Virus-Like Particles Carrying HIV-1 Env with a Modulated Glycan Composition

被引:0
作者
Kaevitser, G. A. [1 ]
Samokhvalov, E. I. [1 ]
Scheblyakov, D. V. [1 ]
Gintsburg, A. L. [1 ,2 ]
Vzorov, A. N. [1 ,3 ]
机构
[1] Gamaleya Fed Res Ctr Epidemiol & Microbiol, Moscow 123098, Russia
[2] Minist Hlth Russian Federat, Sechenov First Moscow State Med Univ, Moscow 123098, Russia
[3] Moscow MV Lomonosov State Univ, Fac Biol, Dept Immunol, Moscow 119234, Russia
关键词
HIV-1; Env; glycoprotein; glycans; VLP; recombinant vaccinia virus; CHO cells; N-LINKED GLYCOSYLATION; NEUTRALIZATION SENSITIVITY; ENVELOPE GLYCOPROTEIN; CYTOPLASMIC DOMAIN; CD4; INDEPENDENCE; FULL-LENGTH; V3; LOOP; GP120; RECEPTOR; IMMUNOGENICITY;
D O I
10.1134/S0026893324700341
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Previously obtained highly immunogenic Env-VLPs ensure overcoming the natural resistance of HIV-1 surface proteins associated with their low level of incorporation and inaccessibility of conserved epitopes to induce neutralizing antibodies. We also adopted this technology to modify Env trimers of the ZM53(T/F) strain to produce Env-VLPs by recombinant vaccinia viruses (rVVs). For VLP production, rVVs expressing Env, Gag-Pol (HIV-1/SIV), and the cowpox virus hr gene, which overcomes the restriction of vaccinia virus replication in CHO cells, were used. The CHO Lec1 engineered cell line lacking GlcNAc-TI was used for generating VLPs with Env proteins containing a cytoplasmic (CT) domain affecting the surface subunit (SU) conformation. This has created the opportunity to modulate the glycan composition, and refine the conditions for their production, and optimize approaches to overcoming HIV-1 resistance associated with abundant glycosylation.
引用
收藏
页码:763 / 772
页数:10
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