j.antiviral.2014.12.018
View abstract

Carneiro B, Braga ACS, Batista MN, Harris M, Rahal P Evaluation of canonical siRNA and Dicer substrate RNA for inhibition of hepatitis C virus genome replication - a comparative study PLoS One 10 -, 2015
DOI:10.1371/journal.pone.0117742
View abstract

Amako Y, Munakata T, Kohara M, Siddiqui A, Peers C, Harris M Hepatitis C virus attenuates mitochondrial lipidβ-oxidation by downregulating mitochondrial trifunctional-protein expression Journal of Virology 89 4092-4101, 2015
DOI:10.1128/JVI.01653-14
View abstract

Shaw J, Fishwick C, Harris M Epoxide based inhibitors of the hepatitis C virus non-structural 2 autoprotease Antiviral Research 117 20-26, 2015
DOI:10.1016/j.antiviral.2015.02.005
View abstract

Foster TL, Thompson GS, Kalverda AP, Kankanala J, Bentham M, Wetherill LF, Thompson J, Barker AM, Clarke D, Noerenberg M, Pearson AR, Rowlands DJ, Homans SW, Harris M, Foster R, Griffin S Structure-guided design affirms inhibitors of hepatitis C virus p7 as a viable class of antivirals targeting virion release. Hepatology 59 408-422, 2014
DOI:10.1002/hep.26685
View abstract

Ross-Thriepland D, Harris M Insights into the complexity and functionality of hepatitis C virus NS5A phosphorylation. Journal of Virology 88 1421-1432, 2014
DOI:10.1128/JVI.03017-13
View abstract

Atkins E, Harris M, Griffin S, Tatineni R, Li H, Gretch D The stability of secreted, acid-labile H77/JFH-1 hepatitis C virus (HCV) particles is altered by patient isolate genotype 1a p7 sequences Virology 448 117-124, 2014
DOI:10.1016/j.virol.2013.10.003
View abstract

Hamed MR, Brown RJP, Zothner C, Urbanowicz RA, Mason CP, Krarup A, McClure CP, Irving WL, Ball JK, Harris M, Hickling TP, Tarr AW Recombinant Human L-Ficolin Directly Neutralizes Hepatitis C Virus Entry JOURNAL OF INNATE IMMUNITY 6 676-684, 2014
DOI:10.1159/000362209

Stewart H, Walter C, Jones D, Lyons S, Simmonds P, Harris M The non-primate hepacivirus 5 ' untranslated region possesses internal ribosomal entry site activity Journal of General Virology 94 2657-2663, 2013
DOI:10.1099/vir.0.055764-0
View abstract

Amako Y, Igloi Z, Mankouri J, Kazlauskas A, Saksela K, Dallas M, Peers C, Harris M Hepatitis C virus NS5A inhibits mixed lineage kinase 3 to block apoptosis. Journal of Biological Chemistry 288 24753-24763, 2013
DOI:10.1074/jbc.M113.491985
View abstract

Ross-Thriepland D, Amako Y, Harris M The C terminus of NS5A domain II is a key determinant of hepatitis C virus genome replication, but is not required for virion assembly and release. Journal of General Virology 94 1009-1018, 2013
DOI:10.1099/vir.0.050633-0
View abstract

Saundh BK, Baker R, Harris M, Welberry Smith MP, Cherukuri A, Hale A Early BK polyomavirus (BKV) reactivation in donor kidney is a risk factor for development of BKV-associated nephropathy. J Infect Dis 207 137-141, 2013
DOI:10.1093/infdis/jis642
View abstract

Mohl B-P, Tedbury PR, Griffin S, Harris M Hepatitis C virus-induced autophagy is independent of the unfolded protein response. J Virol 86 10724-10732, 2012
DOI:10.1128/JVI.01667-12
View abstract

