GLQ223: an inhibitor of human immunodeficiency virus replication in acutely and chronically infected cells of lymphocyte and mononuclear phagocyte lineage.
GLQ223 is a highly purified, formulated preparation of trichosanthin, a 26-kDa plant-derived ribosome-inactivating protein with potent inhibitory activity against human immunodeficiency virus (HIV) in vitro. The compound produced concentration-dependent inhibition of HIV replication in acutely infected cultures of T-lymphoblastoid cells (VB cell line). Treatment with GLQ223 selectively reduced levels of detectable viral proteins compared to total cellular protein synthesis and produced a selective decrease in levels of viral RNA relative to total cellular RNA in acutely infected cells. Substantial inhibition of viral replication was observed at concentrations of GLQ223 that showed little inhibition of parallel uninfected cultures. Selective anti-HIV activity was also observed in cultures of primary monocyte/macrophages chronically infected with HIV in vitro. When freshly drawn blood samples from HIV-infected patients were treated with a single 3-hr exposure to GLQ223. HIV replication was blocked for at least 5 days in subsequently cultured monocyte/macrophages, without further treatment. The anti-HIV activity of GLQ223 in both acutely and chronically infected cells and its activity in cells of both lymphoid and mononuclear phagocytic lineage make it an interesting candidate as a potential therapeutic agent in HIV infection and AIDS.
McGrath
M S
MS
Department of Medicine, University of California-San Francisco 94110.
Hwang
K M
KM
Caldwell
S E
SE
Gaston
I
I
Luk
K C
KC
Wu
P
P
Ng
V L
VL
Crowe
S
S
Daniels
J
J
Marsh
J
J
D000956:Antigens, Viral / Q000032:analysis; D000998:Antiviral Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D006678:HIV / Q000187:drug effects* / Q000254:growth & development; D006801:Humans; D066298:In Vitro Techniques; D008214:Lymphocytes / Q000382:microbiology; D008264:Macrophages / Q000382:microbiology; D009000:Monocytes / Q000382:microbiology; D010940:Plant Proteins / Q000494:pharmacology*; D012367:RNA, Viral / Q000378:metabolism; D015978:Trichosanthin; D014764:Viral Proteins / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects*
D000956:Antigens, Viral; D000998:Antiviral Agents; D010940:Plant Proteins; D012367:RNA, Viral; D014764:Viral Proteins; D015978:Trichosanthin