Retrovirology | |
Effect of semen and seminal amyloid on vaginal transmission of simian immunodeficiency virus | |
Frank Kirchhoff2  Christiane Stahl-Hennig1  Katharina Raue1  Maral Yolamanova2  Ulrike Sauermann1  Jan Münch2  | |
[1] German Primate Centre, 37077 Göttingen, Germany;Ulm Peptide Pharmaceuticals, Ulm University Medical Center, Meyerhofstrasse 1, 89081 Ulm, Germany | |
关键词: Rhesus macaque; Transmission; SIV; Amyloid; SEVI; Semen-mediated enhancement of viral infection; | |
Others : 805940 DOI : 10.1186/1742-4690-10-148 |
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received in 2013-10-17, accepted in 2013-11-27, 发布年份 2013 | |
【 摘 要 】
Background
Semen and semen-derived amyloid fibrils boost HIV infection in vitro but their impact on sexual virus transmission in vivo is unknown. Here, we examined the effect of seminal plasma (SP) and semen-derived enhancer of virus infection (SEVI) on vaginal virus transmission in the SIV/rhesus macaque (Macacca mulatta) model.
Results
A total of 18 non-synchronized female rhesus macaques (six per group) were exposed intra-vaginally to increasing doses of the pathogenic SIVmac239 molecular clone in the presence or absence of SEVI and SP. Establishment of productive virus infection was assessed by measuring plasma viral RNA loads at weekly intervals. We found that the first infections occurred at lower viral doses in the presence of SP and SEVI compared to the control group. Furthermore, the average peak viral loads during acute infection were about 6-fold higher after exposure to SP- and SEVI-treated virus. Overall infection rates after a total of 27 intra-vaginal exposures to increasing doses of SIV, however, were similar in the absence (4 of 6 animals) and presence of SP (5 of 6), or SEVI (4 of 6). Furthermore, the infectious viral doses required for infection varied considerably and did not differ significantly between these three groups.
Conclusions
Semen and SEVI did not have drastic effects on vaginal SIV transmission in the present experimental setting but may facilitate spreading of virus infection after exposure to low viral doses that most closely approximate the in vivo situation.
【 授权许可】
2013 Münch et al.; licensee BioMed Central Ltd.
【 预 览 】
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【 参考文献 】
- [1]United Nations: UNAIDS 2013 report of the global AIDS epidemic. 2013. http://www.unaids.org/en/media/unaids/contentassets/documents/epidemiology/2013/gr2013/UNAIDS_Global_Report_2013_en.pdf webcite
- [2]Quinn TC, Overbaugh J: HIV/AIDS in women: an expanding epidemic. Science 2005, 308:1582-1583.
- [3]Royce RA, Sena A, Cates W Jr, Cohen MS: Sexual transmission of HIV. N Engl J Med 1997, 336:1072-1078.
- [4]Gray RH, Wawer MJ, Brookmeyer R, Sewankambo NK, Serwadda D, Wabwire-Mangen F, Lutalo T, Li X, van Cott T, Quinn TC, Rakai Project Team: Probability of HIV-1 transmission per coital act in monogamous, heterosexual, HIV-1-discordant couples in Rakai, Uganda. Lancet 2001, 357:1149-1153.
- [5]Boily MC, Baggaley RF, Wang L, Masse B, White RG, Hayes RJ, Alary M: Heterosexual risk of HIV-1 infection per sexual act: systematic review and meta-analysis of observational studies. Lancet Infect Dis 2009, 9:118-129.
- [6]Chakraborty H, Sen PK, Helms RW, Vernazza PL, Fiscus SA, Eron JJ, Patterson BK, Coombs RW, Krieger JN, Cohen MS: Viral burden in genital secretions determines male-to-female sexual transmission of HIV-1: a probabilistic empiric model. AIDS 2001, 15:621-627.
- [7]Gupta P, Mellors J, Kingsley L, Riddler S, Singh MK, Schreiber S, Cronin M, Rinaldo CR: High viral load in semen of human immunodeficiency virus type 1-infected men at all stages of disease and its reduction by therapy with protease and nonnucleoside reverse transcriptase inhibitors. J Virol 1997, 71:6271-6275.
