Inhibition of HIV type 1 infectivity by coexpression of a wild-type and a defective glycoprotein 120.
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Inhibition of HIV type 1 infectivity by coexpression of a wild-type and a defective glycoprotein 120. / Lund, O S; Losman, B; Schønning, Kristian; Bolmstedt, A; Olofsson, S; Hansen, J E.
I: AIDS Research and Human Retroviruses, Bind 14, Nr. 16, 1998, s. 1445-1450.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning
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T1 - Inhibition of HIV type 1 infectivity by coexpression of a wild-type and a defective glycoprotein 120.
AU - Lund, O S
AU - Losman, B
AU - Schønning, Kristian
AU - Bolmstedt, A
AU - Olofsson, S
AU - Hansen, J E
PY - 1998
Y1 - 1998
N2 - 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.
AB - 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.
M3 - Journal article
VL - 14
SP - 1445
EP - 1450
JO - AIDS Research and Human Retroviruses
JF - AIDS Research and Human Retroviruses
SN - 0889-2229
IS - 16
ER -
ID: 34064906