title: Inhibition of HIV type 1 infectivity by coexpression of a wild-type and a defective glycoprotein 120.
abstract: An amino acid substitution (D --> K) in the C3 region of HIV-1 gp120 has previously been shown to inhibit binding of virions to CD4+ cells. We have introduced the same mutation into the HIV-1 isolate LAV-I(BRU), in which the mutation is denoted D373K. Here we show that the D373K envelope protein is processed and incorporated into virus particles, but that D373K virions have no detectable infectivity (below 0.1% relative to wild type). When D373K and the wild-type envelope gene were cotransfected in 293 cells at a 4:1 ratio, the resultant infectivity of the HIV-1 supernatant was reduced more than 100-fold. When the same ratio of plasmids was tested in COS-1 cells the inhibition of HIV-1 was an order of magnitude less than observed in 293 cells. COS-1 and 293 cells differed in that only 293 cells displayed saturation of virus production with respect to the envelope protein. Our data fit a simple model: when virion formation is saturated with envelope protein, expression and incorporation of a defective envelope protein imply a corresponding dilution of wild-type protein on the surface of virions. The cooperative function of wild-type envelope proteins is subsequently compromised, and a trans-dominant inhibition of virus infectivity is observed.
authors.affiliation: Laboratory for Infectious Diseases, Department 144, Hvidovre Hospital, Denmark.
authors.forename: O S
authors.initials: OS
authors.lastname: Lund
authors.forename: B
authors.initials: B
authors.lastname: Losman
authors.forename: K
authors.initials: K
authors.lastname: Schønning
authors.forename: A
authors.initials: A
authors.lastname: Bolmstedt
authors.forename: S
authors.initials: S
authors.lastname: Olofsson
authors.forename: J E
authors.initials: JE
authors.lastname: Hansen
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D019556:COS Cells; D002461:Cell Line, Transformed; D015699:HIV Envelope Protein gp120 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D016297:Mutagenesis, Site-Directed; D014779:Virus Replication / Q000235:genetics
chemical_list: D015699:HIV Envelope Protein gp120