INFECTION OF VAGINAL AND COLONIC EPITHELIAL-CELLS BY THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 IS NEUTRALIZED BY ANTIBODIES RAISED AGAINST CONSERVED EPITOPES IN THE ENVELOPE GLYCOPROTEIN GP120

被引:73
|
作者
FURUTA, Y
ERIKSSON, K
SVENNERHOLM, B
FREDMAN, P
HORAL, P
JEANSSON, S
VAHLNE, A
HOLMGREN, J
CZERKINSKY, C
机构
[1] GOTHENBURG UNIV,DEPT MED MICROBIOL & IMMUNOL,S-41346 GOTHENBURG,SWEDEN
[2] GOTHENBURG UNIV,DEPT CLIN VIROL,S-41346 GOTHENBURG,SWEDEN
[3] GOTHENBURG UNIV,DEPT NEUROCHEM,S-41346 GOTHENBURG,SWEDEN
[4] ULLEVAL UNIV HOSP,DEPT MICROBIOL,DIV LAB MED,N-0407 OSLO,NORWAY
[5] HUDDINGE UNIV HOSP,KAROLINSKA INST,DIV CLIN VIROL,S-14186 HUDDINGE,SWEDEN
[6] INSERM,U80,F-69008 LYON,FRANCE
关键词
VIRUS RECEPTORS; GLYCOSPHINGOLIPIDS; PEPTIDE ANTISERA; EPITHELIUM; MUCOSA;
D O I
10.1073/pnas.91.26.12559
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
The rectal and genital tract mucosae are considered to be major sites of entry for the human immuno-deficiency virus (HIV) during sexual contact. We now demonstrate that vaginal epithelial cell can be infected by HIV type 1 (HIV-1) via a mechanism similar to that described for neuroglial cells and, more recently, for colorectal epithelial cells, involving initial interaction of the HIV-1 envelope glycoprotein gp120 with a cell-surface glycosphingolipid (sulfated lactosylceramide). A hyperimmune serum against gp120 was able to neutralize HIV-1 infection of vaginal epithelial cells. Site-directed immunization was employed to identify sites on gp120 recognized by antibodies neutralizing HIV-1 infection of vaginal colonic epithelial cells. Hyperimmune sera were raised in monkeys against a series of 40 overlapping synthetic peptides covering the entire sequence of HIV-1 (HTLV-IIIB) gp120. Antisera raised against five synthetic peptides, corresponding to three relatively conserved regions and to the hypervariable region (V3 loop), efficiently neutralized HIV-1 infection of human vaginal epithelial cells in vitro. Similar results were obtained with the colonic cells. Hyperimmune sera to all five peptides have been shown earlier to neutralize HIV-1 infectivity in CD4(+) T cells. These results have obvious implications for the design of mucosal subunit vaccines against sexually transmitted HIV-1 infections.
引用
收藏
页码:12559 / 12563
页数:5
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