Mechanism of the gene expression of HTLV-I and its association with ATL.
Human T-cell leukemia virus type 1 (HTLV-1) is the etiologic agent of adult T-cell leukemia (ATL) and a trans-acting viral function was proposed to be involved in ATL development because of the non-specific provirus integration in leukemic cells and the frequent immortalization of helper T-cells by in vitro infection. An extra sequence "pX" in the HTLV-1 genome codes for three proteins, p40x-, p27x- and p21x-, and the p40x- is trans-activator of transcription from the viral LTR. A sequence of 21 bp repeats in the LTR was found to be an enhancer and respond to the trans-activation by p40x-. The transient expression of p40x- also activates a cellular gene for interleukin 2 receptor (IL-2R) in helper T-cell lines. This induction of IL-2R may explain the mechanism of preferential growth of HTLV-1 infected cells and may be an early event of ATL development. For practical purposes, the env gene fragments was expressed in E. coli as fusion proteins with beta-galactosidase. Using these fusion proteins, a diagnostic system detecting anti-env antibodies was developed. Immunization of monkeys with these envelope-fusion proteins protected the monkeys from the viral infection, suggesting possible usage of envelope proteins as vaccine.
D000818:Animals; D002472:Cell Transformation, Viral; D017977:Deltaretrovirus / Q000235:genetics* / Q000472:pathogenicity; D005786:Gene Expression Regulation; D005796:Genes; D005814:Genes, Viral; D000882:Haplorhini; D006801:Humans; D007938:Leukemia / Q000209:etiology*; D011817:Rabbits; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000235:genetics; D015375:Receptors, Interleukin-2; D011993:Recombinant Fusion Proteins / Q000276:immunology; D012091:Repetitive Sequences, Nucleic Acid; D012191:Retroviridae Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D013601:T-Lymphocytes; D015534:Trans-Activators; D014158:Transcription, Genetic; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology / Q000302:isolation & purification
D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D011993:Recombinant Fusion Proteins; D012191:Retroviridae Proteins; D015534:Trans-Activators; D014759:Viral Envelope Proteins; D014765:Viral Vaccines