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TAX and HBZ: HFc Ɣ 1 Proteins As Targets for Passive Immunotherapy

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Abstract

Objectives: Human T leukemia virus type one (HTLV-1) causes two life-threatening diseases in around five percent of infected subjects, a T cell malignancy and a neurodegenerative disease. TAX and HBZ are the main virulence agents implicated in the manifestation of HTLV-1-associated diseases. Therefore, this study aims to produce these HTLV-1 factors as recombinant Fc fusion proteins to study the structures, their immunogenic properties as vaccines, and their capability to produce specific neutralization antibodies.

Materials And Methods: TAX and HBZ sequences were chosen from the NCBI-nucleotide database, then designed as human Fc chimers and cloned into . Produced proteins were purified by HiTrap affinity chromatography and subcutaneously injected into rabbits. Rabbit Abs were purified by batch chromatography, and their neutralization activities for the HTLV-1-infected MT-2 cell line were assessed. Furthermore, the protective abilities of recombinant proteins were evaluated in Tax or HBZ immunized rabbits by MT-2 cell line inoculation and measurement of HTLV-1-proviral load.

Results: Specific Abs against Tax and HBZ can eliminate 2 million MT-2 cells in 1/1000 dilution . In challenging assays, the immunization of the animals using Tax or HBZ had no protective activity as HTLV-1 PVL was still positive.

Conclusion: The result suggests that recombinant TAX and HBZ: hFcγ1 proteins can produce a proper humoral immune response. Therefore, they could be considered a passive immunotherapy source for HTLV-1-associated diseases, while total TAX and HBZ proteins are unsuitable as HTLV-1 vaccine candidates.

Citing Articles

Development of a Novel HTLV-1 Protease: Human Fcγ1 Recombinant Fusion Molecule in the CHO Eukaryotic Expression System.

Ahmadi Ghezeldasht S, Momen Heravi M, Valizadeh N, Rafatpanah H, Shamsian S, Mosavat A Appl Biochem Biotechnol. 2022; 195(3):1862-1876.

PMID: 36399306 PMC: 9673214. DOI: 10.1007/s12010-022-04259-y.

References
1.
de The G, Bomford R . An HTLV-I vaccine: why, how, for whom?. AIDS Res Hum Retroviruses. 1993; 9(5):381-6. DOI: 10.1089/aid.1993.9.381. View

2.
Zhao T . The Role of HBZ in HTLV-1-Induced Oncogenesis. Viruses. 2016; 8(2). PMC: 4776189. DOI: 10.3390/v8020034. View

3.
Rodriguez-Zuniga M, Cortez-Franco F, Qujiano-Gomero E . Adult T-Cell Leukemia/Lymphoma. Review of the Literature. Actas Dermosifiliogr (Engl Ed). 2018; 109(5):399-407. DOI: 10.1016/j.ad.2017.08.014. View

4.
Lovell S, Davis I, Arendall 3rd W, de Bakker P, Word J, Prisant M . Structure validation by Calpha geometry: phi,psi and Cbeta deviation. Proteins. 2003; 50(3):437-50. DOI: 10.1002/prot.10286. View

5.
Mozhgani S, Jaberi N, Rezaee S, Bustani R, Jazayeri S, Akbarin M . Evaluation of HTLV-1 HBZ and proviral load, together with host IFN λ3, in pathogenesis of HAM/TSP. J Med Virol. 2016; 89(6):1102-1107. DOI: 10.1002/jmv.24721. View