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

285 results found

Fairhurst D, Rowell RL, Monahan IM, Key S, Stieh D, McNeil-Watson F, Morfesis A, Mitchnick M, Shattock RAet al., 2007, Microbicides for HIV/AIDS. 2. Electrophoretic fingerprinting of CD4+ T-cell model systems., Langmuir, Vol: 23, Pages: 2680-2687, ISSN: 0743-7463

New measurements of the dependence of the surface charge on the pH and electrolyte concentration for three living human white blood cell lines that are the principal targets of the HIV-1 virus are reported. Comparison of the electrophoretic fingerprint (EF) pattern, especially the line of zero mobility, with that of reference colloids establishes the separate individual identities and shows that all three exhibit a zwitterionic surface. With the EF results as a guide, preliminary biological infectivity measurements showed that small polyvalent cations modulate the negative charge on the T-cell surface in a way that strongly affects the infection kinetics. H9 cells were exposed to an infectious virus (X4), and the data showed that HIV interaction with target cells is enhanced by physiological fluids. The nondestructive methodology described is generally applicable to characterization of the surface charge and determination of the colloidal stability of any aqueous charged colloidal system without reference to any model of the double layer.

Journal article

Hu Q, Younson J, Griffin GE, Kelly C, Shattock RJet al., 2006, Pertussis toxin and its binding unit inhibit HIV-1 infection of human cervical tissue and macrophages involving a CD14 pathway, JOURNAL OF INFECTIOUS DISEASES, Vol: 194, Pages: 1547-1556, ISSN: 0022-1899

Journal article

Ramjee G, Shattock R, Delany S, McGowan I, Morar N, Gottemoeller Met al., 2006, Microbicides 2006 conference., AIDS Res Ther, Vol: 3

Current HIV/AIDS statistics show that women account for almost 60% of HIV infections in Sub-Saharan Africa. HIV prevention tools such as male and female condoms, abstinence and monogamy are not always feasible options for women due to various socio-economic and cultural factors. Microbicides are products designed to be inserted in the vagina or rectum prior to sex to prevent HIV acquisition. The biannual Microbicides conference took place in Cape Town, South Africa from 23-26 April 2006. The conference was held for the first time on the African continent, the region worst affected by the HIV/AIDS pandemic. The conference brought together a record number of 1,300 scientists, researchers, policy makers, healthcare workers, communities and advocates. The conference provided an opportunity for an update on microbicide research and development as well as discussions around key issues such as ethics, acceptability, access and community involvement. This report discusses the current status of microbicide research and development, encompassing basic and clinical science, social and behavioural science, and community mobilisation and advocacy activities.

Journal article

Klasse PJ, Shattock RJ, Moore JP, 2006, Which topical microbicides for blocking HIV-1 transmission will work in the real world?, PLOS MEDICINE, Vol: 3, Pages: 1501-1507, ISSN: 1549-1676

Journal article

Soilleux EJ, Sarno EN, Hernandez MO, Moseley E, Horsley J, Lopes UG, Goddard MJ, Vowler SL, Coleman N, Shattock RJ, Sampaio EPet al., 2006, DC-SIGN association with the Th2 environment of lepromatous leprosy lesions: cause or effect?, 190th Meeting of the Pathological-Society-of-Great-Britain-and-Ireland, Publisher: JOHN WILEY & SONS LTD, Pages: 55-55, ISSN: 0022-3417

Conference paper

Siddiqui AA, Shattock RJ, Harrison TS, 2006, Role of capsule and interleukin-6 in long-term immune control of Cryptococcus neoformans infection by specifically activated human peripheral blood mononuclear cells, INFECTION AND IMMUNITY, Vol: 74, Pages: 5302-5310, ISSN: 0019-9567

Journal article

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

Journal article

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

Journal article

Arias MA, Pantoja AE, Jaramillo G, Paris SC, Shattock RJ, Garcia LF, Griffin GEet al., 2006, Chemokine receptor expression and modulation by Mycobacterium tuberculosis antigens on mononuclear cells from human lymphoid tissues, IMMUNOLOGY, Vol: 118, Pages: 171-184, ISSN: 0019-2805

