Repeated semen exposure decreases cervicovaginal SIVmac251 infection in rhesus macaques

被引：3

作者：

Abdulhaqq, Shaheed A. ^{[1
]}

Martinez, Melween ^{[2
,3
]}

Kang, Guobin ^{[4
]}

Rodriguez, Idia, V ^{[2
,3
]}

Nichols, Stephanie M. ^{[2
,3
]}

Beaumont, David ^{[5
,6
]}

Joseph, Jocelin ^{[1
]}

Azzoni, Livio ^{[1
]}

Yin, Xiangfan ^{[1
]}

Wise, Megan ^{[1
]}

Weiner, David ^{[1
]}

Liu, Qin ^{[1
]}

Foulkes, Andrea ^{[7
]}

Muench, Jan ^{[8
]}

Kirchhoff, Frank ^{[8
]}

Coutifaris, Christos ^{[9
]}

Tomaras, Georgia D. ^{[5
,6
]}

Sariol, Carlos ^{[2
,3
]}

Marx, Preston A. ^{[10
,11
]}

Li, Qingsheng ^{[4
]}

Kraiselburd, Edmundo N. ^{[2
,3
]}

Montane, Luis J. ^{[1
]}

机构：

[1] Wistar Inst Anat & Biol, 3601 Spruce St, Philadelphia, PA 19104 USA

[2] Univ Puerto Rico, Caribbean Primate Res Ctr, San Juan, PR 00936 USA

[3] Univ Puerto Rico, Anim Resources Ctr, San Juan, PR 00936 USA

[4] Univ Nebraska, Sch Biol Sci, Lincoln, NE USA

[5] Duke Univ, Duke Human Vaccine Inst, Durham, NC USA

[6] Duke Univ, Dept Surg Immunol & Mol Genet & Microbiol, Durham, NC USA

[7] Mt Holyoke Coll, S Hadley, MA 01075 USA

[8] Ulm Univ, Inst Mol Virol, Med Ctr, Ulm, Germany

[9] Univ Penn, Philadelphia, PA 19104 USA

[10] Tulane Univ, Sch Publ Hlth & Trop Med, Tulane Natl Primate Res Ctr, New Orleans, LA 70118 USA

[11] Tulane Univ, Sch Publ Hlth & Trop Med, Dept Trop Med, New Orleans, LA 70118 USA

来源：

NATURE COMMUNICATIONS | 2019年 / 10卷 / 1期

关键词：

REGULATORY T-CELLS; SIV VAGINAL TRANSMISSION; ESTROGEN PROTECTS; HIV-1; INFECTION; SEMINAL FLUID; ACTIVATION; EXPRESSION; PREVENTION; PHENOTYPE; RESISTANT;

D O I：

10.1038/s41467-019-11814-5

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Semen is the vehicle for virion dissemination in the female reproductive tract (FRT) in male-to-female HIV transmission. Recent data suggests that higher frequency semen exposure is associated with activation of anti-HIV mechanisms in HIV negative sex workers. Here, we use a non-human primate (NHP) model to show that repeated vaginal exposure to semen significantly reduces subsequent infection by repeated low-dose vaginal SIVmac251 challenge. Repeated semen exposures result in lower CCR5 expression in circulating CD4+ T-cells, as well as higher expression of Mx1 (in correlation with IFN epsilon expression) and FoxP3 in the cervicovaginal mucosa, and increased infiltration of CD4+ T-cells. Establishing in vivo evidence of competing effects of semen on transmission impacts our basic understanding of what factors may determine HIV infectivity in humans. Our results clearly indicate that repeated semen exposure can profoundly modulate the FRT microenvironment, paradoxically promoting host resistance against HIV acquisition.

引用

页数：10

共 39 条

[11] Non-Human Primate Regulatory T Cells: Current Biology and Implications for Transplantation [J].

Dons, Eefje M. ;

Raimondi, Giorgio ;

Cooper, David K. C. ;

Thomson, Angus W. .

TRANSPLANTATION, 2010, 90 (08) :811-816

[12] Interferon-ε Protects the Female Reproductive Tract from Viral and Bacterial Infection [J].

