Imperial College London

ProfessorRobinShattock

Faculty of MedicineDepartment of Infectious Disease

Chair in Mucosal Infection and Immunity
 
 
 
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Contact

 

+44 (0)20 7594 5206r.shattock

 
 
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Location

 

453Wright Fleming WingSt Mary's Campus

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Summary

 

Publications

Publication Type
Year
to

272 results found

Margolis L, Shattock R, 2006, Selective transmission of CCR5-utilizing HIV-1: the 'gatekeeper' problem resolved?, Nat Rev Microbiol, Vol: 4, Pages: 312-317, ISSN: 1740-1526

Understanding the mechanisms of HIV-1 transmission is crucial for the development of effective preventive microbicides and vaccine strategies, and remains one of the main goals of HIV research. Over the past decade, many studies have focused on trying to identify the 'gatekeeping' mechanism that restricts the transmission of CXCR4-utilizing HIV-1 more efficiently than CCR5-utilizing HIV-1. However, to date, no study has explained the almost perfect negative selection of the former in vivo. Here, we propose that there is no single gatekeeper and that, instead, the selective transmission of R5 HIV-1 depends on the superimposition of multiple imperfect gatekeepers.

Journal article

Sexton A, Drake PM, Mahmood N, Harman SJ, Shattock RJ, Ma JK-Cet al., 2006, Transgenic plant production of Cyanovirin-N, an HIV microbicide, FASEB JOURNAL, Vol: 20, Pages: 356-358, ISSN: 0892-6638

Journal article

Beer BE, Doncel GF, Krebs FC, Shattock RJ, Fletcher PS, Buckheit RW, Watson K, Dezzutti CS, Cummins JE, Bromley E, Richardson-Harman N, Pallansch LA, Lackman-Smith C, Osterling C, Mankowski M, Miller SR, Catalone BJ, Welsh PA, Howett MK, Wigdahl B, Turpin JA, Reichelderfer Pet al., 2006, In vitro preclinical testing of nonoxynol-9 as potential anti-human immunodeficiency virus microbicide: a retrospective analysis of results from five laboratories, ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Vol: 50, Pages: 713-723, ISSN: 0066-4804

Journal article

Fletcher PS, Wallace GS, Mesquita PM, Shattock RJet al., 2006, Candidate polyanion microbicides inhibit HIV-1 infection and dissemination pathways in human cervical explants, Vol: 3, ISSN: 1742-4690

Journal article

Fletcher PS, Elliott J, Grivel JC, Margolis L, Anton P, McGowan I, Shattock RJet al., 2006, Ex vivo culture of human colorectal tissue for the evaluation of candidate microbicides, Vol: 20, Pages: 1237-1245, ISSN: 0269-9370

Journal article

Khadra A, Fletcher P, Luzzi G, Shattock R, Hay Pet al., 2006, Interleukin-8 levels in seminal plasma in chronic prostatitis/chronic pelvic pain syndrome and nonspecific urethritis, Vol: 97, Pages: 1043-1046, ISSN: 1464-4096

Journal article

Beer BE, Doncel GF, Krebs FC, Shattock RJ, Fletcher PS, Buckheit RW, Watson K, Dezzutti CS, Cummins JE, Bromley E, Richardson-Harman N, Pallansch LA, Lackman-Smith C, Osterling C, Mankowski M, Miller SR, Catalone BJ, Welsh PA, Howett MK, Wigdahl B, Turpin JA, Reichelderfer Pet al., 2006, In vitro preclinical testing of nonoxynol-9 as potential anti-human immunodeficiency virus microbicide: a retrospective analysis of results from five laboratories, Vol: 50, Pages: 713-723, ISSN: 0066-4804

Journal article

Sexton A, Drake PM, Mahmood N, Harman SJ, Shattock RJ, Ma JKCet al., 2005, Transgenic plant production of Cyanovirin-N, an HIV microbicide, FASEB JOURNAL, Vol: 19, Pages: 356-+, ISSN: 0892-6638

Journal article

Veazey RS, Klasse PJ, Schader SM, Hu QX, Ketas TJ, Lu M, Marx PA, Dufour J, Colonno RJ, Shattock RJ, Springer MS, Moore JPet al., 2005, Protection of macaques from vaginal SHIV challenge by vaginally delivered inhibitors of virus-cell fusion, NATURE, Vol: 438, Pages: 99-102, ISSN: 0028-0836

Journal article

Rowell RL, Fairhurst D, Key S, Morfesis A, Monahan IM, Mitchnick M, Shattock RAet al., 2005, Microbicides for HIV/AIDS. 1. Electrophoretic fingerprinting the H9 cell model system., Langmuir, Vol: 21, Pages: 10165-10171, ISSN: 0743-7463

An electrophoretic fingerprint of a CD4+ T-cell (H9) has been produced for the first time. Samples were taken from three separate cultures prepared at different times to obtain a general characterization of the cells. The availability of commercial instrumentation equipped with an auto-titrator has made possible the application of both the 2-dimensional and 3-dimensional representation of electrophoretic fingerprinting. The 2-dimensional treatment has been used to assess the reliability of the data and has detected hysteresis as a possible second-order effect. The 3-dimensional representation has been used to explore the data needed for a reliable overall pattern that characterizes the conditions of pH and conductivity required for an effective microbicide. The dome negative maximum in the electrophoretic fingerprint at high pH, along with the line of zero mobility (LZM) and a dome positive maximum at low pH, are interpreted as evidence for surface carboxyl groups prominent in the alkaline regime and surface amino groups prominent in the acid regime, suggesting that the H9 cell surface is zwitterionic. This has important implications as to the choice and design of microbicide actives.

