Disease relevance of Human T-lymphotropic virus 2

• A sensitive modification of the polymerase chain reaction method was used to provide unambiguous molecular evidence that a significant proportion of intravenous drug abusers are infected with HTLV, and the majority of these individuals are infected with HTLV-II rather than HTLV-I [1].
• These women had a syndrome similar to the olivopontocerebellar atrophy variant of multiple system atrophy, and HTLV-II infection was confirmed by western blot and the polymerase chain reaction [2].
• To evaluate the reciprocal influence of HTLV-II and HIV-1 infection, primary peripheral blood mononuclear cell (PBMC) cultures from coinfected individuals were established in the presence of interleukin 2 (IL-2) [3].
• In the present study, we describe a case of chronic T-lymphocytic leukemia (T-CLL) with monoclonal proliferation of human T-lymphotropic retrovirus (HTLV)-I or HTLV-II negative CD3(+)4(+)8(-) T cell expressing IL-2 receptors without stimulation [4].
• The recent report that arsenic trioxide induces apoptosis in HTLV-1-transformed cells prompted investigation of the mechanism of action of this drug in HTLV-1 and HTLV-2 interleukin-2-independent T cells and in HTLV-1-immortalized cells or in ex vivo ATLL samples [5].

High impact information on Human T-lymphotropic virus 2

• Of 23 individuals confirmed by polymerase chain reaction analysis to be infected with HTLV, 21 were identified to be infected with HTLV-II, and 2 were infected with HTLV-I [1].
• It is demonstrated here that introduction of the trans-activator (tat) gene of HTLV-II into the Jurkat T-lymphoid cell line results in the induction of both interleukin-2 receptor and interleukin-2 gene expression [6].
• It is encoded by sequences containing the env initiation codon and one nucleotide of the next codon spliced to the major open reading frame of the HTLV-I and HTLV-II x gene [7].
• RP-IIB, which contains aminoacids 96-235 from HTLV-II exterior glycoprotein gp52, was reactive with all HTLV-II samples [8].
• HTLV-II CM was highly angiogenic in vivo, which was blocked by antibodies against SF [9].

Chemical compound and disease context of Human T-lymphotropic virus 2

• HTLV-II proviral levels in the peripheral blood remained relatively constant, despite therapy with zidovudine [10].
• Our results indicate that p24rex of HTLV-II is not initiated at an internal AUG and that the internal methionine codons are not crucial to the function of the rex gene and, ultimately, the transforming properties of the virus [11].
• To determine whether HTLV-II infection is associated with impaired humoral immune responses, we immunized a cohort of HTLV-II-infected subjects and matched uninfected control subjects with 23-valent pneumococcal polysaccharide and tetanus toxoid vaccines [12].
• To identify risk factors for human T lymphotropic virus type II (HTLV-II) infection in intravenous drug users (IVDUs), participants in a longitudinal study of human immunodeficiency virus (HIV) infection in a New York methadone maintenance program were studied [13].
• These results suggest that the spontaneous proliferation in HTLV-II asymptomatic carriers is due to expansion of CD8 cells expressing integrin receptors which may serve as costimulatory molecules for their activation [14].

Biological context of Human T-lymphotropic virus 2

• The HTLV-II primer-amplified polymerase chain reaction products from two of these subjects were partially sequenced and matched published HTLV-II nucleotide sequences in both p24 gag (94% of 107 bases) and pol (98% of 112 bases) regions [15].
• This effect results from CIITA inhibiting the Tax-mediated transactivation of the HTLV-2 long-term repeat [16].
• In all gene regions analyzed, this strain was the most divergent HTLV-2 strain, differing by 2.4% (tax/rex) to 10.7% (long terminal repeat) from both subtypes HTLV-2a and HTLV-2b, yet major functional elements are conserved [17].
• In contrast, HTLV-2 Tax (Tax2) did not detectably alter p21 or p27 gene expression, failed to induce cell cycle arrest, failed to suppress hematopoiesis in CD34(+) cells, and did not protect cells from programmed cell death [18].
• A novel monoclonal antibody (MAb), N5.4.4, specifically reactive with human T-lymphotropic virus type-II (HTLV-II) envelope glycoprotein (gp) has been developed through immunization with a synthetic peptide corresponding to the amino acid sequence 171-196 of the HTLV-II envelope protein (II-env 171-196) [19].

