MODULATION OF CELLULAR GENE-EXPRESSION BY HIV TYPE-1 INFECTION AS DETERMINED BY SUBTRACTIVE HYBRIDIZATION CLONING - DOWN-REGULATION OF THYMOSIN BETA(4) IN-VITRO AND IN-VIVO

Chronic infection with HIV-1 has profound effects on host cell growth and function. We used subtractive hybridization cloning to identify ge nes whose expression is modulated by HIV-1 infection in the T leukemia cell line CEM. The gene encoding thymosin beta(4), a ubiquitous polyp eptide associated with hematopoietic differentiation, showed two- to t hreefold reduced transcription in HIV-1-infected CEM cells and other H IV-1-infected T cells and macrophages in vitro. Solid-phase radioimmun oassay revealed about a threefold decrease in the level of thymosin be ta(4) protein in lysates of infected cells. Northern blot analysis of RNA samples from lymphocytes of five AIDS patients reveals an up to fi vefold reduction in the level of thymosin beta(4) mRNA. These results indicate that HIV-1 infection may directly influence the expression of certain physiologically important proteins.