- [8]Pilcher CD, Tien HC, Eron JJ Jr, Vernazza PL, Leu SY, Stewart PW, Goh LE, Cohen MS, Quest Study: Brief but efficient: acute HIV infection and the sexual transmission of HIV. J Inf Dis 2004, 189:1785-1792.
- [9]Bouhlal H, Chomont N, Haeffner-Cavaillon N, Kazatchkine MD, Belec L, Hocini H: Opsonization of HIV-1 by semen complement enhances infection of human epithelial cells. J Immunol 2002, 169:3301-3306.
- [10]Münch J, Rücker E, Ständker L, Adermann K, Goffinet C, Schindler M, Wildum S, Chinnadurai R, Rajan D, Specht A, Giménez-Gallego G, Sánchez PC, Fowler DM, Koulov A, Kelly JW, Mothes W, Grivel JC, Margolis L, Keppler OT, Forssmann WG, Kirchhoff F: Semen-derived amyloid fibrils drastically enhance HIV infection. Cell 2007, 131:1059-1071.
- [11]Arnold F, Schnell J, Zirafi O, Stürzel C, Meier C, Weil T, Ständker L, Forssmann WG, Roan NR, Greene WC, Kirchhoff F, Münch J: Naturally occurring fragments from two distinct regions of the prostatic acid phosphatase form amyloidogenic enhancers of HIV infection. J Virol 2012, 86:1244-1249.
- [12]Roan NR, Müller JA, Liu H, Chu S, Arnold F, Stürzel CM, Walther P, Dong M, Witkowska HE, Kirchhoff F, Münch J, Greene WC: Peptides released by physiological cleavage of semen coagulum proteins form amyloids that enhance HIV infection. Cell Host Microbe 2011, 10:541-550.
- [13]Kim KA, Yolamanova M, Zirafi O, Roan NR, Staendker L, Forssmann WG, Burgener A, Dejucq-Rainsford N, Hahn BH, Shaw GM, Greene WC, Kirchhoff F, Münch J: Semen-mediated enhancement of HIV infection is donor-dependent and correlates with the levels of SEVI. Retrovirology 2010, 7:55. BioMed Central Full Text
- [14]Roan NR, Münch 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.
- [15]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.
- [16]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.
- [17]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.
- [18]Sievers SA, Karanicolas J, Chang HW, Zhao A, Jiang L, Zirafi O, Stevens JT, Münch J, Baker D, Eisenberg D: Structure-based design of non-natural amino-acid inhibitors of amyloid fibril formation. Nature 2011, 475:96-100.
- [19]Yolamanova M, Meier C, Shaytan AK, Vas V, Bertoncini CW, Arnold F, Zirafi O, Usmani SM, Müller JA, Sauter D, Goffinet C, Palesch D, Walther P, Roan NR, Geiger H, Lunov O, Simmet T, Bohne J, Schrezenmeier H, Schwarz K, Ständker L, Forssmann WG, Salvatella X, Khalatur PG, Khokhlov AR, Knowles TP, Weil T, Kirchhoff F, Münch J: Peptide nanofibrils boost retroviral gene transfer and provide a rapid means for concentrating viruses. Nat Nanotechnol 2013, 8:130-136.
- [20]Haase AT: Targeting early infection to prevent HIV-1 mucosal transmission. Nature 2010, 464:217-223.
- [21]Haase AT: Early events in sexual transmission of HIV and SIV and opportunities for interventions. Annu Rev Med 2011, 62:127-139.
- [22]Pöhlmann S, Lee B, Meister S, Krumbiegel M, Leslie G, Doms RW, Kirchhoff F: Simian immunodeficiency virus utilizes human and Sooty Mangabey but not Rhesus Macaque STRL33 for efficient entry. J Virol 2000, 74:5075-5082.
- [23]Robertson SA, Ingman WV, O’Leary S, Sharkey DJ, Tremellen KP: Transforming growth factor beta–a mediator of immune deviation in seminal plasma. J Reprod Immunol 2002, 57:109-128.
