Blocking semen-mediated enhancement of HIV infection by amyloid-binding small molecules

被引:4
作者
Kirchhoff, Frank [1 ]
Muench, Jan [1 ]
机构
[1] Univ Hosp Ulm, Inst Mol Virol, D-89081 Ulm, Germany
关键词
amyloid; BTA-EG(6); HIV-1; Infectivity enhancement; microbicide; semen; SEVI; sexual transmission; thioflavin T; TRANSMISSION; VIRUS; SEVI; FIBRILS; CELLS;
D O I
10.2217/FVL.10.91
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Evaluation of: Olsen JS, Brown C, Capule CC et al.: Amyloid-binding small molecules efficiently block SEVI (semen-derived enhancer of virus infection)and semen-mediated enhancement of HIV-1 infection. J. Biol. Chem. 285(46), 35488-35496 (2010). Sexual intercourse is the major route for the spread of the AIDS pandemic and semen represents the main vector for HIV-1 transmission. It is under debate whether semen enhances or inhibits HIV-1 infection. However, accumulating evidence suggests that semen contains amyloid aggregates (termed 'semen-derived enhancer of virus infection' (SEVI)) that boost infection and thus represent a promising target for the prevention of HIV-1 transmission. Here, Olsen and colleagues demonstrate that BTA-EG6, a derivative of the amyloid-specific dye thioflavin T, binds SEVI fibrils. This interaction blocks the ability of SEVI to enhance virus infection by preventing the association of SEVI with target cells. Importantly, the authors also demonstrate that BTA-EG6 inhibits semen-mediated enhancement of HIV-1 infection without causing inflammation or toxicity in cervical cells. These results suggest that small amyloid-binding molecules that block semen-mediated enhancement of HIV-1 infection are a useful supplement to microbicides for preventing sexual transmission of the virus.
引用
收藏
页码:183 / 186
页数:4
相关论文
共 17 条
  • [1] Semen Protects CD4+ Target Cells from HIV Infection but Promotes the Preferential Transmission of R5 Tropic HIV
    Balandya, Emmanuel
    Sheth, Siddharth
    Sanders, Katherine
    Wieland-Alter, Wendy
    Lahey, Timothy
    [J]. JOURNAL OF IMMUNOLOGY, 2010, 185 (12) : 7596 - 7604
  • [2] Spermatozoa capture HIV-1 through heparan sulfate and efficiently transmit the virus to dendritic cells
    Ceballos, Ana
    Remes Lenicov, Federico
    Sabatte, Juan
    Rodriguez Rodrigues, Christian
    Cabrini, Mercedes
    Jancic, Carolina
    Raiden, Silvina
    Donaldson, Monica
    Agustin Pasqualini, Rodolfo, Jr.
    Marin-Briggiler, Clara
    Vazquez-Levin, Monica
    Capani, Francisco
    Amigorena, Sebastian
    Geffner, Jorge
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 2009, 206 (12) : 2717 - 2733
  • [3] Role of Semen in HIV-1 Transmission: Inhibitor or facilitator?
    Doncel, Gustavo F.
    Joseph, Theresa
    Thurman, Andrea R.
    [J]. AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, 2011, 65 (03) : 292 - 301
  • [4] The role of sexually transmitted diseases in HIV transmission
    Galvin, SR
    Cohen, MS
    [J]. NATURE REVIEWS MICROBIOLOGY, 2004, 2 (01) : 33 - 42
  • [5] Probability of HIV-1 transmission per coital act in monogamous, heterosexual, HIV-1-discordant couples in Rakai, Uganda
    Gray, RH
    Wawer, MJ
    Brookmeyer, R
    Sewankambo, NK
    Serwadda, D
    Wabwire-Mangen, F
    Lutalo, T
    Li, XB
    vanCott, T
    Quinn, TC
    [J]. LANCET, 2001, 357 (9263) : 1149 - 1153
  • [6] The main green tea polyphenol epigallocatechin-3-gallate counteracts semen-mediated enhancement of HIV infection
    Hauber, Ilona
    Hohenberg, Heinrich
    Holstermann, Barbara
    Hunstein, Werner
    Hauber, Joachim
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (22) : 9033 - 9038
  • [7] Fibrils of Prostatic Acid Phosphatase Fragments Boost Infections with XMRV (Xenotropic Murine Leukemia Virus-Related Virus), a Human Retrovirus Associated with Prostate Cancer
    Hong, Seunghee
    Klein, Eric A.
    Das Gupta, Jaydip
    Hanke, Kirsten
    Weight, Christopher J.
    Nguyen, Carvell
    Gaughan, Christina
    Kim, Kyeong-Ae
    Bannert, Norbert
    Kirchhoff, Frank
    Munch, Jan
    Silverman, Robert H.
    [J]. JOURNAL OF VIROLOGY, 2009, 83 (14) : 6995 - 7003
  • [8] Oligo(ethylene glycol) derivatives of thioflavin T as inhibitors of protein-amyloid interactions
    Inbar, Petra
    Li, Cui Q.
    Takayama, Stacy A.
    Bautista, Mahealani R.
    Yang, Jerry
    [J]. CHEMBIOCHEM, 2006, 7 (10) : 1563 - 1566
  • [9] Identification and characterisation of transmitted and early founder virus envelopes in primary HIV-1 infection
    Keele, Brandon F.
    Giorgi, Elena E.
    Salazar-Gonzalez, Jesus F.
    Decker, Julie M.
    Pham, Kimmy T.
    Salazar, Maria G.
    Sun, Chuanxi
    Grayson, Truman
    Wang, Shuyi
    Li, Hui
    Wei, Xiping
    Jiang, Chunlai
    Kirchherr, Jennifer L.
    Gao, Feng
    Anderson, Jeffery A.
    Ping, Li-Hua
    Swanstrom, Ronald
    Tomaras, Georgia D.
    Blattner, William A.
    Goepfert, Paul A.
    Kilby, J. Michael
    Saag, Michlael S.
    Delwart, Eric L.
    Busch, Michael P.
    Cohen, Myron S.
    Montefiori, David C.
    Haynes, Barton F.
    Gaschen, Brian
    Athreya, Gayathri S.
    Lee, Ha Y.
    Wood, Natasha
    Seoighe, Cathal
    Perelson, Alan S.
    Bhattacharya, Tanmoy
    Korber, Bette T.
    Hahn, Beatrice H.
    Shaw, George M.
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (21) : 7552 - 7557
  • [10] Semen-mediated enhancement of HIV infection is donor-dependent and correlates with the levels of SEVI
    Kim, Kyeong-Ae
    Yolamanova, Maral
    Zirafi, Onofrio
    Roan, Nadia R.
    Staendker, Ludger
    Forssmann, Wolf-Georg
    Burgener, Adam
    Dejucq-Rainsford, Nathalie
    Hahn, Beatrice H.
    Shaw, George M.
    Greene, Warner C.
    Kirchhoff, Frank
    Muench, Jan
    [J]. RETROVIROLOGY, 2010, 7