Modulation of Cellular Gene Expression by HIV Type 1 Infection as Determined by Subtractive Hybridization Cloning: Downregulation of Thymosin β₄ 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 genes whose expression is modulated by HIV-1 infection in the T leukemia cell line CEM. The gene encoding thymosin β₄, a ubiquitous polypeptide associated with hematopoietic differentiation, showed two- to threefold reduced transcription in HIV-1-infected CEM cells and other HIV-1-infected T cells and macrophages in vitro. Solid-phase radioimmunoassay revealed about a threefold decrease in the level of thymosin β₄ protein in lysates of infected cells. Northern blot analysis of RNA samples from lymphocytes of five AIDS patients reveals an up to fivefold reduction in the level of thymosin β₄ mRNA. These results indicate that HIV-1 infection may directly influence the expression of certain physiologically important proteins.