CD4-Pseudomonas exotoxin conjugates delay but do not fully inhibit human immunodeficiency virus replication in lymphocytes in vitro.
The CD4 molecule is a high affinity receptor for the human immunodeficiency virus (HIV) envelope glycoprotein (gp160 or gp120). This glycoprotein is expressed on the surface membrane of cells infected with HIV. It has, therefore, been suggested that a soluble form of CD4 might be used as a targeting agent to deliver toxins selectively to cells infected with HIV. We demonstrate that CD4-Pseudomonas exotoxin A (PE) conjugates inhibit the proliferation of gp160-transfected Chinese hamster ovary cells and block HIV replication in virus-infected H9 cells. However, this inhibition of HIV replication appears to be incomplete since virus replication occurs following removal of the toxin conjugates from these cultures. Moreover, CD4-PE conjugates delay but do not inhibit HIV replication in human peripheral blood lymphocytes. These studies suggest that such conjugates should be assessed only as potential adjunctive therapies in the acquired immunodeficiency syndrome.
Tsubota
H
H
Harvard Medical School, New England Regional Primate Research Center, Southborough, Massachusetts 01772.
Winkler
G
G
Meade
H M
HM
Jakubowski
A
A
Thomas
D W
DW
Letvin
N L
NL
D036002:ADP Ribose Transferases; D000595:Amino Acid Sequence; D000818:Animals; D001427:Bacterial Toxins / Q000494:pharmacology*; D015704:CD4 Antigens; D002460:Cell Line; D006224:Cricetinae; D005098:Exotoxins / Q000494:pharmacology*; D006678:HIV / Q000502:physiology*; D000922:Immunotoxins / Q000494:pharmacology*; D008214:Lymphocytes / Q000382:microbiology*; D051379:Mice; D008969:Molecular Sequence Data; D013997:Time Factors; D037521:Virulence Factors; D014779:Virus Replication; D000097668:Pseudomonas aeruginosa Exotoxin A
D036002:ADP Ribose Transferases; D001427:Bacterial Toxins; D015704:CD4 Antigens; D005098:Exotoxins; D000922:Immunotoxins; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A