Wetherill LF, Holmes KK, Verow M, Müller M, Howell G, Harris M, Fishwick C, Stonehouse N, Foster R, Blair GE, Griffin S, Macdonald A High-risk human papillomavirus E5 oncoprotein displays channel-forming activity sensitive to small-molecule inhibitors. J Virol 86 5341-5351, 2012
DOI:10.1128/JVI.06243-11
View abstract

Li H, Atkins E, Bruckner J, McArdle S, Qiu WC, Thomassen LV, Scott J, Shuhart MC, Livingston S, Townshend-Bulson L, McMahon BJ, Harris M, Griffin S, Gretch DR Genetic and functional heterogeneity of the hepatitis C virus p7 ion channel during natural chronic infection. Virology 423 30-37, 2012
DOI:10.1016/j.virol.2011.11.011
View abstract

Taylor A, Jackson BR, Noerenberg M, Hughes DJ, Boyne JR, Verow M, Harris M, Whitehouse A Mutation of a C-Terminal Motif Affects Kaposi's Sarcoma-Associated Herpesvirus ORF57 RNA Binding, Nuclear Trafficking, and Multimerization J VIROL 85 7881-7891, 2011
DOI:10.1128/JVI.00138-11

Foster TL, Verow M, Wozniak AL, Bentham MJ, Thompson J, Atkins E, Weinman SA, Fishwick C, Foster R, Harris M, Griffin S Resistance Mutations Define Specific Antiviral Effects for Inhibitors of the Hepatitis C Virus p7 Ion Channel HEPATOLOGY 54 79-90, 2011
DOI:10.1002/hep.24371

Mankouri J, Harris M Viruses and the fuel sensor: the emerging link between AMPK and virus replication REV MED VIROL 21 205-212, 2011
DOI:10.1002/rmv.687

Foster TL, Gallay P, Stonehouse NJ, Harris M Cyclophilin A Interacts with Domain II of Hepatitis C Virus NS5A and Stimulates RNA Binding in an Isomerase-Dependent Manner J VIROL 85 7460-7464, 2011
DOI:10.1128/JVI.00393-11

Dallas ML, Boyle JP, Milligan CJ, Sayer R, Kerrigan TL, McKinstry C, Lu PY, Mankouri J, Harris M, Scragg JL, Pearson HA, Peers C Carbon monoxide protects against oxidant-induced apoptosis via inhibition of K(v)2.1 FASEB J 25 1519-1530, 2011
DOI:10.1096/fj.10-173450

Nandasoma U, McCormick C, Griffin S, Harris M Nucleotide requirements at positions +1 to +4 for the initiation of hepatitis C virus positive-strand RNA synthesis J GEN VIROL 92 1082-1086, 2011
DOI:10.1099/vir.0.028423-0

Tedbury P, Welbourn S, Pause A, King B, Griffin S, Harris M The subcellular localization of the hepatitis C virus non-structural protein NS2 is regulated by an ion channel-independent function of the p7 protein Journal of General Virology 92 819-830, 2011
DOI:10.1099/vir.0.027441-0
View abstract

Foster TL, Verow M, Wozniak M, Bentham M, Thompson J, Atkins E, Weinman S, Fishwick CWG, Foster RJ, Harris M, Griffin S Resistance mutations define specific antiviral effects for inhibitors of the hepatitis C virus (HCV) p7 ion channel Hepatology 54 79-90, 2011

Gilliver AN, Griffin S, Harris M Identification of a novel phosphorylation site in hepatitis C virus NS5A Journal of General Virology 91 2428-2432, 2010
DOI:10.1099/vir.0.023614-0
View abstract

Foster TL, Belyaeva T, Stonehouse NJ, Pearson AR, Harris M All Three Domains of the Hepatitis C Virus Nonstructural NS5A Protein Contribute to RNA Binding J VIROL 84 9267-9277, 2010
DOI:10.1128/JVI.00616-10