Anatomical context of Human T-lymphotropic virus 2

• Rat lymphoid cell lines producing human T cell leukemia virus. II. Constitutive expression of rat interleukin 2 receptor [20].
• Synthetic peptides of 20-25 amino acids were employed in enzyme-linked immunosorbent assays to identify linear epitopes in the external glycoprotein gp46 and the transmembrane glycoprotein gp21 of human T-cell leukemia/lymphotropic viruses type I (HTLV-I) and II (HTLV-II) [21].
• In a cotransfection assay, the Tax protein of both HTLV-I and HTLV-II specifically activated transcription from the IL-1alpha promoter in an uninfected Jurkat cell line [22].
• Thus, these studies indicate a role for a 78- to 80-kDa glycoprotein in HTLV-I or HTLV-II infection and syncytium formation [23].
• We observed expression of envelope gp46 protein on an HTLV-II-producing T-cell line (Mo) cells by an immunoelectron microscopical method using a monoclonal antibody against HTLV-II gp46. gp46 reactivity was observed on virus-like particles, extracellular vesicles, cell membrane, and partially in nuclear membrane and endoplasmic reticulum [24].

Gene context of Human T-lymphotropic virus 2

• The MHC class II transcriptional activator (CIITA) inhibits HTLV-2 viral replication by blocking the function of the viral transactivator Tax-2 [16].
• Further, there was a direct correlation between the spontaneous proliferation of lymphocytes from patients infected with HTLV-II and expression of CD80, which could be blocked by simultaneous addition of anti-CD80 and anti-CD86 [25].
• Our findings indicate that both HTLV-2 and HIV-1 infection prime T lymphocytes for STAT1 activation, but they also highlight an interference exerted by HTLV-2 on HIV-1-induced STAT1 activation [26].
• Thus, the shift in the suppressor/cytotoxic to helper/inducer 'memory' CD4+ may be associated with immunoregulatory abnormalities often found in persons infected with HTLV-I or HTLV-II [27].
• Northern blot analysis of T-cell lines generated from individuals infected with HTLV-I (MT-2, HuT-102, FS, EG, SP) and HTLV-II (Mo-T, H2A, H2E) demonstrated a marked increase in constitutive expression of LIF and IL-6 transcripts, as compared with uninfected cell lines (HuT-78, Jurkat) [28].

Analytical, diagnostic and therapeutic context of Human T-lymphotropic virus 2

• RT-PCR demonstrated active expression of the HTLV-II regulatory protein Tax in the infected CD8+ T lymphocyte population, and it was further shown that Tax transactivates the promoters of MIP-1beta and RANTES [29].
• A series of synthetic peptides derived from the envelope glycoprotein of human T lymphotropic virus type II (HTLV-II) was used in an enzyme immunoassay to determine the immunodominant epitopes of envelope glycoprotein [30].
• This antibody (clone 6C2) was directed to an epitope within domain 4 (amino acids 210 to 306) of the retroviral env gene and reacted with envelope proteins in both HTLV-I and HTLV-II, as determined by immunoprecipitation, solid-phase binding, and immunoblotting [31].
• Sequence analysis of an amplified fragment of 172 nucleotides within the gp21 of the env region (6469-6640) of four HTLV-II infected individuals revealed a new HTLV-II molecular variant of the subtype b diverging from the prototypes NRA and G12 by seven (4.1%) and five (2.9%) bases substitutions, respectively [32].
• Seroprevalences of 2.50% (1 of 40) and 1.43% (1 of 70) for HTLV-1 were observed among Wayku and San Francisco communities in the Amazon region of Peru, and seroprevalences of 4.54% (1 of 22) and 2.38% (1 of 42) for HTLV-2 were observed among Boca Colorada and Galilea communities [33].

References