Fung, Ka Yee ;

Mangan, Niamh E. ;

Cumming, Helen ;

Horvat, Jay C. ;

Mayall, Jemma R. ;

Stifter, Sebastian A. ;

De Weerd, Nicole ;

Roisman, Laila C. ;

Rossjohn, Jamie ;

Robertson, Sarah A. ;

Schjenken, John E. ;

Parker, Belinda ;

Gargett, Caroline E. ;

Nguyen, Hong P. T. ;

Carr, Daniel J. ;

Hansbro, Philip M. ;

Hertzog, Paul J. .

SCIENCE, 2013, 339 (6123) :1088-1092

[13] Interferon epsilon promotes HIV restriction at multiple steps of viral replication [J].

Garcia-Minambres, Albert ;

Eid, Sahar G. ;

Mangan, Niamh E. ;

Pade, Corinna ;

Lim, San S. ;

Matthews, Antony Y. ;

de Weerd, Nicole A. ;

Hertzog, Paul J. ;

Mak, Johnson .

IMMUNOLOGY AND CELL BIOLOGY, 2017, 95 (05) :478-483

[14] Probability of HIV-1 transmission per coital act in monogamous, heterosexual, HIV-1-discordant couples in Rakai, Uganda [J].

Gray, RH ;

Wawer, MJ ;

Brookmeyer, R ;

Sewankambo, NK ;

Serwadda, D ;

Wabwire-Mangen, F ;

Lutalo, T ;

Li, XB ;

vanCott, T ;

Quinn, TC .

LANCET, 2001, 357 (9263) :1149-1153

[15] Molecular typing of major histocompatibility complex class I alleles in the Indian rhesus macaque which restrict SIVCD8+ T cell epitopes [J].

Kaizu, Masahiko ;

Borchardt, Gretta J. ;

Glidden, Chrystal E. ;

Fisk, Debra L. ;

Loffredo, John T. ;

Watkins, David I. ;

Rehrauer, William M. .

IMMUNOGENETICS, 2007, 59 (09) :693-703

[16] Late seroconversion in HIV-resistant Nairobi prostitutes despite pre-existing HIV-specific CD8+ responses [J].

Kaul, R ;

Rowland-Jones, SL ;

Kimani, J ;

Dong, T ;

Yang, HB ;

Kiama, P ;

Rostron, T ;

Njagi, E ;

Bwayo, JJ ;

MacDonald, KS ;

McMichael, AJ ;

Plummer, FA .

JOURNAL OF CLINICAL INVESTIGATION, 2001, 107 (03) :341-349

[17] Antiinflammatory profiles during primary SIV infection in African green monkeys are associated with protection against AIDS [J].

Kornfeld, C ;

Ploquin, MJY ;

Pandrea, I ;

Faye, A ;

Onanga, R ;

Apetrei, C ;

Poaty-Mavoungou, V ;

Rouquet, P ;

Estaquier, J ;

Mortara, L ;

Desoutter, JF ;

Butor, C ;

Le Grand, R ;

Roques, P ;

Simon, F ;

Barré-Sinoussi, F ;

Diop, OM ;

Müller-Trutwin, MC .

JOURNAL OF CLINICAL INVESTIGATION, 2005, 115 (04) :1082-1091

[18]

KRAISELBURD EN, 1995, CELL MOL BIOL, V41, pS41

[19] Human immunodeficiency virus type 1 envelope epitope-specific CD4+ T lymphocytes in simian/human immunodeficiency virus-infected and vaccinated rhesus monkeys detected using a peptide-major histocompatibility complex class II tetramer [J].

Kuroda, MJ ;

Schmitz, JE ;

Lekutis, C ;

Nickerson, CE ;

Lifton, MA ;

Franchini, G ;

Harouse, JM ;

Cheng-Mayer, C ;

Letvin, NL .

JOURNAL OF VIROLOGY, 2000, 74 (18) :8751-8756

[20] HIV sexual transmission risk among serodiscordant couples: assessing the effects of combining prevention strategies [J].

Lasry, Arielle ;

Sansom, Stephanie L. ;

Wolitski, Richard J. ;

Green, Timothy A. ;

Borkowf, Craig B. ;

Patel, Pragna ;

Mermin, Jonathan .

AIDS, 2014, 28 (10) :1521-1529

← 1 2 3 4 →