Serial analysis of gene expression in HIV‐1‐infected T cell lines

Abstract

The gene expression profile of the HIV-1 infection state was analyzed in the human T cell line MOLT-4. Using the serial analysis of gene expression (SAGE) method, a total of 142 603 SAGE tags were sequenced and identified, representing 43 581 unique mRNA species. Comparison of expression patterns revealed that 53 cellular genes were differentially expressed upon HIV-1 infection. Northern blot and RT-PCR analyses confirmed the altered expression of the genes in both MOLT-4 and MT-4 cells. Up-regulated genes were mainly composed of transcription factors and genes related to T cell activation, whereas downregulated genes were comprised of mitochondrial proteins, actinrelated factors and translational factors. These findings indicate that persistent T cell activation, which may accelerate HIV-1 replication, and the disruption of cellular housekeeping genes including those involved in anti-apoptotic systems, may play an important role in HIV-1-induced pathogenesis.z 1999 Federation of European Biochemical Societies.

Gene expression analysis of murine cells producing amphotropic mouse leukaemia virus at a cultivation temperature of 32 and 37 °C

“…Pietiäinen et al (2000) found that only in 20 % of the affected genes was gene expression downregulated (0?5 % downregulation and 2 % upregulation). However, our data do not reflect results found upon infection of cells with human immunodeficiency virus type 1 (HIV-1) (Ryo et al, 1999(Ryo et al, , 2000Geiss et al, 2000), where downregulated genes and upregulated genes were equal in number. This emphasizes that considerable differences exist in host-pathogen interactions upon lentivirus and oncoretrovirus infection.…”

“…Modification of the cytoskeleton as a result of virus infection has been described for several virus families (Cudmore et al, 1997;Ryo et al, 1999). Interaction with the cytoskeleton is important for certain steps in the life cycle of distinct viruses, for example, entry, budding and motility (Cudmore et al, 1997), and supports the efficient and directed transport of virus components to the places of virus replication, assembly and budding (Sodeik, 2000).…”

SOCS1 is an inducible host factor during HIV-1 infection and regulates the intracellular trafficking and stability of HIV-1 Gag

“…We and others have shown that HIV-1 infection can alter cellular gene expression patterns, resulting in the modification of viral replication and impaired homeostasis in the host cells (4,12). Hence, to elucidate further the genes and cellular pathways that participate in HIV-1 replication processes, we performed serial analysis of gene expression (SAGE) using either a HIV-1 or mock-infected human T cell line, .…”

Mitochondrial complex I activity is impaired during HIV-1-induced T-cell apoptosis

“…infected cells and comparing the global gene expression with uninfected controls using different techniques like differential display, serial analysis of gene expression, subtractive hybridization and microarray. [24][25][26][27][28] One of the studies using microarray, has clearly demonstrated marked changes in transcription of genes those may be essential for mitochondrial function and integrity, and DNA repair mechanisms directly leading to the induction of apoptosis. 27 Studies have also indicated a general decrease in majority of the metabolic enzymes upon HIV-1 infection.…”

“…28 HIV-1 infection has also been implicated to result in respiratory insufficiency and in general interference with oxidative metabolism, generating ROS and thus leading to apoptotic cell death. 25 Visualizing gene expression changes in purified population of cells is necessary to realize the subtle changes in gene expression modulated by HIV-1 and correlate induced changes with the observed phenotype. Based on differential gene expression analysis of isolated apoptotic cells, we report here specific downregulation of mitochondrial complex I subunit NDUFA6 with simultaneous impairment of complex I activity in HIV-induced T-cell apoptosis.…”