Wozniak AL, Griffin S, Rowlands D, Harris M, Yi MK, Lemon SM, Weinman SA Intracellular Proton Conductance of the Hepatitis C Virus p7 Protein and Its Contribution to Infectious Virus Production PLoS Pathogens 6 -, 2010
DOI:10.1371/journal.ppat.1001087
View abstract

Saundh BK, Tibble S, Baker R, Sasnauskas K, Harris M, Hale A Different patterns of BK and JC polyomavirus reactivation following renal transplantation J CLIN PATHOL 63 714-718, 2010
DOI:10.1136/jcp.2009.074864

Carter SD, Dent KC, Atkins E, Foster TL, Verow M, Gorny P, Harris M, Hiscox JA, Ranson NA, Griffin S, Barr JN Direct visualization of the small hydrophobic protein of human respiratory syncytial virus reveals the structural basis for membrane permeability FEBS LETT 584 2786-2790, 2010
DOI:10.1016/j.febslet.2010.05.006

Mankouri J, Tedbury PR, Gretton S, Hughes ME, Griffin SDC, Dallas ML, Green KA, Hardie DG, Peers C, Harris M Enhanced hepatitis C virus genome replication and lipid accumulation mediated by inhibition of AMP-activated protein kinase P NATL ACAD SCI USA 107 11549-11554, 2010
DOI:10.1073/pnas.0912426107

Gretton S, Hughes M, Harris M Hepatitis C virus RNA replication is regulated by Ras-Erk signalling J GEN VIROL 91 671-680, 2010
DOI:10.1099/vir.0.016899-0

Mankouri J, Fragkoudis R, Richards KH, Wetherill LF, Harris M, Kohl A, Elliott RM, Macdonald A Optineurin Negatively Regulates the Induction of IFN beta in Response to RNA Virus Infection PLOS PATHOG 6 -, 2010
DOI:10.1371/journal.ppat.1000778

Milward A, Mankouri J, Harris M Hepatitis C virus NS5A protein interacts with beta-catenin and stimulates its transcriptional activity in a phosphoinositide-3 kinase-dependent fashion J GEN VIROL 91 373-381, 2010
DOI:10.1099/vir.0.015305-0

Corless L, Crump CM, Griffin SDC, Harris M Vps4 and the ESCRT-III complex are required for the release of infectious hepatitis C virus particles J GEN VIROL 91 362-372, 2010
DOI:10.1099/vir.0.017285-0

Gamlen T, Richards KH, Mankouri J, Hudson L, McCauley J, Harris M, Macdonald A Expression of the NS3 protease of cytopathogenic bovine viral diarrhea virus results in the induction of apoptosis but does not block activation of the beta interferon promoter J GEN VIROL 91 133-144, 2010
DOI:10.1099/vir.0.016170-0

Foster TL, Tedbury PR, Pearson AR, Harris M A comparative analysis of the fluorescence properties of the wild-type and active site mutants of the hepatitis C virus autoprotease NS2-3 BBA-PROTEINS PROTEOM 1804 212-222, 2010
DOI:10.1016/j.bbapap.2009.10.006

Hughes M, Gretton S, Shelton H, Brown DD, McCormick CJ, Angus AGN, Patel AH, Griffin S, Harris M A Conserved Proline between Domains II and III of Hepatitis C Virus NS5A Influences both RNA Replication and Virus Assembly J VIROL 83 10788-10796, 2009
DOI:10.1128/JVI.02406-08

Mankouri J, Dallas ML, Hughes ME, Griffin SDC, Macdonald A, Peers C, Harris M Suppression of a pro-apoptotic K+ channel as a mechanism for hepatitis C virus persistence P NATL ACAD SCI USA 106 15903-15908, 2009
DOI:10.1073/pnas.0906798106

StGelais C, Foster TL, Verow M, Atkins E, Fishwick CWG, Rowlands D, Harris M, Griffin S Determinants of Hepatitis C Virus p7 Ion Channel Function and Drug Sensitivity Identified In Vitro J VIROL 83 7970-7981, 2009
DOI:10.1128/JVI.00521-09

