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Logo of aidsrestherBioMed CentralBiomed Central Web Sitesearchsubmit a manuscriptregisterthis articleAIDS Research and Therapy
 
AIDS Res Ther. 2012; 9: 2.
Published online Jan 19, 2012. doi:  10.1186/1742-6405-9-2
PMCID: PMC3308922
Assessment of the range of the HIV-1 infectivity enhancing effect of individual human semen specimen and the range of inhibition by EGCG
Philip Hartjen,#1,3 Sebastian Frerk,#1,3 Ilona Hauber,3 Verena Matzat,1,3 Adriana Thomssen,1,3 Barbara Holstermann,3 Heinrich Hohenberg,3 Wolfgang Schulze,2 Julian Schulze zur Wiesch,#1,3 and Jan van Lunzencorresponding author#1,3
1Infectious Diseases Unit, I. Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20251 Hamburg, Germany
2Department of Andrology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20251 Hamburg, Germany
3Heinrich Pette Institute - Leibniz Institute for Experimental Virology (HPI), Martinistrasse 52, 20251 Hamburg, Germany
corresponding authorCorresponding author.
#Contributed equally.
Philip Hartjen: philip.hartjen/at/gmail.com; Sebastian Frerk: sfrerk/at/googlemail.com; Ilona Hauber: ilona.hauber/at/hpi.uni-hamburg.de; Verena Matzat: verenamatzat/at/googlemail.com; Adriana Thomssen: a.thomssen/at/googlemail.com; Barbara Holstermann: barbara.holstermann/at/hpi.uni-hamburg.de; Heinrich Hohenberg: heinz.hohenberg/at/hpi.uni-hamburg.de; Wolfgang Schulze: w.schulze/at/uke.uni-hamburg.de; Julian Schulze zur Wiesch: julianszw/at/googlemail.com; Jan van Lunzen: v.lunzen/at/uke.de
Received June 3, 2011; Accepted January 19, 2012.
Abstract
Recently, it has been shown that human ejaculate enhances human immunodeficiency virus 1 (HIV-1) infectivity. Enhancement of infectivity is conceived to be mediated by amyloid filaments from peptides that are proteolytically released from prostatic acid phosphatase (PAP), termed Semen-derived Enhancer of Virus Infection (SEVI). The aim of this study was to test the range of HIV-1 infectivity enhancing properties of a large number of individual semen samples (n = 47) in a TZM-bl reporter cell HIV infection system. We find that semen overall increased infectivity to 156% of the control experiment without semen, albeit with great inter- and intraindividual variability (range -53%-363%). Using transmission electron microscopy, we provide evidence for SEVI fibrils in fresh human semen for the first time. Moreover, we confirm that the infectivity enhancing property can be inhibited by the major green tea ingredient epigallocatechin-3-gallate (EGCG) at non-toxic concentrations. The median inhibition of infection by treatment with 0.4 mM EGCG was 70.6% (p < 0.0001) in our cohort. Yet, there were substantial variations of inhibition and in a minority of samples, infectivity enhancement was not inhibited by EGCG treatment at all. Thus, topical application of EGCG may be a feasible additional measure to prevent the sexual transmission of HIV. However, the reasons for the variability in the efficacy of the abrogation of semen-mediated enhancement of HIV-1 infectivity and EGCG efficacy have to be elucidated before therapeutic trials can be conducted.
Keywords: Semen, SEVI, EGCG, HIV transmission, microbicide
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