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The HIV-1 envelope glycoprotein that mediates fusion consists of the surface subunit gp120 which binds to cellular receptors (CD4, chemokine receptors) and the transmembrane subunit gp41. Infection by HIV-1 requires the fusogenic activity of gp41. The gp41 C-terminal heptad repeat (CHR) region interacts with the N-terminal heptad repeat (NHR) region to form a six-stranded core structure during the conformational change of gp41 that is crucial for HIV-1 membrane fusion.1-2) Therefore, we designed gp160 mutant plasmids which had mutation
sites on N:C contact amino acid points on which HIV-1 gp41 NHR and CHR regions were combined together. 293T cells were transfected with these plasmids and were co-cultured with HeLa-TZM cells to measure fusion activity change by gp41 mutation. Also, we produced lentiviruses which had HIV-1 gp160 mutant glycoprotein and expressed green fluorescence protein (GFP). HeLa-TZM cells were infected with these viruses and virus titers were measured. As a result, most single or double mutants showed very low fusion activity. However,
particular mutants (V570I:I635V and V570I) showed significantly increased fusion activity. In conclusion, N:C contact amino acid points of gp41 should be structurally stable to infect target cells. Our mutants may give partial information on the efficiencies of HIV-1 protein or vectored vaccines.