Hughes M, Griffin S, Harris M Domain III of NS5A contributes to both RNA replication and assembly of hepatitis C virus particles J GEN VIROL 90 1329-1334, 2009
DOI:10.1099/vir.0.009332-0

Tedbury P, Harris M Hepatitis C Virus VIRAL PROTEASES AND ANTIVIRAL PROTEASE INHIBITOR THERAPY: PROTEASES IN BIOLOGY AND DISEASE 8 47-69, 2009
DOI:10.1007/978-90-481-2348-3_3

Griffin S, StGelais C, Owsianka AM, Patel AH, Rowlands D, Harris M Genotype-Dependent Sensitivity of Hepatitis C Virus to Inhibitors of the p7 Ion Channel HEPATOLOGY 48 1779-1790, 2008
DOI:10.1002/hep.22555

Griffin S, Trowbridge R, Thommes P, Parry N, Rowlands D, Harris M, Bright H Chimeric GB virus B genomes containing hepatitis C virus p7 are infectious in vivo J HEPATOL 49 908-915, 2008
DOI:10.1016/j.jhep.2008.07.020

Mankouri J, Griffin S, Harris M The hepatitis C virus non-structural protein NS5A alters the trafficking profile of the epidermal growth factor receptor TRAFFIC 9 1497-1509, 2008
DOI:10.1111/j.1600-0854.2008.00779.x

Mankouri J, Milward A, Pryde KR, Warter L, Martin A, Harris M A comparative cell biological analysis reveals only limited functional homology between the NS5A proteins of hepatitis C virus and GB virus B J GEN VIROL 89 1911-1920, 2008
DOI:10.1099/vir.0.2008/001131-0

Shelton H, Harris M Hepatitis C virus NS5A protein binds the SH3 domain of the Fyn tyrosine kinase with high affinity: mutagenic analysis of residues within the SH3 domain that contribute to the interaction VIROLOGY JOURNAL 5 -, 2008
DOI:10.1186/1743-422X-5-24

StGelais C, Tuthill TJ, Clarke DS, Rowlands DJ, Harris M, Griffin S Inhibition of hepatitis C virus p7 membrane channels in a liposome-based assay system. Antiviral Res 76 48-58, 2007
DOI:10.1016/j.antiviral.2007.05.001
View abstract

Willberg CB, Ward SM, Clayton RF, Naoumov NV, McCormick C, Proto S, Harris M, Patel AH, Klenerman P Protection of Hepatocytes from Cytotoxic T Cell Mediated Killing by Interferon-Alpha PLoS One 2 -, 2007
DOI:10.1371/journal.pone.0000791
View abstract

Tedbury PR, Harris M Characterisation of the role of zinc in the hepatitis C virus NS2/3 auto-cleavage and NS3 protease activities J MOL BIOL 366 1652-1660, 2007
DOI:10.1016/j.jmb.2006.12.062

Clarke D, Griffin SDC, Beales L, Gelais CS, Burgess S, Harris MPG, Rowlands DJ Evidence for the formation of a heptameric ion channel complex by the hepatitis C virus p7 protein in vitro Journal of Biological Chemistry 281 37057-37068, 2006
DOI:10.1074/jbc.M602434200
View abstract

McCormick CJ, Maucourant S, Griffin SDC, Rowlands DJ, Harris MPG Tagging of NS5A expressed from a functional hepatitis C virus replicon Journal of General Virology 87 635-640, 2006
DOI:10.1099/vir.0.81553-0
View abstract

Bentham MJ, Mazaleyrat SL, Harris MPG Role of myristoylation and N-terminal basic residues in membrane association of the human immunodeficiency virus type 1 Nef protein Journal of General Virology 87 563-571, 2006
DOI:10.1099/vir.0.81200-0
View abstract