Journal article

Fletcher P, Kiselyeva Y, Wallace G, Romano J, Griffin G, Margolis L, Shattock Ret al., 2005, The nonnucleoside reverse transcriptase inhibitor UC-781 inhibits human immunodeficiency virus type 1 infection of human cervical tissue and dissemination by migratory cells., J Virol, Vol: 79, Pages: 11179-11186, ISSN: 0022-538X

Heterosexual transmission of human immunodeficiency virus remains the major route of transmission worldwide; thus, there is an urgent need for additional prevention strategies, particularly those that could be controlled by women. Using cellular and tissue explant models, we have evaluated the potential activity of thiocarboxanilide nonnucleoside analogue reverse transcriptase inhibitor UC-781 as a vaginal microbicide. We were able to demonstrate a potent dose-dependent effect against R5 and X4 infections of T cells. In human cervical explant cultures, UC-781 was not only able to inhibit direct infection of mucosal tissue but was able to prevent dissemination of virus by migratory cells. UC-781 formulated into a carbopol gel (0.1%) retained significant activity against both direct tissue infection and transinfection mediated by migratory cells. Furthermore, UC-781 demonstrated prolonged inhibitory effects able to prevent both localized and disseminated infections up to 6 days post compound treatment. Additional studies were carried out to determine the concentration of compound that might be required to block a primary infection within draining lymph nodes. While a greater dose of compound was required to inhibit both X4 and R5 infections of lymphoid versus cervical explants, this was equivalent to a 1:3,000 dilution of the 0.1% formulation. Furthermore, a 2-h exposure to the compound prevented infection of lymphoid tissue when challenged up to 2 days later. The prolonged protection observed following pretreatment of both genital and lymphoid tissues with UC-781 suggests that this class of inhibitors may have unique advantages over other classes of potential microbicide candidates.

Journal article

Harman SJ, Perumal D, Fletcher P, Van Roey J, Gwozdz G, Fairhurst D, Mitchnik M, Shattock RJet al., 2005, TMC120 blocks HIV-1 infection in cellular and human cervical tissue models, International AIDS Society 2005

Conference paper

Hu QX, Napier KB, Trent JO, Wang ZX, Taylor S, Griffin GE, Peiper SC, Shattock RJet al., 2005, Restricted variable residues in the C-terminal segment of HIV-1V3 loop regulate the molecular anatomy of CCR5 utilization, JOURNAL OF MOLECULAR BIOLOGY, Vol: 350, Pages: 699-712, ISSN: 0022-2836

Journal article

Hillier SL, Moench T, Shattock R, Black R, Reichelderfer P, Veronese Fet al., 2005, In vitro and in vivo: the story of nonoxynol 9., J Acquir Immune Defic Syndr, Vol: 39, Pages: 1-8, ISSN: 1525-4135

There is an urgent need to expand the range of interventions to prevent HIV transmission and acquisition, especially those that can be controlled by women. Microbicides, defined as antimicrobial products that can be applied topically for the prevention of HIV and other sexually transmitted infections, may offer one of the most promising preventive interventions, because they could be inexpensive, readily available, and widely acceptable. The first microbial product to be clinically evaluated contained Nonoxynol-9 (nonylpenoxypolyethoxyethanol [N-9]), a nonionic surfactant, as the active agent. This article presents a review of the in vitro, ex vivo, and animal model data on the safety of N-9 and a critical analysis of their predictive power based on the results of multiple safety and efficacy trials.

Journal article

Hillier SL, Moench T, Shattock R, Black R, Reichelderfer P, Veronese Fet al., 2005, In Vitro and In Vivo, JAIDS Journal of Acquired Immune Deficiency Syndromes, Vol: 39, Pages: 1-8, ISSN: 1525-4135

Journal article

Meireles-De-Souza LR, Shattock RJ, 2005, Therapeutic role of CD8(+) T cells in HIV-1 infection: targets and suppressors of viral replication, EXPERT OPINION ON BIOLOGICAL THERAPY, Vol: 5, Pages: 321-332, ISSN: 1471-2598

Journal article

Siddiqui AA, Brouwer AE, Wuthiekanun V, Jaffar S, Shattock R, Irving D, Sheldon J, Chierakul W, Peacock S, Day N, White NJ, Harrison TSet al., 2005, IFN-gamma at the site of infection determines rate of clearance of infection in cryptococcal meningitis., J Immunol, Vol: 174, Pages: 1746-1750, ISSN: 0022-1767

