A trans-dominant mutation in human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein gp41 inhibits membrane fusion when expressed in target cells.
A recombinant vaccinia virus was used to express a mutation in the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein gp120-gp41. In this mutant protein, the second amino acid in the N-terminal region of gp41 has been converted from a hydrophobic valine residue to the polar glutamate. When recombinant vaccinia viruses encoding wild-type HIV-1 envelope glycoprotein infect a lymphocyte cell line lacking CD4, the cells express the HIV-1 envelope glycoprotein gp120-gp41 and are able to fuse with a CD4(4) T lymphocyte cell line. Cells expressing the mutant envelope glycoprotein are unable to fuse with CD4(4) T lymphocytes. When both viruses infect CD4- cells simultaneously, there is an inhibition of fusion to CD4+ cells with an increasing fraction of the virus encoding the mutated envelope glycoprotein. Interestingly, when the opposing, or CD4+ target cells are infected with the mutation-expressing virus, while CD4- cells are infected with wild-type envelope-expressing virus, a similar inhibition of fusion is observed. This suggests that the mutated envelope glycoprotein does not need to reside in the same membrane as the wild-type protein it inhibits.
Elson
H F
HF
Section on Membrane Structure and Function, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Dimitrov
D S
DS
Blumenthal
R
R
D000911:Antibodies, Monoclonal; D001483:Base Sequence; D015704:CD4 Antigens / Q000276:immunology / Q000378:metabolism; D015967:Gene Expression Regulation, Viral; D005822:Genetic Vectors; D015700:HIV Envelope Protein gp41 / Q000235:genetics* / Q000494:pharmacology*; D015497:HIV-1 / Q000737:chemistry* / Q000235:genetics*; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism / Q000821:virology; D008561:Membrane Fusion / Q000187:drug effects*; D008969:Molecular Sequence Data; D009154:Mutation; D010957:Plasmids / Q000235:genetics; D011995:Recombination, Genetic; D014616:Vaccinia virus / Q000235:genetics / Q000378:metabolism
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D015700:HIV Envelope Protein gp41