McCormick CJ, Brown D, Griffin S, Challinor L, Rowlands DJ, Harris M A link between translation of the hepatitis C virus polyprotein and polymerase function; possible consequences for hyperphosphorylation of NS5A J GEN VIROL 87 93-102, 2006
DOI:10.1099/vir.0.81180.0

Griffin S, Clarke D, McCormick C, Rowlands D, Harris M Signal peptide cleavage and internal targeting signals direct the hepatitis C virus p7 protein to distinct intracellular membranes. J Virol 79 15525-15536, 2005
DOI:10.1128/JVI.79.24.15525-15536.2005
View abstract

Mann J, Patrick CN, Cragg MS, Honeychurch J, Mann DA, Harris M Functional analysis of HIV type 1 Nef reveals a role for PAK2 as a regulator of cell phenotype and function in the murine dendritic cell line, DC2.4 J IMMUNOL 175 6560-6569, 2005

Dennis CA, Baron A, Grossmann JG, Mazaleyrat S, Harris M, Jaeger J Co-translational myristoylation alters the quaternary structure of HIV-1 Nef in solution PROTEINS 60 658-669, 2005
DOI:10.1002/prot.20544

Macdonald A, Chan JKY, Harris MPG Perturbation of epidermal growth factor receptor complex formation and Ras signalling in cells harbouring the hepatitis C virus subgenomic replicon Journal of General Virology 86 1027-1033, 2005
DOI:10.1099/vir.0.80724-0
View abstract

Street AA, Macdonald A, McCormick CJ, Harris MPG Hepatitis C virus NS5A-mediated activation of phosphoinositide 3-kinase results in stabilization of cellularß-catenin and stimulation of ß-catenin-responsive transcription Journal of Virology 79 5006-5016, 2005
DOI:10.1128/JVI.79.8.5006-5016.2005
View abstract

Macdonald A, Mazaleyrat SL, McCormick CJ, Street AA, Burgoyne NJ, Jackson RM, Cazeaux V, Shelton HA, Saksela K, Harris MPG Further studies on hepatitis C virus NS5A–SH3 domain interactions: identification of residues critical for binding and implications for viral RNA replication and modulation of cell signalling Journal of General Virology 86 1035-1044, 2005
DOI:10.1099/vir.0.80734-0
View abstract

Macdonald A, Harris MPG Hepatitis C virus NS5A: tales of a promiscuous protein Journal of General Virology 85 2485-2502, 2004
DOI:10.1099/vir.0.80204-0
View abstract

Macdonald A, Crowder KJ, Street AA, McCormick CJ, Harris MPG The hepatitis C virus NS5A protein binds to members of the Src family of tyrosine kinases and regulates kinase activity Journal of General Virology 85 721-729, 2004
DOI:10.1099/vir.0.19691-0

Griffin SDC, Harvey R, Clarke DS, Barclay WS, Harris MPG, Rowlands DJ A conserved basic loop in hepatitis C virus p7 protein is required for amantadine-sensitive ion channel activity in mammalian cells but is dispensable for localization to mitochondria. Journal of General Virology 85 451-461, 2004
DOI:10.1099/vir.0.19634-0

McCormick CJ, Challinor LJ, Macdonald A, Rowlands DJ, Harris MPG Introduction of replication-competent hepatitis C virus transcripts using a tetracycline-regulable baculovirus delivery system Journal of General Virology 85 429-439, 2004
DOI:10.1099/vir.0.19676-0
View abstract

Street AA, Macdonald A, Crowder KJ, Harris MPG The Hepatitis C Virus NS5A Protein Activates a Phosphoinositide 3-Kinase-dependent Survival Signaling Cascade Journal of Biological Chemistry 279 12232-12241, 2004
DOI:10.1074/jbc.M312245200

Bentham M, Mazaleyrat S, Harris M The di-leucine motif in the cytoplasmic tail of CD4 is not required for binding to human immunodeficiency virus type 1 Nef, but is critical for CD4 down-modulation J GEN VIROL 84 2705-2713, 2003
DOI:10.1099/vir.0.19274-0

