scholarly journals Conservation of a Neutralization Epitope of Human T-cell Leukemia Virus Type 1 (HTLV-1) among Currently Endemic Clinical Isolates in Okinawa, Japan

Pathogens ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 82
Author(s):  
Mariko Mizuguchi ◽  
Yoshiaki Takahashi ◽  
Reiko Tanaka ◽  
Takuya Fukushima ◽  
Yuetsu Tanaka

Approximately one-tenth of the 10 million individuals living with human T-cell leukemia virus type-1 (HTLV-1) worldwide live in Japan. Most of these infected individuals live in the southwest region of Japan, including Okinawa prefecture; however, currently no prophylactic vaccine against HTLV-1 infection is available. For preventing the HTLV-1 spread, we previously generated a humanized monoclonal antibody (hu-LAT-27) that mediates both neutralization and antibody-dependent cellular cytotoxicity (ADCC). The neutralization epitope of LAT-27 is a linear amino acid sequence from residue 191 to 196 (Leu-Pro-His-Ser-Asn-Leu) of the HTLV-1 envelope gp46 protein. Here, we found that the LAT-27 epitope is well conserved among HTLV-1 clinical isolates prevalent in Okinawa. The hu-LAT-27 treatment inhibited syncytium formation by these clinical HTLV-1 isolates. Although an amino acid substitution at residue 192 in the LAT-27 epitope from proline to serine was found in a few HTLV-1 isolates, hu-LAT-27 could still react with a synthetic peptide carrying this amino acid substitution. These findings demonstrate the wide spectrum of hu-LAT-27 reactivity, suggesting that hu-LAT-27 may be a candidate drug for prophylactic passive immunization against HTLV-1 infection.

2003 ◽  
Vol 23 (23) ◽  
pp. 8751-8761 ◽  
Author(s):  
Yoshiyuki Hakata ◽  
Masami Yamada ◽  
Hisatoshi Shida

ABSTRACT Human CRM1 (hCRM1) functions in the Rex-mediated mRNA export of human T-cell leukemia virus type 1 (HTLV-1) as an export receptor and as an inducing factor for Rex multimerization on its cognate RNA. Although there are only 24 amino acid differences between hCRM1 and rat CRM1 (rCRM1), rCRM1 can hardly support Rex activity, suggesting a role for rCRM1 as a determinant restricting the host range of HTLV-1. Here, we used a series of mutants, which were generated by interchanging residues of these CRM1s, to examine the relationship of hCRM1 functions. The functions for Rex multimerization and binding to nuclear export signals are mapped to different amino acid residues, and these are separable, suggesting that CRM1 not only functions as an export receptor but also participates in the formation of the RNA export complex through higher-ordered interaction with Rex. The region for the interaction with RanBP3, comprising four residues (amino acids [aa] 411, 414, 474, and 481), and the region for Rex multimerization, including two residues (aa 411 and 414), form an overlapped domain. Our results provide the molecular basis underlying the species-specific ability of HTLV-1 to propagate in human cells.


1999 ◽  
Vol 73 (11) ◽  
pp. 9369-9376 ◽  
Author(s):  
Sophie Blanchard ◽  
Thérèse Astier-Gin ◽  
Béatrice Tallet ◽  
Daniel Moynet ◽  
Danielle Londos-Gagliardi ◽  
...  

ABSTRACT The nucleotide sequence of human T-cell leukemia virus type 1 (HTLV-1) is highly conserved, most strains sharing at least 95% sequence identity. This sequence conservation is also found in the viral env gene, which codes for the two envelope glycoproteins that play a major role in the induction of a protective immune response against the virus. However, recent reports have indicated that some variations in env sequences may induce incomplete cross-reactivity between HTLV-1 strains. To identify the amino acid changes that might be involved in the antigenicity of neutralizable epitopes, we constructed expression vectors coding for the envelope glycoproteins of two HTLV-1 isolates (2060 and 2072) which induced human antibodies with different neutralization patterns. The amino acid sequences of the envelope glycoproteins differed at four positions. Vectors coding for chimeric or point-mutated envelope proteins were derived from 2060 and 2072 HTLV-1 env genes. Syncytium formation induced by the wild-type or mutated envelope proteins was inhibited by human sera with different neutralizing specificities. We thus identified two amino acid changes, I173→V and A187→T, that play an important role in the antigenicity of neutralizable epitopes located in this region of the surface envelope glycoprotein.


2017 ◽  
Vol 55 (9) ◽  
pp. 2838-2849 ◽  
Author(s):  
Madoka Kuramitsu ◽  
Tsuyoshi Sekizuka ◽  
Tadanori Yamochi ◽  
Sanaz Firouzi ◽  
Tomoo Sato ◽  
...  

ABSTRACTWestern blotting (WB) for human T cell leukemia virus type 1 (HTLV-1) is performed to confirm anti-HTLV-1 antibodies detected at the initial screening of blood donors and in pregnant women. However, the frequent occurrence of indeterminate results is a problem with this test. We therefore assessed the cause of indeterminate WB results by analyzing HTLV-1 provirus genomic sequences. A quantitative PCR assay measuring HTLV-1 provirus in WB-indeterminate samples revealed that the median proviral load was approximately 100-fold lower than that of WB-positive samples (0.01 versus 0.71 copy/100 cells). Phylogenic analysis of the complete HTLV-1 genomes of WB-indeterminate samples did not identify any specific phylogenetic groups. When we analyzed the nucleotide changes in 19 HTLV-1 isolates from WB-indeterminate samples, we identified 135 single nucleotide substitutions, composed of four types, G to A (29%), C to T (19%), T to C (19%), and A to G (16%). In the most frequent G-to-A substitution, 64% occurred at GG dinucleotides, indicating that APOBEC3G is responsible for mutagenesis in WB-indeterminate samples. Moreover, interestingly, five WB-indeterminate isolates had nonsense mutations in Pol and/or Tax, Env, p12, and p30. These findings suggest that WB-indeterminate carriers have low production of viral antigens because of a combination of a low proviral load and mutations in the provirus, which may interfere with host recognition of HTLV-1 antigens.


1989 ◽  
Vol 160 (3) ◽  
pp. 363-370 ◽  
Author(s):  
M. Verdier ◽  
F. Denis ◽  
A. Sangare ◽  
F. Barin ◽  
G. Gershy-Damet ◽  
...  

Oncogene ◽  
2004 ◽  
Vol 23 (29) ◽  
pp. 4966-4974 ◽  
Author(s):  
Hyeon Ung Park ◽  
Jae-Hoon Jeong ◽  
Jay H Chung ◽  
John N Brady

2011 ◽  
Vol 85 (14) ◽  
pp. 6955-6962 ◽  
Author(s):  
S. Charoenthongtrakul ◽  
Q. Zhou ◽  
N. Shembade ◽  
N. S. Harhaj ◽  
E. W. Harhaj

2013 ◽  
Vol 1833 (6) ◽  
pp. 1542-1552 ◽  
Author(s):  
Chie Ishikawa ◽  
Hirochika Kawakami ◽  
Jun-Nosuke Uchihara ◽  
Masachika Senba ◽  
Naoki Mori

2020 ◽  
Vol 11 ◽  
Author(s):  
Kazuo Itabashi ◽  
Tokuo Miyazawa ◽  
Akihiko Sekizawa ◽  
Akifumi Tokita ◽  
Shigeru Saito ◽  
...  

2011 ◽  
Vol 85 (3) ◽  
pp. 1417-1417
Author(s):  
M. Tomita ◽  
A. Kikuchi ◽  
T. Akiyama ◽  
Y. Tanaka ◽  
N. Mori

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