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.
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
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
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
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
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
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
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
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
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.
Fletcher P, Kiselyeva Y, Wallace G, et 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.
Harman SJ, Perumal D, Fletcher P, et al., 2005, TMC120 blocks HIV-1 infection in cellular and human cervical tissue models, International AIDS Society 2005
Hu QX, Napier KB, Trent JO, et 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
Hillier SL, Moench T, Shattock R, et 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.
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
Siddiqui AA, Brouwer AE, Wuthiekanun V, et 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.
Fletcher P, Kiselyeva Y, Wallace G, et 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
Derry DD, Possee RD, Griffin GE, et 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
Hu QX, Frank I, Williams V, et 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
Harman SJ, Watts P, Van Roey J, et al., 2004, TMC120 blocks HIV-1 infection in cellular and human cervical tissue models, Microbicides 2004
Shattock R, Solomon S, 2004, Microbicides--aids to safer sex., Lancet, Vol: 363, Pages: 1002-1003
Tsai CC, Emau P, Jiang YH, et 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
Hu Q, Frank I, Williams V, et al., 2004, Blockade of attachment and fusion receptors inhibits HIV-1 infection of human cervical tissue, Vol: 199, Pages: 1065-1075, ISSN: 0022-1007
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
Shattock RJ, Moore JP, 2003, Inhibiting sexual transmission of HIV-1 infection, NATURE REVIEWS MICROBIOLOGY, Vol: 1, Pages: 25-34, ISSN: 1740-1526
Oakeshott P, Hay P, Hay S, et al., 2003, Inflammatory markers in the vagina in early pregnancy., Int J STD AIDS, Vol: 14, Pages: 289-290, ISSN: 0956-4624
Veazey RS, Shattock RJ, Pope M, et 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
Miller CJ, Shattock RJ, 2003, Target cells in vaginal HIV transmission, MICROBES AND INFECTION, Vol: 5, Pages: 59-67, ISSN: 1286-4579
Shattock RJ, Doms RW, 2002, AIDS models: Microbicides could learn from vaccines, NATURE MEDICINE, Vol: 8, Pages: 425-425, ISSN: 1078-8956
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