Macdonald A, Crowder KJ, Street AA, McCormick CJ, Saksela K, Harris M The hepatitis C virus non-structural NS5A protein inhibits activating protein-1 function by perturbing Ras-ERK pathway signaling Journal of Biological Chemistry 278 17775-17784, 2003
DOI:10.1074/jbc.M210900200
View abstract

Macdonald A, Crowder KJ, Street AA, McCormick CJ, Saksela K, Harris MPG The Hepatitis C Virus Non-structural NS5A Protein Inhibits Activating Protein-1 Function by Perturbing Ras-ERK Pathway Signaling Journal of Biological Chemistry 278 17775-17784, 2003
DOI:10.1074/jbc.M210900200

Olivetta E, Percario Z, Fiorucci G, Mattia G, Schiavoni A, Dennis C, Jager J, Harris M, Romeo G, Affabris E, Federico M HIV-1 Nef induces the release of inflammatory factors from human monocyte/macrophages: Involvement of nef endocytotic signals and NF-kappa B activation J IMMUNOL 170 1716-1727, 2003

Griffin SDC, Beales LP, Clarke DS, Worsfold O, Evans SD, Jaeger J, Harris MPG, Rowlands DJ The p7 protein of hepatitis C virus forms an ion channel that is blocked by the antiviral drug, Amantadine FEBS LETT 535 34-38, 2003
DOI:10.1016/S0014-5793(02)03851-6

McCormick CJ, Rowlands DJ, Harris M Efficient delivery and regulable expression of hepatitis C virus full-length and minigenome constructs in hepatocyte-derived cell lines using baculovirus vectors. J Gen Virol 83 383-394, 2002
DOI:10.1099/0022-1317-83-2-383
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Gao R, McCormick CJ, Arthur MJP, Ruddell R, Oakley F, Smart DE, Murphy FR, Harris MPG, Mann DA High efficiency gene transfer into cultured primary rat and human hepatic stellate cells using baculovirus vectors Liver 22 15-22, 2002
DOI:10.1046/j.0106-9543.2001.01555.x

Aoubala M, Holt J, Clegg RA, Rowlands DJ, Harris M The inhibition of cAMP-dependent protein kinase by full-length hepatitis C virus NS3/4A complex is due to ATP hydrolysis. J Gen Virol 82 1637-1646, 2001
DOI:10.1099/0022-1317-82-7-1637
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Mann DA, Gao RP, Harris M, McCormick B, Arthur MJP Efficient gene transfer into rat hepatic stellate cells using recombinant baculovirus vectors J HEPATOL 34 92-92, 2001

Renkema GH, Manninen A, Mann DA, Harris M, Saksela K Identification of the Nef-associated kinase as p21-activated kinase 2 CURR BIOL 9 1407-1410, 1999

Harris M HIV: a new role for Nef in the spread of HIV. Curr Biol 9 R459-R461, 1999
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Biggs TE, Cooke SJ, Barton CH, Harris MPG, Saksela K, Mann DA Induction of activator protein 1 (AP-1) in macrophages by human immunodeficiency virus type-1 NEF is a cell-type-specific response that requires both Hck and MAPK signaling events Journal of Molecular Biology 290 21-35, 1999

Argyle DJ, Harris M, Lawrence C, McBride K, Barron R, McGillivray C, Onions DE Expression of feline recombinant interferon-gamma in baculovirus and demonstration of biological activity. Vet Immunol Immunopathol 64 97-105, 1998
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Dutartre H, Harris MPG, Olive D, Collette Y The Human Immunodeficiency Virus type 1 Nef protein binds the Src-related tyrosine kinase Lck SH2 domain through a novel phosphotyrosine independent mechanism. Virology 247 200-211, 1998

