Back to Search
Start Over
Surface Stability and Immunogenicity of the Human Immunodeficiency Virus Envelope Glycoprotein: Role of the Cytoplasmic Domain
- Publication Year :
- 2004
- Publisher :
- American Society for Microbiology, 2004.
-
Abstract
- The effects of two functional domains, the membrane-proximal YXXΦ motif and the membrane-distal inhibitory sequence in the long cytoplasmic tail of the human immunodeficiency virus type 1 (HIV-1) envelope protein (Env), on immunogenicity of the envelope protein were investigated. Genes with codons optimized for mammalian expression were synthesized for the HIV 89.6 Env and a truncated Env with 50 amino acids in the cytoplasmic domain to delete the membrane distal inhibitory sequence for surface expression. Additional genes were generated in which the tyrosine residue in the YXXΦ motif was changed into a serine. Pulse-chase radioactive labeling and immunoprecipitation studies indicated that both domains can mediate endocytosis of the HIV Env, and removal of both domains is required to enhance HIV Env protein surface stability. Analysis of immune responses induced by DNA immunization of mice showed that the DNA construct for the mutant Env exhibiting enhanced surface stability induced significantly higher levels of antibody responses against the HIV Env protein. Our results suggest that the HIV Env cytoplasmic domain may play important roles in virus infection and pathogenesis by modulating its immunogenicity.
- Subjects :
- Gene Expression Regulation, Viral
Cytoplasm
Immunoprecipitation
viruses
Immunology
Amino Acid Motifs
Biology
CD8-Positive T-Lymphocytes
HIV Antibodies
Microbiology
Virus
Mice
Viral envelope
Virology
Vaccines and Antiviral Agents
Animals
Humans
Tyrosine
Gene
chemistry.chemical_classification
Mice, Inbred BALB C
Immunogenicity
virus diseases
Gene Products, env
Endocytosis
chemistry
Insect Science
DNA, Viral
Mutation
HIV-1
DNA construct
Female
Immunization
Glycoprotein
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....c4dae6ca20ae3567bb03be62e1082db8