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PMID: 10364321 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Both neutralization resistance and high infectivity phenotypes are caused by mutations of interacting residues in the human immunodeficiency virus type 1 gp41 leucine zipper and the gp120 receptor- and coreceptor-binding domains.

Journal of virology ·Vol. 73 ·No. 7 ·1999-07-00 ·Pages 5707-13

Park EJ, Quinnan GV

Abstract

Neutralization resistance of human immunodeficiency virus type 1 (HIV-1) is a major impediment to vaccine development. We have found that residues of HIV-1 MN strain in the C terminus of gp120 and the leucine zipper (LZ) region of gp41 viral envelope proteins interact cooperatively to determine neutralization resistance and modulate infectivity. Further, results demonstrate that this interaction, by which regions of gp120 are assembled onto the LZ, involves amino acid residues intimately related to those which participate in the binding of the envelope to its receptor and coreceptor. Variations in this critical assembly structure determine the concordant, interdependent evolution of increased infectivity efficiency and neutralization resistance phenotypes of the envelopes. The results elucidate important structure-function relationships among epitopes that are important targets of vaccine development.

MeSH Terms
Binding Sites CD4 Antigens/metabolism HIV Envelope Protein gp120/genetics,immunology,metabolism HIV Envelope Protein gp41/genetics,immunology,metabolism HIV-1/genetics,immunology,physiology Humans Leucine Zippers/genetics,immunology Mutagenesis, Site-Directed Neutralization Tests Phenotype Receptors, CXCR4/metabolism
Chemicals
CD4 Antigens HIV Envelope Protein gp120 HIV Envelope Protein gp41 Receptors, CXCR4
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Park E J
Department of Preventive Medicine and Biometrics, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814, USA.
Quinnan G V
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.73.7.5707-5713.1999
Published
1999-07-00
Pages
5707-13
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC112630
Subset
IM
Grants
NIAID NIH HHS · R01 AI037438 · United States
NIAID NIH HHS · R01-AI37438 · United States
External Links
PubMed source DOI: 10.1128/JVI.73.7.5707-5713.1999 PMC Full Text View journal details
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