The interleukin-2 fusion protein, DAB389IL-2, inhibits the development of infectious virus in human immunodeficiency virus type 1-infected human peripheral blood mononuclear cells.
DAB389IL-2 is a genetically engineered fusion protein that reduces human immunodeficiency virus type 1 (HIV-1) replication in activated, interleukin (IL)-2 receptor (IL-2R)-expressing human peripheral blood mononuclear cells (PBMC). The level of infectious virus released by cultured PBMC after treatment with DAB389IL-2 was measured by a quantitative microculture assay. The inhibition of p24 antigen production was also evaluated in cultures that differed in duration of infection and activation state. Although the activation state of the cell and the time of DAB389IL-2 addition to the cultures influenced its anti-HIV activity, DAB389IL-2 treatment decreased levels of infectious HIV-1 to 0.1%-6.5% of untreated cell levels. DAB389IL-2 also decreased p24 antigen expression to 10%-48% of controls, even when added as late as 8 days after acute infection. Mutational variants of DAB389IL-2 that lack catalytic activity or IL-2R binding are without anti-HIV activity.
Zhang
L J
LJ
Division of Infectious Diseases, Beth Israel Hospital, Boston, Massachusetts 02215, USA.
Waters
C A
CA
Poisson
L R
LR
Estis
L F
LF
Crumpacker
C S
CS
D019380:Anti-HIV Agents / Q000494:pharmacology*; D004167:Diphtheria Toxin / Q000494:pharmacology*; D016655:HIV Core Protein p24 / Q000096:biosynthesis; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000821:virology*; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000494:pharmacology
D019380:Anti-HIV Agents; D004167:Diphtheria Toxin; D016655:HIV Core Protein p24; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D011993:Recombinant Fusion Proteins; C078456:denileukin diftitox