Harris MPG Use of GST-fusion and related constructs for the identification of interacting proteins. In Methods in Molecular Biology: Protein Targeting Protocols , 1998

Welker R, Harris MPG, Cardel B, Krausslich HG Virion incorporation of Human Immunodeficiency Virus Type 1 Nef is mediated by bipartite membrane targeting signal: analysis of its role in enhancement of viral infectivity. Journal of Virology 72 8833-8840, 1998

Cooke SJ, Coates K, Barton CH, Biggs TE, Barrett SJ, Cochrane A, Oliver K, McKeating JA, Harris MPG, Mann DA Regulated expression vectors demonstrate cell-type-specific sensitivity to human immunodeficiency virus type 1 Nef-induced cytostasis Journal of General Virology 78 381-392, 1997
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Cooke SJ, Coates K, Barton CH, Biggs TE, Barrett SJ, Cochrane A, Oliver K, McKeating JA, Harris MPG, Mann DA Regulated expression vectors demonstrate cell-type specific sensitivity to HIV-1 Nef-induced cytostasis. Journal of General Virology 78 381-392, 1997

Coates K, Cooke SJ, Mann DA, Harris MPG Protein kinase C mediated phosphorylation of HIV-1 Nef in human cell lines Journal of Biological Chemistry 272 12289-12294, 1997

Coates K, Boulton V, Cooke S, Mann D, Harris M Analysis of the interactions between Nef and cellular proteins. Res Virol 148 68-70, 1997

Collette Y, Dutartre H, Benziane A, Romos-Morales F, Benarous R, Harris MPG, Olive D Physical and functional interaction of Nef with Lck: HIV-1 Nef induced T-cell signalling defects. Journal of Biological Chemistry 271 6333-6341, 1996

Harris MPG From negative factor to a critical role in viral pathogenesis: The changing fortunes of Nef. Journal of General Virology 77 2379-2392, 1996

Harris M The role of myristoylation in the interactions between human immunodeficiency virus type I Nef and cellular proteins. Biochem Soc Trans 23 557-561, 1995

Coates K, Harris M The human immunodeficiency virus type 1 Nef protein functions as a protein kinase C substrate in vitro. J Gen Virol 76 ( Pt 4) 837-844, 1995
DOI:10.1099/0022-1317-76-4-837
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P M, Harris G, Neil JC Myristoylation-dependent Binding of HIV-1 Nef to CD4 Journal of Molecular Biology 241 136-142, 1994
DOI:10.1006/jmbi.1994.1483
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Harris M, Coates K Identification of cellular proteins that bind to the human immunodeficiency virus type 1 nef gene product in vitro: a role for myristylation. J Gen Virol 74 ( Pt 8) 1581-1589, 1993
DOI:10.1099/0022-1317-74-8-1581
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Harris M, Talbot S, Patsilinacos P, Neil JC The HIV-1 nef gene product. Biochem Soc Trans 20 517-520, 1992

Harris M, Hislop S, Patsilinacos P, Neil JC In vivo derived HIV-1 nef gene products are heterogeneous and lack detectable nucleotide binding activity. AIDS Res Hum Retroviruses 8 537-543, 1992
DOI:10.1089/aid.1992.8.537
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Merryweather AT, Weyer U, Harris MPG, Hirst M, Booth T, Possee RD Construction of genetically engineered baculovirus insecticides containing the Bacillus thuringiensis subsp. kurstaki HD-73 delta endotoxin Journal of General Virology 71 1535-1544, 1990
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Harris MPG, Hay RT DNA sequences required for the initiation of adenovirus type 4 DNA replication in vitro Journal of Molecular Biology 201 57-67, 1988
DOI:10.1016/0022-2836(88)90438-X
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HAY RT, BARRETT P, CLARK L, HARRIS M THE ROLE OF SEQUENCE-SPECIFIC DNA-BINDING PROTEINS IN ADENOVIRUS DNA-REPLICATION J CELL SCI 51-65, 1987