Journal article

Soilleux EJ, Sarno EN, Hernandez MO, Moseley E, Horsley J, Lopes UG, Goddard MJ, Vowler SL, Coleman N, Shattock RJ, Sampaio EPet al., 2006, DC-SIGN association with the Th2 environment of lepromatous lesions: cause or effect?, J Pathol, Vol: 209, Pages: 182-189, ISSN: 0022-3417

The clinical spectrum of leprosy is related to patients' immune responses. Non-responsiveness towards Mycobacterium leprae (ML) seems to correlate with a Th2 cytokine profile. The reason for such a polarized immune response remains unclear. The C-type lectin, DC-SIGN, expressed by subsets of dendritic cells (DCs) and macrophages, has previously been associated with Th2 responses. Here we show abundant DC-SIGN expression in lepromatous but not borderline tuberculoid leprosy, in both HIV-positive and HIV-negative patients. Moreover, we demonstrate that DC-SIGN can act as an entry receptor for ML, as it does for M. tuberculosis, through the cell wall component lipoarabinomannan. DC-SIGN is expressed on virtually all ML-containing cells, providing further evidence for its role as a receptor. DC-SIGN may therefore be induced on macrophages in lepromatous leprosy and may then contribute to mycobacterial entry into these cells.

Journal article

Harman SJ, Fletcher P, Shattock RJ, Doncel Get al., 2006, Preclinical evaluation of lime juice as a potential microbicide, Microbicides 2006

Conference paper

Lu H, Zhao Q, Wallace G, Liu S, He Y, Shattock R, Neurath AR, Jiang BSet al., 2006, Cellulose acetate 1,2-benzenedicarboxylate inhibits infection by cell-free and cell-associated primary HIV-1 isolates., AIDS Res Hum Retroviruses, Vol: 22, Pages: 411-418, ISSN: 0889-2229

Cellulose acetate 1,2-benzenedicarboxylate (CAP), a pharmaceutical excipient used for enteric film coating of capsules and tablets, was previously shown to have potent inhibitory activity against infection by human immunodeficiency virus type 1 (HIV-1) T cell line-adapted (TCLA) strains. In the present study, we determined the inhibitory activity of CAP against infection by cell-free and cell-associated primary HIV-1 isolates with distinct genotypes and biotypes in cervical explants, peripheral blood mononuclear cells (PBMCs), monocytederived macrophages (MDMs), and CEMx174 5.25M7 cells. CAP blocked infection by cell-free and cell-associated HIV-1 in cervical explants. It inhibited infection by cell-free primary HIV-1 isolates (clades A to G and group O) in PBMCs, MDMs, and CEMx174 5.25M7 cells and blocked transmissions of the cell-associated primary HIV-1 isolates from dendritic cells (DCs) to PBMCs, from MDMs to PBMCs, and from PBMCs to CEMx174 5.25M7 cells. The inhibitory activity of CAP on infection by the cell-free and cell-associated primary HIV-1 isolates is independent of viral subtypes and coreceptor usage. These data suggest that CAP is a good microbicide candidate that can be further developed for preventing sexual transmission of HIV-1.

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., BJU Int, Vol: 97, Pages: 1043-1046, ISSN: 1464-4096

OBJECTIVE: To investigate whether a range of cytokines were detectable in the seminal plasma and urine of men with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and nonspecific urethritis (NSU), and whether cytokine levels correlated with symptom severity in CP/CPPS. PATIENTS AND METHODS: In all, 87 men participated, 33 with CP/CPPS, 31 with NSU, and 23 controls. Interleukin (IL)-1beta, IL-2, IL-6, IL-8 and IL-10 were measured in seminal plasma and first pass urine, and the results were correlated with scores for pain, urinary symptoms and quality-of-life impact using a validated symptom index, the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI). RESULTS: Seminal plasma levels of IL-8 were higher in men with CP/CPPS and NSU than in controls (P < 0.001), and the levels correlated with NIH-CPSI symptom scores in men with CP/CPPS. There were no significant differences in urinary IL-8 levels in the three groups, and no significant differences in levels of the other cytokines in either semen or urine. CONCLUSION: Semen IL-8 levels correlate with subjective symptoms in men with CP/CPPS. IL-8 might contribute to the pathophysiology of CP/CPPS and NSU, and elevated levels might be a useful marker of the condition.

Journal article

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

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

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, Vol: 50, Pages: 713-723, ISSN: 0066-4804

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

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

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

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

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