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Antimicrobial Peptide Resistance and Immunomodulation by HIV-1 gp41
Title
Antimicrobial Peptide Resistance and Immunomodulation by HIV-1 gp41.
Creator
Wood, Matthew, Cole, Alexander, Chai, Karl, Teter, Kenneth, Parkinson, Christopher, University of Central Florida
Abstract / Description
Fusion inhibitors are a class of antiretroviral drugs used to prevent entry of HIV into host cells. Many of the fusion inhibitors being developed, including the drug enfuvirtide (ENF), are peptides designed to mimic, and thereby competitively inhibit, the viral fusion protein gp41. An exception to this is a class of cyclic, cationic, antimicrobial peptides known as ?-defensins, which are produced by many non-human primates and exhibit broad-spectrum antiviral and antibacterial activity....
Show moreFusion inhibitors are a class of antiretroviral drugs used to prevent entry of HIV into host cells. Many of the fusion inhibitors being developed, including the drug enfuvirtide (ENF), are peptides designed to mimic, and thereby competitively inhibit, the viral fusion protein gp41. An exception to this is a class of cyclic, cationic, antimicrobial peptides known as ?-defensins, which are produced by many non-human primates and exhibit broad-spectrum antiviral and antibacterial activity. Currently, the ?-defensin analog RC-101 is being developed as a microbicide to prevent sexual transmission of HIV-1. Understanding potential RC-101 resistance, and how resistance to other fusion inhibitors affects RC-101 susceptibility, is critical for future development.Partial drug resistance due to genetic variability within HIV-1 presents a major hurdle in microbicide development. Drug-resistance mutations, whether naturally occurring or resulting from selection during treatment, often apply to many drugs in a particular class. Combining different drug classes into a single microbicide should provide greater protection against the growing variability observed in HIV. Our work has identified the beneficial effects of combining the fusion inhibitor RC-101 and the RT inhibitor CSIC to prevent transmission of clinically isolated and drug-resistant HIV-1.Several aspects of HIV-1 virulence and pathogenesis are mediated by the envelope protein gp41. Additionally, peptides derived from the gp41 ectodomain have been shown to induce chemotaxis in monocytes and neutrophils. While this chemotactic activity has been characterized, it is not known how these peptides could be produced under biological conditions. Our findings demonstrate that the epithelial serine protease matriptase efficiently cleaves the gp41 HR1 region at conserved residues into a chemotactic peptide.Here, we present evidence that advances our understanding of resistance to peptide entry inhibitors, reveals a potential benefit to combining specific drugs in an antiviral microbicide, and identifies a pathway by which HIV-1 may generate peptides to exploit host immunity. This work thereby facilitates improved methods in countering drug resistance and the development of new antiviral approaches to prevent HIV-1 transmission. Additionally, we have revealed basic mechanistic evidence that shed light on our current understanding of HIV-1 infection. Specifically, our focus on gp41 provides much needed insight into its role in membrane fusion, drug susceptibility, and modification of host responses.
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Date Issued
2014
Identifier
CFE0005560, ucf:50286
Format
Document (PDF)
PURL
http://purl.flvc.org/ucf/fd/CFE0005560
The Influence of Stigma on Quality of Life and Relationship Satisfaction for Prostate Cancer Survivors and Their Partners
Title
The Influence of Stigma on Quality of Life and Relationship Satisfaction for Prostate Cancer Survivors and Their Partners.
Creator
Wood, Andrew, Barden, Sejal, Daire, Andrew, Lambie, Glenn, Munyon, Matthew, Conley, Abigail, University of Central Florida
Abstract / Description
The purpose of this study was to examine the relationships between stigma, quality of life (QoL), and relationships satisfaction for prostate cancer (PCa) survivors and their intimate and/or romantic partners. The investigator tested a theoretical model that stigma (as measured by the Social Impact Scale [SIS; Fife (&) Wright, 2000]) influenced QoL (as measured by the Functional Assessment of Cancer Therapy (-) Prostate [FACT-P; Esper et al., 1997] and the Functional Assessment of Cancer...
Show moreThe purpose of this study was to examine the relationships between stigma, quality of life (QoL), and relationships satisfaction for prostate cancer (PCa) survivors and their intimate and/or romantic partners. The investigator tested a theoretical model that stigma (as measured by the Social Impact Scale [SIS; Fife (&) Wright, 2000]) influenced QoL (as measured by the Functional Assessment of Cancer Therapy (-) Prostate [FACT-P; Esper et al., 1997] and the Functional Assessment of Cancer Therapy (-) General Population [FACT-GP; Cella et al., 1993]) and relationship satisfaction (as measured by the Couples Satisfaction Index [CSI; Funk (&) Rogge, 2007]) for both PCa survivors and their partners (N = 72 couples). The investigator hypothesized that stigma would have a negative influence on both QoL and relationship satisfaction. Further, exploratory research questions pertained to the influence of race on stigma, QoL, and relationship satisfaction, as well as examining difference in experiences of stigma based on demographic variables (e.g., age and income).The results of the structural equation model analyses identified that stigma negatively influenced QoL (R2 = .84, p (<) .05) and relationship satisfaction (R2 = .19, p (<) .05) for both PCa survivors and their partners. Race did not have statistically significant (p (>) .05) relationships with stigma, QoL, or relationship satisfaction and stigma was not found to be statistically different (p (>) .05) based on demographic variables. Implications of the results of the study include (a) practical implications for PCa survivors and their partners; (b) strategies for effective individual, group, and couples-based counseling; (c) need for counselor educators to prepare counselors to work with medically ill populations and cancer survivors; (d) PCa stigma instrument development; and (e) the necessity to examine research with couples in a dyadic fashion.
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Date Issued
2015
Identifier
CFE0005742, ucf:50112
Format
Document (PDF)
PURL
http://purl.flvc.org/ucf/fd/CFE0005742