- [24]Sharkey DJ, Macpherson AM, Tremellen KP, Robertson SA: Seminal plasma differentially regulates inflammatory cytokine gene expression in human cervical and vaginal epithelial cells. Mol Hum Reprod 2007, 13:491-501.
- [25]Sharkey DJ, Tremellen KP, Jasper MJ, Gemzell-Danielsson K, Robertson SA: Seminal fluid induces leukocyte recruitment and cytokine and chemokine mRNA expression in the human cervix after coitus. J Immunol 2012, 188:2445-2454.
- [26]Robertson SA: Seminal plasma and male factor signalling in the female reproductive tract. Cell Tissue Res 2005, 322:43-52.
- [27]Robertson SA, Sharkey DJ: The role of semen in induction of maternal immune tolerance to pregnancy. Semin Immunol 2001, 13:243-254.
- [28]Clark GF, Schust DJ: Manifestations of immune tolerance in the human female reproductive tract. Front Immunol 2013, 4:26.
- [29]Neildez O, Le Grand R, Chéret A, Caufour P, Vaslin B, Matheux F, Théodoro F, Roques P, Dormont D: Variation in virological parameters and antibody responses in macaques after atraumatic vaginal exposure to a pathogenic primary isolate of SIVmac251. Res Virol 1998, 149:53-68.
- [30]Miller CJ, Marthas M, Torten J, Alexander NJ, Moore JP, Doncel GF, Hendrickx AG: Intravaginal inoculation of rhesus macaques with cell-free simian immunodeficiency virus results in persistent or transient viremia. J Virol 1994, 68:6391-6400.
- [31]Kirmaier A, Wu F, Newman RM, Hall LR, Morgan JS, O’Connor S, Marx PA, Meythaler M, Goldstein S, Buckler-White A, Kaur A, Hirsch VM, Johnson WE: TRIM5 suppresses cross-species transmission of a primate immunodeficiency virus and selects for emergence of resistant variants in the new species. PLoS Biol 2010, 8(8):e1000462.
- [32]Naidu YM, Kestler HW 3rd, Li Y, Butler CV, Silva DP, Schmidt DK, Troup CD, Sehgal PK, Sonigo P, Daniel MD, et al.: Characterization of infectious molecular clones of simian immunodeficiency virus (SIVmac) and human immunodeficiency virus type 2: persistent infection of rhesus monkeys with molecularly cloned SIVmac. J Virol 1988, 62:4691-4696.
- [33]Vishwanathan SA, Guenthner PC, Lin CY, Dobard C, Sharma S, Adams DR, Otten RA, Heneine W, Hendry RM, McNicholl JM, Kersh EN: High susceptibility to repeated, low-dose, vaginal SHIV exposure late in the luteal phase of the menstrual cycle of pigtail macaques. J Acquir Immune Defic Syndr 2011, 57:261-264.
- [34]Spear G, Rothaeulser K, Fritts L, Gillevet PM, Miller CJ: In captive rhesus macaques, cervicovaginal inflammation is common but not associated with the stable polymicrobial microbiome. PLoS One 2012, 7:e52992.
- [35]Stolte-Leeb N, Loddo R, Antimisiaris S, Schultheiss T, Sauermann U, Franz M, Mourtas S, Parsy C, Storer R, La Colla P, Stahl-Hennig C: Topical nonnucleoside reverse transcriptase inhibitor MC 1220 partially prevents vaginal RT-SHIV infection of macaques. AIDS Res Hum Retroviruses 2011, 27:933-943.
- [36]Negri DR, Baroncelli S, Catone S, Comini A, Michelini Z, Maggiorella MT, Sernicola L, Crostarosa F, Belli R, Mancini MG, Farcomeni S, Fagrouch Z, Ciccozzi M, Boros S, Liljestrom P, Norley S, Heeney J, Titti F: Protective efficacy of a multicomponent vector vaccine in cynomolgus monkeys after intrarectal simian immunodeficiency virus challenge. J Gen Virol 2004, 85:1191-1201.