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Basic Characteristics of Mutations
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Mutation Site
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N195D |
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Mutation Site Sentence
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Furthermore, a single amino acid substitution, N195D, in HTLV-1 SU (Ach.195) resulted in a shift to a CD8+ T cell immortalization tropism preference. Longitudinal phenotyping analyses of the in vitro transformation process revealed that CD4+ T cells emerged as the predominant population by week 5 in wtHTLV-1 cultures, while CD8+ T cells emerged as the predominant population by weeks 4 and 7 in wtHTLV-2 and Ach.195 cultures, respectively. |
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Mutation Level
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Amino acid level |
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Mutation Type
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Nonsynonymous substitution |
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Gene/Protein/Region
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env |
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Standardized Encoding Gene
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env
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Genotype/Subtype
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- |
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Viral Reference
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-
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Functional Impact and Mechanisms
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Disease
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Cell line
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Immune
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- |
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Target Gene
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-
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Clinical and Epidemiological Correlations
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Clinical Information
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- |
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Treatment
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- |
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Location
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- |
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Literature Information
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PMID
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23785214
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Title
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Human T lymphotropic virus type 1 SU residue 195 plays a role in determining the preferential CD4+ T cell immortalization/transformation tropism
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Author
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Kannian P,Fernandez S,Jones KS,Green PL
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Journal
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Journal of virology
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Journal Info
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2013 Aug;87(16):9344-52
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Abstract
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Human T lymphotropic virus type 1 (HTLV-1) mainly causes adult T cell leukemia and predominantly immortalizes/transforms CD4(+) T cells in culture. HTLV-2 is aleukemic and predominantly immortalizes/transforms CD8(+) T cells in culture. We have shown previously that the viral envelope is the genetic determinant of the differential T cell tropism in culture. The surface component (SU) of the HTLV-1 envelope is responsible for binding to the cellular receptors for entry. Here, we dissect the HTLV-1 SU further to identify key domains that are involved in determining the immortalization tropism. We generated HTLV-1 envelope recombinant virus containing the HTLV-2 SU domain. HTLV-1/SU2 was capable of infecting and immortalizing freshly isolated peripheral blood mononuclear cells in culture. HTLV-1/SU2 shifted the CD4(+) T cell immortalization tropism of wild-type HTLV-1 (wtHTLV-1) to a CD8(+) T cell preference. Furthermore, a single amino acid substitution, N195D, in HTLV-1 SU (Ach.195) resulted in a shift to a CD8(+) T cell immortalization tropism preference. Longitudinal phenotyping analyses of the in vitro transformation process revealed that CD4(+) T cells emerged as the predominant population by week 5 in wtHTLV-1 cultures, while CD8(+) T cells emerged as the predominant population by weeks 4 and 7 in wtHTLV-2 and Ach.195 cultures, respectively. Our results indicate that SU domain independently influences the preferential T cell immortalization tropism irrespective of the envelope counterpart transmembrane (TM) domain. We further showed that asparagine at position 195 in HTLV-1 SU is involved in determining this CD4(+) T cell immortalization tropism. The slower emergence of the CD8(+) T cell predominance in Ach.195-infected cultures suggests that other residues/domains contribute to this tropism preference.
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Sequence Data
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-
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