Continuous presence of CD4-PE40 is required for antiviral activity against single-passage HIV isolates and infected peripheral blood mononuclear cells.
CD4-PE40, a recombinant protein consisting of a portion of human CD4 linked to Pseudomonas aeruginosa exotoxin, was studied in vitro to assess its ability to inhibit the replication of primary isolates of HIV. CD4-PE40 was added to cultures of phytohemagglutin (PHA)-stimulated normal peripheral blood mononuclear cells (PBMCs) infected either with the laboratory strain HIVIIIb or single-passage virus stocks derived from patient PBMCs. Results showed that the replication of HIVIIIb was inhibited by a single pulse of CD4-PE40 and, more significantly, by continuous exposure to the drug. The replication of primary virus isolates, however, was inhibited only by continuous exposure to CD4-PE40. Cultures of freshly isolated PBMCs from HIV-seropositive individuals that were directly treated with CD4-PE40 before culture also required the continuous presence of drug to demonstrate inhibition of HIV replication. These results suggest that continuous administration of CD4-PE40 may be required to produce a significant anti-HIV effect in vivo.
Winters
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MA
Center for AIDS Research, Stanford University Medical Center, California 94305.
Merigan
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TC
D000998:Antiviral Agents / Q000494:pharmacology*; D005098:Exotoxins / Q000494:pharmacology*; D016655:HIV Core Protein p24 / Q000096:biosynthesis; D015699:HIV Envelope Protein gp120 / Q000378:metabolism; D015658:HIV Infections / Q000188:drug therapy / Q000382:microbiology; D015497:HIV-1 / Q000187:drug effects* / Q000302:isolation & purification / Q000502:physiology; D006801:Humans; D000922:Immunotoxins / Q000494:pharmacology*; D066298:In Vitro Techniques; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000382:microbiology; D011994:Recombinant Proteins / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; C057689:CD4-Pseudomonas toxin; D005098:Exotoxins; D016655:HIV Core Protein p24; D015699:HIV Envelope Protein gp120; D000922:Immunotoxins; D011994:Recombinant Proteins