title: Analysis of dominant-negative effects of mutant Env proteins of human immunodeficiency virus type 1.
abstract: The Env protein of human immunodeficiency virus type 1 is assembled into a stable trimer, and oligomerization is required for maintenance of viral infectivity. This property of Env suggests that Env mutants may have a dominant-negative effect on virus infectivity. To investigate this possibility, we established a packaging cell line in which both wild-type and mutant Env proteins could be expressed simultaneously in a single cell. We analyzed the effects of two types of Env mutants: cytoplasmic tail-truncated TM mutants and a mutant defective in gp120/gp41 cleavage. The cytoplasmic tail-truncated proteins were found to be incorporated into virions by forming an oligomer with wild-type TM, but could not inhibit the wild-type function. In contrast, phenotypic mixing of cleavage-defective Env with the wild-type protein caused dramatic inhibition of infectivity, indicating that this mutant has a strong dominant-negative phenotype.
authors.affiliation: Department of Microbiology, Yamanashi Medical University, Tamaho-cho, Yamanashi, 409-3898, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Iwatani
authors.forename: K
authors.initials: K
authors.lastname: Kawano
authors.forename: T
authors.initials: T
authors.lastname: Ueno
authors.forename: M
authors.initials: M
authors.lastname: Tanaka
authors.forename: A
authors.initials: A
authors.lastname: Ishimoto
authors.forename: M
authors.initials: M
authors.lastname: Ito
authors.forename: H
authors.initials: H
authors.lastname: Sakai
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000821:virology*; D015967:Gene Expression Regulation, Viral; D015699:HIV Envelope Protein gp120 / Q000235:genetics*; D015700:HIV Envelope Protein gp41 / Q000235:genetics*; D015497:HIV-1 / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D009154:Mutation; D014779:Virus Replication / Q000235:genetics
chemical_list: D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41