HTLV1 Mutation Detail Information

Virus Mutation HTLV1 Mutation L319R


Basic Characteristics of Mutations
Mutation Site L319R
Mutation Site Sentence The diagram in Fig. 1B shows the sites of amino acid substitution mutations within Tax that impair CREB/ATF-dependent (M47: L319R; L320R; Smith and Greene, 1990) or NF-κB-dependent (M22: T130A; L131S; Smith and Greene, 1990, and G148V; Yamaoka et al., 1996) transactivation.
Mutation Level Amino acid level
Mutation Type Nonsynonymous substitution
Gene/Protein/Region tax
Standardized Encoding Gene tax  
Genotype/Subtype -
Viral Reference -
Functional Impact and Mechanisms
Disease Cell line    
Immune -
Target Gene -
Clinical and Epidemiological Correlations
Clinical Information -
Treatment -
Location -
Literature Information
PMID 31299491
Title The human T-cell leukemia virus type-1 tax oncoprotein dissociates NF-kappaB p65(RelA)-Stathmin complexes and causes catastrophic mitotic spindle damage and genomic instability
Author Malu A,Hutchison T,Yapindi L,Smith K,Nelson K,Bergeson R,Pope J,Romeo M,Harrod C,Ratner L,Van Lint C,Harrod R
Journal Virology
Journal Info 2019 Sep;535:83-101
Abstract Genomic instability is a hallmark of many cancers; however, the molecular etiology of chromosomal dysregulation is not well understood. The human T-cell leukemia virus type-1 (HTLV-1) oncoprotein Tax activates NF-kappaB-signaling and induces DNA-damage and aberrant chromosomal segregation through diverse mechanisms which contribute to viral carcinogenesis. Intriguingly, Stathmin/oncoprotein-18 (Op-18) depolymerizes tubulin and interacts with the p65(RelA) subunit and functions as a cofactor for NF-kappaB-dependent transactivation. We thus hypothesized that the dissociation of p65(RelA)-Stathmin/Op-18 complexes by Tax could lead to the catastrophic destabilization of microtubule (MT) spindle fibers during mitosis and provide a novel mechanistic link between NF-kappaB-signaling and genomic instability. Here we report that the inhibition of Stathmin expression by the retroviral latency protein, p30(II), or knockdown with siRNA-stathmin, dampens Tax-mediated NF-kappaB transactivation and counters Tax-induced genomic instability and cytotoxicity. The Tax-G148V mutant, defective for NF-kappaB activation, exhibited reduced p65(RelA)-Stathmin binding and diminished genomic instability and cytotoxicity. Dominant-negative inhibitors of NF-kappaB also prevented Tax-induced multinucleation and apoptosis. Moreover, cell clones containing the infectious HTLV-1 ACH. p30(II) mutant provirus, impaired for p30(II) production, exhibited increased multinucleation and the accumulation of cytoplasmic tubulin aggregates following nocodozole-treatment. These findings allude to a mechanism whereby NF-kappaB-signaling regulates tubulin dynamics and mitotic instability through the modulation of p65(RelA)-Stathmin/Op-18 interactions, and support the notion that p30(II) enhances the survival of Tax-expressing HTLV-1-transformed cells.
Sequence Data -
Mutation Information
Note
Basic Characteristics of Mutations
  • Mutation Site: The specific location in a gene or protein sequence where a change occurs.
  • Mutation Level: The level at which a mutation occurs, including the nucleotide or amino acid level.
  • Mutation Type: The nature of the mutation, such as missense mutation, nonsense mutation, synonymous mutation, etc.
  • Gene/Protein/Region: Refers to the specific region of the virus where the mutation occurs. Including viral genes, viral proteins, or a specific viral genome region. If the article does not specifically indicate the relationship between the mutation and its correspondence, the main
  • Gene/Protein/Region studied in the article is marked.
  • Genotype/Subtype: Refers to the viral genotype or subtype where the mutation occurs. If the article does not specifically indicate the relationship between the mutation and its correspondence, the main Genotype/Subtype studied in the article is marked.
  • Viral Reference: Refers to the standard virus strain used to compare and analyze viral sequences.
Functional Impact and Mechanisms
  • Disease: An abnormal physiological state with specific symptoms and signs caused by viral infection.
  • Immune: The article focuses on the study of mutations and immune.
  • Target Gene: Host genes that viral mutations may affect.
Clinical and Epidemiological Correlations
  • Clinical Information: The study is a clinical or epidemiological study and provides basic information about the population.
  • Treatment: The study mentioned a certain treatment method, such as drug resistance caused by mutations. If the study does not specifically indicate the relationship between mutations and their correspondence treatment, the main treatment studied in the article is marked.
  • Location: The source of the research data.
Literature Information
  • Sequence Data: The study provides the data accession number.