Publications
382 results found
Madan RP, Mesquita PMM, Cheshenko N, et al., 2007, Molecular umbrellas: a novel class of candidate topical microbicides to prevent human immunodeficiency virus and herpes simplex virus infections, JOURNAL OF VIROLOGY, Vol: 81, Pages: 7636-7646, ISSN: 0022-538X
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- Citations: 32
Grivel J-C, Elliott J, Lisco A, et al., 2007, HIV-1 pathogenesis differs in rectosigmoid and tonsillar tissues infected <i>ex vivo</i> with CCR5-and CXCR4-tropic HIV-1, AIDS, Vol: 21, Pages: 1263-1272, ISSN: 0269-9370
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- Citations: 57
McFadden K, Cocklin S, Gopi H, et al., 2007, A recombinant allosteric lectin antagonist of HIV-1 envelope gp120 interactions., Proteins, Vol: 67, Pages: 617-629
The first, critical stage of HIV-1 infection is fusion of viral and host cellular membranes initiated by a viral envelope glycoprotein gp120. We evaluated the potential to form a chimeric protein entry inhibitor that combines the action of two gp120-targeting molecules, an allosteric peptide inhibitor 12p1 and a higher affinity carbohydrate-binding protein cyanovirin (CVN). In initial mixing experiments, we demonstrated that the inhibitors do not interfere with each other and instead show functional synergy in inhibiting viral cell infection. Based on this, we created a chimera, termed L5, with 12p1 fused to the C-terminal domain of CVN through a linker of five penta-peptide repeats. L5 revealed the same broad specificity as CVN for gp120 from a variety of clades and tropisms. By comparison to CVN, the L5 chimera exhibited substantially increased inhibition of gp120 binding to receptor CD4, coreceptor surrogate mAb 17b and gp120 antibody F105. These binding inhibition effects by the chimera reflected both the high affinity of the CVN domain and the allosteric action of the 12p1 domain. The results open up the possibility to form high potency chimeras, as well as noncovalent mixtures, as leads for HIV-1 envelope antagonism that can overcome potency limits and potential virus mutational resistance for either 12p1 or CVN alone.
Arias MA, Pantoja AE, Jaramillo G, et al., 2007, Chemokine/cytokine production by mononuclear cells from human lymphoid tissues and their modulation by <i>Mycobacterium tuberculosis</i> antigens, FEMS IMMUNOLOGY AND MEDICAL MICROBIOLOGY, Vol: 49, Pages: 272-279, ISSN: 0928-8244
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- Citations: 4
Fairhurst D, Rowell RL, Monahan IM, et 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.
Hu Q, Shattock R, 2007, Novel antiviral agents targeting HIV entry and transmission, Virologica Sinica, Vol: 22, Pages: 451-461, ISSN: 1003-5125
Studies of the mechanism of HIV entry and transmission have identified multiple new targets for drug development. A range of inhibitors have demonstrated potent antiretroviral activity by interfering with CD4-gp120 interaction, coreceptor binding or viral-cell fusion in preclinical and clinical studies. One of these agents, fusion inhibitor enfuvirtide, is already in clinical use. Here we review the progress in the development of specific entry inhibitors as novel therapeutics. The potential of entry inhibitors as topical microbicides to block HIV transmission is also discussed.
Hu Q, Younson J, Griffin GE, et 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
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- Citations: 9
Ahuja SK, Aiuti F, Berkhout B, et al., 2006, A plea for justice for jailed medical workers., Science, Vol: 314, Pages: 924-925
Ramjee G, Shattock R, Delany S, et 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.
Siddiqui AA, Shattock RJ, Harrison TS, 2006, Role of capsule and interleukin-6 in long-term immune control of <i>Cryptococcus neoformans</i> infection by specifically activated human peripheral blood mononuclear cells, INFECTION AND IMMUNITY, Vol: 74, Pages: 5302-5310, ISSN: 0019-9567
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- Citations: 23
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
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- Citations: 57
Soilleux EJ, Sarno EN, Hernandez MO, et 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
Fletcher PS, Wallace GS, Mesquita PMM, et al., 2006, Candidate polyanion microbicides inhibit HIV-1 infection and dissemination pathways in human cervical explants, RETROVIROLOGY, Vol: 3, ISSN: 1742-4690
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- Citations: 70
Fletcher PS, Elliott J, Grivel J-C, et al., 2006, <i>Ex vivo</i> culture of human colorectal tissue for the evaluation of candidate microbicides, AIDS, Vol: 20, Pages: 1237-1245, ISSN: 0269-9370
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- Citations: 120
Soilleux EJ, Sarno EN, Hernandez MO, et al., 2006, DC-SIGN association with the Th2 environment of lepromatous lesions: cause or effect?, JOURNAL OF PATHOLOGY, Vol: 209, Pages: 182-189, ISSN: 0022-3417
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- Citations: 24
Arias MA, Pantoja AE, Jaramillo G, et al., 2006, Chemokine receptor expression and modulation by <i>Mycobacterium tuberculosis</i> antigens on mononuclear cells from human lymphoid tissues, IMMUNOLOGY, Vol: 118, Pages: 171-184, ISSN: 0019-2805
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- Citations: 13
Margolis L, Shattock R, 2006, Erratum: Selective transmission of CCR5-utilizing HIV-1: The 'gatekeeper' problem resolved? (Nature Reviews Microbiology (2006) vol. 4 (312-317) 10.1038/nrmicro1387), Nature Reviews Microbiology, Vol: 4, ISSN: 1740-1526
Harman SJ, Fletcher P, Shattock RJ, et al., 2006, Preclinical evaluation of lime juice as a potential microbicide, Microbicides 2006
Lu H, Zhao Q, Wallace G, et 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.
Khadra A, Fletcher P, Luzzi G, et 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.
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.
Beer BE, Doncel GF, Krebs FC, et 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
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- Citations: 49
Sexton A, Drake PM, Mahmood N, et al., 2006, Transgenic plant production of Cyanovirin-N, an HIV microbicide, FASEB JOURNAL, Vol: 20, Pages: 356-358, ISSN: 0892-6638
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- Citations: 65
Beer BE, Doncel GF, Krebs FC, et 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
Khadra A, Fletcher P, Luzzi G, et 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
Fletcher PS, Elliott J, Grivel JC, et al., 2006, Ex vivo culture of human colorectal tissue for the evaluation of candidate microbicides, Vol: 20, Pages: 1237-1245, ISSN: 0269-9370
Fletcher PS, Wallace GS, Mesquita PM, et al., 2006, Candidate polyanion microbicides inhibit HIV-1 infection and dissemination pathways in human cervical explants, Vol: 3, ISSN: 1742-4690
Sexton A, Drake PM, Mahmood N, et al., 2005, Transgenic plant production of Cyanovirin-N, an HIV microbicide, FASEB JOURNAL, Vol: 19, Pages: 356-+, ISSN: 0892-6638
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- Citations: 1
Veazey RS, Klasse PJ, Schader SM, et 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
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- Citations: 256
Rowell RL, Fairhurst D, Key S, et 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.
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