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Human T-lymphotropic virus type 1 mitochondrion-localizing protein p13(II) is required for viral infectivity in vivo.
- Source :
-
Journal of virology [J Virol] 2006 Apr; Vol. 80 (7), pp. 3469-76. - Publication Year :
- 2006
-
Abstract
- Human T-lymphotropic virus type 1 (HTLV-1), the etiological agent of adult T-cell leukemia, encodes unique regulatory and accessory proteins in the pX region of the provirus, including the open reading frame II product p13(II). p13(II) localizes to mitochondria, binds farnesyl pyrophosphate synthetase, an enzyme involved in posttranslational farnesylation of Ras, and alters Ras-dependent cell signaling and control of apoptosis. The role of p13(II) in virus infection in vivo remains undetermined. Herein, we analyzed the functional significance of p13(II) in HTLV-1 infection. We compared the infectivity of a human B-cell line that harbors an infectious molecular clone of HTLV-1 with a selective mutation that prevents the translation of p13(II) (729.ACH.p13) to the infectivity of a wild-type HTLV-1-expressing cell line (729.ACH). 729.ACH and 729.ACH.p13 producer lines had comparable infectivities for cultured rabbit peripheral blood mononuclear cells (PBMC), and the fidelity of the start codon mutation in ACH.p13 was maintained after PBMC passage. In contrast, zero of six rabbits inoculated with 729.ACH.p13 cells failed to establish viral infection, whereas six of six rabbits inoculated with wild-type HTLV-1-expressing cells (729.ACH) were infected as measured by antibody responses, proviral load, and HTLV-1 p19 matrix antigen production from ex vivo-cultured PBMC. Our data are the first to indicate that the HTLV-1 mitochondrion-localizing protein p13(II) has an essential biological role during the early phase of virus infection in vivo.
- Subjects :
- Animals
Antibodies, Viral metabolism
Blotting, Western
Cell Line, Tumor
Cells, Cultured
Coculture Techniques
Codon, Initiator
Disease Models, Animal
Enzyme-Linked Immunosorbent Assay
Female
Gene Products, gag blood
Genome, Viral
Human T-lymphotropic virus 1 genetics
Human T-lymphotropic virus 1 immunology
Human T-lymphotropic virus 1 pathogenicity
Humans
Leukocytes, Mononuclear virology
Mutation
Polymerase Chain Reaction
Proviruses genetics
Proviruses isolation & purification
Rabbits
Retroviridae Proteins, Oncogenic blood
Viral Load
gag Gene Products, Human Immunodeficiency Virus
Geranyltranstransferase physiology
HTLV-I Infections virology
Human T-lymphotropic virus 1 physiology
Mitochondria enzymology
Subjects
Details
- Language :
- English
- ISSN :
- 0022-538X
- Volume :
- 80
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Journal of virology
- Publication Type :
- Academic Journal
- Accession number :
- 16537614
- Full Text :
- https://doi.org/10.1128/JVI.80.7.3469-3476.2006