In animal models, immunity to cryptococcal infection, as in many chronic fungal and bacterial infections, is associated with a granulomatous inflammatory response, intact cell-mediated immunity, and a Th1 pattern of cytokine release. To examine the correlates of human immunity to cryptococcal infection in vivo, we analyzed immune parameters at the site of infection over time and assessed the rate of clearance of infection by serial quantitative cerebrospinal fluid (CSF) fungal cultures in 62 patients in a trial of antifungal therapy for HIV-associated cryptococcal meningitis. CSF IL-6, IFN-gamma, TNF-alpha, and IL-8 were significantly higher in survivors compared with nonsurvivors. There were negative correlations between log TNF-alpha, IFN-gamma, and IL-6 levels and baseline cryptococcal CFU. Log IFN-gamma, G-CSF, TNF-alpha, and IL-6 were correlated positively with the rate of fall in log CFU/ml CSF/day. In a linear regression model including antifungal treatment group, baseline CFU, and these cytokines, only treatment group and log IFN-gamma remained independently associated with rate of clearance of infection. The results provide direct in vivo evidence for the importance of quantitative differences in IFN-gamma secretion in human immune control of granulomatous infections, and increase the rationale for adjunctive IFN-gamma in the treatment of refractory HIV-associated cryptococcosis.

Journal article

Fletcher P, Kiselyeva Y, Wallace G, Romano J, Griffin G, Margolis L, Shattock Ret al., 2005, The nonnucleoside reverse transcriptase inhibitor UC-781 inhibits human immunodeficiency virus type 1 infection of human cervical tissue and dissemination by migratory cells, Vol: 79, Pages: 11179-11186, ISSN: 0022-538X

Journal article

Derry DD, Possee RD, Griffin GE, Shattock RJet al., 2004, Discovery of proteins with role in defence against infection, Winter Meeting of the British-Thoracic-Society, Publisher: B M J PUBLISHING GROUP, Pages: 17-17, ISSN: 0040-6376

Conference paper

Hu QX, Frank I, Williams V, Santos JJ, Watts P, Griffin GE, Moore JR, Pope M, Shattock RJet al., 2004, Blockade of attachment and fusion receptors inhibits HIV-1 infection of human cervical tissue, JOURNAL OF EXPERIMENTAL MEDICINE, Vol: 199, Pages: 1065-1075, ISSN: 0022-1007

Journal article

Harman SJ, Watts P, Van Roey J, Griffin G, Shattock RJet al., 2004, TMC120 blocks HIV-1 infection in cellular and human cervical tissue models, Microbicides 2004

Conference paper

Shattock R, Solomon S, 2004, Microbicides--aids to safer sex., Lancet, Vol: 363, Pages: 1002-1003

Journal article

Tsai CC, Emau P, Jiang YH, Agy MB, Shattock RJ, Schmidt A, Morton WR, Gustafson KR, Boyd MRet al., 2004, Cyanovirin-N inhibits AIDS virus infections in vaginal transmission models, AIDS RESEARCH AND HUMAN RETROVIRUSES, Vol: 20, Pages: 11-18, ISSN: 0889-2229

Journal article

Hu Q, Frank I, Williams V, Santos JJ, Watts P, Griffin GE, Moore JP, Pope M, Shattock RJet al., 2004, Blockade of attachment and fusion receptors inhibits HIV-1 infection of human cervical tissue, Vol: 199, Pages: 1065-1075, ISSN: 0022-1007

Journal article

Moore JP, Shattock RJ, 2003, Preventing HIV-1 sexual transmission - not sexy enough science, or no benefit to the bottom line?, JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, Vol: 52, Pages: 890-892, ISSN: 0305-7453

Journal article

Shattock RJ, Moore JP, 2003, Inhibiting sexual transmission of HIV-1 infection, NATURE REVIEWS MICROBIOLOGY, Vol: 1, Pages: 25-34, ISSN: 1740-1526

Journal article

Oakeshott P, Hay P, Hay S, Adefowora A, Shattock Ret al., 2003, Inflammatory markers in the vagina in early pregnancy., Int J STD AIDS, Vol: 14, Pages: 289-290, ISSN: 0956-4624

Journal article

Veazey RS, Shattock RJ, Pope M, Kirijan JC, Jones J, Hu QX, Ketas T, Marx PA, Klasse PJ, Burton DR, Moore JPet al., 2003, Prevention of virus transmission to macaque monkeys by a vaginally applied monoclonal antibody to HIV-1 gp120, NATURE MEDICINE, Vol: 9, Pages: 343-346, ISSN: 1078-8956

Journal article

Miller CJ, Shattock RJ, 2003, Target cells in vaginal HIV transmission, MICROBES AND INFECTION, Vol: 5, Pages: 59-67, ISSN: 1286-4579

Journal article

Shattock RJ, Doms RW, 2002, AIDS models: Microbicides could learn from vaccines, NATURE MEDICINE, Vol: 8, Pages: 425-425, ISSN: 1078-8956

Journal article

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