The 8 kD form encoded by the HTLV-1or F-1 is associated with low provirus levels and healthy carrier state in a subset of HTLV-1 infected individuals

• Autorzy: Bialuk I. , Walser J. , Fukumoto R. , Andresen V. , Graham J. , Jacobson S. , Gessain A. , Alcantara L. , Galvao-Castro B. , Franchini G.
• Języki publikacji: EN

Abstrakty

EN

HTLV-1 infection is linked with a neurodegenerative disorder HTLV1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). Expression of the singly or doubly spliced ORF-I cDNA of HTLV-1 results in the production of the 12 kD and 8 kD protein isoforms. The uncleaved 12 kD form resides in the ER and affects MHC-I and IL-2R. The cleaved 8 kD form traffi cs to the cell surface, is recruited to the immunological synapse upon T-Cell Receptor (TCR) stimulation decreasing TCR signaling and viral replication. Genetic analysis of ORF-I from ex vivo samples of HTLV-1 infected individuals reveals amino acid substitutions that affect its proteolytic cleavage, suggesting that ER or membrane associated functions of ORF-I may contribute to the persistence of HTLV-1 infected T-cells in the host. To investigate a putative relationship between ORF-I forms and provirus level, the best predictor of disease development, we measured the provirus level in the blood and linked it with the presence of ORF-I isoforms. The provirus levels ranged from 0.2 to 165 copies of proviral DNA per 106 PBMCs. DNA sequencing and reverse genetics revealed mutations at/in the vicinity of both cleavage sites within ORF-I. A rare mutation found at position 26 in ORF-I resulted mainly in the presence of the 8 kD isoform. Importantly, patients with this mutation had signifi cantly lower virus that those that carried either 12 kD isoform or both forms, and with one exception they belonged to a healthy carrier group.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2009
• Tom: 69
• Numer: 3
• Opis fizyczny: p.322

Twórcy

autor

Bialuk I.

• Animal Models and Retroviral Vaccines Section, National cancer Institute, Bethesda, USA
• Department of General and Experimental Pathology, Medical University of Bialystok, Bialystok, Poland

autor

Walser J.

• Section of Genomic Structure and Function, Laboratory of Molecular and Cellular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, USA

autor

Fukumoto R.

• Animal Models and Retroviral Vaccines Section, National Cancer Institute, Bethesda, USA

autor

Andresen V.

• Animal Models and Retroviral Vaccines Section, National Cancer Institute, Bethesda, USA

autor

Graham J.

• Viral Immunology Section, National Institute of Neurological Disorders and Stroke, Bethesda, USA

autor

Jacobson S.

• Viral Immunology Section, National Institute of Neurological Disorders and Stroke, Bethesda, USA

autor

Gessain A.

• Oncogenic Virus Epidemiology and Physiopathology Unit, department of Virology, Pasteur Institute, Paris, France

autor

Alcantara L.

• Oswaldo Cruz Foundation Salvador, Bahia, Brazil

autor

Galvao-Castro B.

• Oswaldo Cruz Foundation Salvador, Bahia, Brazil

autor

Franchini G.

• Animal Models and Retroviral Vaccines Section, National Cancer Institute, Bethesda, USA