HIV-1 SUPPRESSES ERYTHROPOIETIN PRODUCTION IN-VITRO

Serum erythropoietin (Epo) levels are depressed in anemic AIDS patient s relative to controls. The basis for abnormal regulation of Epo has n ot been defined. The hepatoma cell line Hep3B produces Epo in response to hypoxia and serves as a model for the study of Epo regulation. Hep 3B cells are infectible with human immunodeficiency virus-1 (HIV-1) an d were used as a model for evaluating potential direct effects of HIV on Epo expression. HIV-1 infected or transfected Hep3B cells produced Epo at significantly lower levels than uninfected Hep3B cells under lo w O-2 conditions or following exposure to cobalt chloride. Epo product ion induced by hypoxia of HIV-1 infected Hep3B cells was depressed com pared with non-HIV containing Hep3B cells when normalized for cell num ber, total cellular protein or albumin, but not depressed when normali zed for alpha-fetoprotein production. The cellular levels of Epo mRNA were not diminished in the HIV-1(+) Hep3B cells, indicating a probable posttranscriptional effect of HIV-1 on Epo production. Cellular prote in production or secretion rates as measured by precipitable H-3-leuci ne were not affected by the presence of HIV-1. HIV-1 appeared to depre ss the production of Epo and some, but not all, other cellular protein s. These results suggest that impaired production of Epo may be a dire ct effect of HIV-1 infection possibly contributing to anemia in AIDS.