The D-amino acid peptide D3 reduces amyloid fibril boosted HIV-1 infectivity

AIDS Research and Therapy

Heiner Schaal¹  Dieter Willbold¹  Susanne Aileen Funke²  Yeliz Cinar³  Antonia Nicole Klein³  Marek Widera⁴ 

[1]Biologisch und Medizinisches Forschungszentrum (BMFZ), Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany

[2]Bioanalytik, Fakultät für Angewandte Naturwissenschaften, Hochschule für Angewandte Wissenschaften Coburg, 96450 Coburg, Germany

[3]Forschungszentrum Jülich, ICS-6, Jülich, 52425, Germany

[4]Institut für Virologie, Heinrich-Heine-Universität, D-40225 Düsseldorf, Germany

关键词: Oligomers;    Monomers;    Drugs;    D-enantiomeric peptide;    Alzheimer’s disease;    Amyloid-beta;    D3;    SEVI;    HIV-1 infection;   

Others  :  789552
DOI  :  10.1186/1742-6405-11-1

 received in 2013-07-24, accepted in 2014-01-09,  发布年份 2014

【 摘 要 】

Background

Amyloid fibrils such as Semen-Derived Enhancer of Viral Infection (SEVI) or amyloid-β-peptide (Aβ) enhance HIV-1 attachment and entry. Inhibitors destroying or converting those fibrils into non-amyloidogenic aggregates effectively reduce viral infectivity. Thus, they seem to be suitable as therapeutic drugs expanding the current HIV-intervening repertoire of antiretroviral compounds.

Findings

In this study, we demonstrate that the small D-amino acid peptide D3, which was investigated for therapeutic studies on Alzheimer’s disease (AD), significantly reduces both SEVI and Aβ fibril boosted infectivity of HIV-1.

Conclusions

Since amyloids could play an important role in the progression of AIDS dementia complex (ADC), the treatment of HIV-1 infected individuals with D3, that inhibits Aβ fibril formation and converts preformed Aβ fibrils into non-amyloidogenic and non-fibrillar aggregates, may reduce the vulnerability of the central nervous system of HIV patients for HIV associated neurological disorders.

【 授权许可】

   
2014 Widera et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

【 参考文献 】

• [1]Luhrs T, Ritter C, Adrian M, Riek-Loher D, Bohrmann B, Dobeli H, Schubert D, Riek R: 3D structure of Alzheimer’s amyloid-beta(1–42) fibrils. Proc Natl Acad Sci USA 2005, 102:17342-17347.
• [2]Wojtowicz WM, Farzan M, Joyal JL, Carter K, Babcock GJ, Israel DI, Sodroski J, Mirzabekov T: Stimulation of enveloped virus infection by beta-amyloid fibrils. J Biol Chem 2002, 277:35019-35024.
• [3]Munch J, Rucker E, Standker L, Adermann K, Goffinet C, Schindler M, Wildum S, Chinnadurai R, Rajan D, Specht A, et al.: Semen-derived amyloid fibrils drastically enhance HIV infection. Cell 2007, 131:1059-1071.
• [4]Roan NR, Munch J, Arhel N, Mothes W, Neidleman J, Kobayashi A, Smith-McCune K, Kirchhoff F, Greene WC: The cationic properties of SEVI underlie its ability to enhance human immunodeficiency virus infection. J Virol 2009, 83:73-80.
• [5]Capule CC, Brown C, Olsen JS, Dewhurst S, Yang J: Oligovalent amyloid-binding agents reduce SEVI-mediated enhancement of HIV-1 infection. J Am Chem Soc 2012, 134:905-908.
• [6]Olsen JS, Brown C, Capule CC, Rubinshtein M, Doran TM, Srivastava RK, Feng C, Nilsson BL, Yang J, Dewhurst S: Amyloid-binding small molecules efficiently block SEVI (semen-derived enhancer of virus infection)- and semen-mediated enhancement of HIV-1 infection. J Biol Chem 2010, 285:35488-35496.
• [7]Hauber I, Hohenberg H, Holstermann B, Hunstein W, Hauber J: The main green tea polyphenol epigallocatechin-3-gallate counteracts semen-mediated enhancement of HIV infection. Proc Natl Acad Sci USA 2009, 106:9033-9038.
• [8]Sievers SA, Karanicolas J, Chang HW, Zhao A, Jiang L, Zirafi O, Stevens JT, Munch J, Baker D, Eisenberg D: Structure-based design of non-natural amino-acid inhibitors of amyloid fibril formation. Nature 2011, 475:96-100.
• [9]Roan NR, Sowinski S, Munch J, Kirchhoff F, Greene WC: Aminoquinoline surfen inhibits the action of SEVI (semen-derived enhancer of viral infection). J Biol Chem 2010, 285:1861-1869.
• [10]Funke AS, van Groen T, Kadish I, Bartnik D, Nagel-Steger L, Brener O, Sehl T, Batra-Safferling R, Moriscot C, Schoehn G, et al.: Oral treatment with the d-enantiomeric peptide D3 improves the pathology and behavior of Alzheimer’s disease transgenic mice. ACS Chem Neurosci 2010, 1:639-648.
• [11]Polzer S, Dittmar MT, Schmitz H, Schreiber M: The N-linked glycan g15 within the V3 loop of the HIV-1 external glycoprotein gp120 affects coreceptor usage, cellular tropism, and neutralization. Virology 2002, 304:70-80.
• [12]Chien P, Weissman JS, DePace AH: Emerging principles of conformation-based prion inheritance. Annu Rev Biochem 2004, 73:617-656.
• [13]Daniel MD, Li Y, Naidu YM, Durda PJ, Schmidt DK, Troup CD, Silva DP, MacKey JJ, Kestler HW 3rd, Sehgal PK, et al.: Simian immunodeficiency virus from African green monkeys. J Virol 1988, 62:4123-4128.
• [14]Kikukawa R, Koyanagi Y, Harada S, Kobayashi N, Hatanaka M, Yamamoto N: Differential susceptibility to the acquired immunodeficiency syndrome retrovirus in cloned cells of human leukemic T-cell line Molt-4. J Virol 1986, 57:1159-1162.
• [15]Abacioglu YH, Fouts TR, Laman JD, Claassen E, Pincus SH, Moore JP, Roby CA, Kamin-Lewis R, Lewis GK: Epitope mapping and topology of baculovirus-expressed HIV-1 gp160 determined with a panel of murine monoclonal antibodies. AIDS Res Hum Retroviruses 1994, 10:371-381.
• [16]Widera M, Erkelenz S, Hillebrand F, Krikoni A, Widera D, Kaisers W, Deenen R, Gombert M, Dellen R, Pfeiffer T, et al.: An intronic G run within HIV-1 intron 2 is critical for splicing regulation of vif mRNA. J Virol 2013, 87:2707-2720.
• [17]van Groen T, Wiesehan K, Funke SA, Kadish I, Nagel-Steger L, Willbold D: Reduction of Alzheimer’s disease amyloid plaque load in transgenic mice by D3, A D-enantiomeric peptide identified by mirror image phage display. Chem Med Chem 2008, 3:1848-1852.
• [18]Shen R, Richter HE, Smith PD: Early HIV-1 target cells in human vaginal and ectocervical mucosa. Am J Reprod Immunol 2011, 65:261-267.