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Volume 17
Issue 4
10.3390/v17040471
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Article

HTLV-1 p13 Protein Hijacks Macrophage Polarization and Promotes T-Cell Recruitment

by
Ramona Moles
1,2,*,
Maria Omsland
1,3,
Cynthia A. Pise-Masison
1,
Jeffrey J. Subleski
4,
Daniel W. McVicar
4,
Sarkis Sarkis
1,
Anna Gutowska
1,
Luca Schifanella
1,
Melvin Doster
1,
Robyn Washington-Parks
1,
Vincenzo Ciminale
5,6 and
Genoveffa Franchini
1,*
1
Animal Models and Retroviral Vaccines Section, Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
2
Department of Cell and Molecular Biology, Center for Immunology and Microbial Research, Cancer Center and Research Institute, University of Mississippi Medical Center, Jackson, MS 39216, USA
3
Department of Safety, Chemistry, and Biomedical Laboratory Sciences, Western Norway University of Applied Science, 5063 Bergen, Norway
4
Cancer and Innovation Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA
5
Department of Surgery, Oncology and Gastroenterology, University of Padua, 35122 Padua, Italy
6
Veneto Institute of Oncology IOV—IRCCS, 35128 Padua, Italy
*
Authors to whom correspondence should be addressed.
Viruses 2025, 17(4), 471; https://doi.org/10.3390/v17040471
Submission received: 26 February 2025 / Revised: 20 March 2025 / Accepted: 21 March 2025 / Published: 26 March 2025
(This article belongs to the Special Issue Human T-Cell Leukemia Virus (HTLV) Infection and Treatment)
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Abstract

The human T-cell leukemia type-1 (HTLV-1) retrovirus establishes chronic life-long infection in a fraction of infected individuals associated with severe pathological conditions. Although the mechanism driving disease development is not fully understood, current evidence indicates the essential functions of viral regulatory proteins. Among these, the p13 protein has previously been shown to localize to the inner mitochondrial membrane in T cells, altering mitochondrial biology and T-cell function. While CD4+ T cells are the primary cell target of HTLV-1 infection, genomic viral DNA has also been detected in monocytes, macrophages, and dendritic cells, which orchestrate innate and adaptive immunity and play a critical role in protecting against virus-induce diseases by establishing the appropriate balance of pro and anti-inflammatory responses. Given the central role of mitochondria in monocyte differentiation, we investigated the effect of p13 in monocytes/macrophages and found that by localizing to mitochondria, p13 affects mitochondrial respiration. Moreover, we demonstrate that p13 expression affects macrophage polarization to favor the recruitment of CD4+ T cells, the primary target of the virus, potentially facilitating the spread of viral infection and the development of disease.
Keywords: HTLV-1; p13; viral protein; mitochondria; monocytes; macrophages; cytokines; adult-T-cell leukemia/lymphoma; ATLL; HTLV-1 associated myelopathy/tropical spastic paraparesis; HAM/TSP HTLV-1; p13; viral protein; mitochondria; monocytes; macrophages; cytokines; adult-T-cell leukemia/lymphoma; ATLL; HTLV-1 associated myelopathy/tropical spastic paraparesis; HAM/TSP

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MDPI and ACS Style

Moles, R.; Omsland, M.; Pise-Masison, C.A.; Subleski, J.J.; McVicar, D.W.; Sarkis, S.; Gutowska, A.; Schifanella, L.; Doster, M.; Washington-Parks, R.; et al. HTLV-1 p13 Protein Hijacks Macrophage Polarization and Promotes T-Cell Recruitment. Viruses 2025, 17, 471. https://doi.org/10.3390/v17040471

AMA Style

Moles R, Omsland M, Pise-Masison CA, Subleski JJ, McVicar DW, Sarkis S, Gutowska A, Schifanella L, Doster M, Washington-Parks R, et al. HTLV-1 p13 Protein Hijacks Macrophage Polarization and Promotes T-Cell Recruitment. Viruses. 2025; 17(4):471. https://doi.org/10.3390/v17040471

Chicago/Turabian Style

Moles, Ramona, Maria Omsland, Cynthia A. Pise-Masison, Jeffrey J. Subleski, Daniel W. McVicar, Sarkis Sarkis, Anna Gutowska, Luca Schifanella, Melvin Doster, Robyn Washington-Parks, and et al. 2025. "HTLV-1 p13 Protein Hijacks Macrophage Polarization and Promotes T-Cell Recruitment" Viruses 17, no. 4: 471. https://doi.org/10.3390/v17040471

APA Style

Moles, R., Omsland, M., Pise-Masison, C. A., Subleski, J. J., McVicar, D. W., Sarkis, S., Gutowska, A., Schifanella, L., Doster, M., Washington-Parks, R., Ciminale, V., & Franchini, G. (2025). HTLV-1 p13 Protein Hijacks Macrophage Polarization and Promotes T-Cell Recruitment. Viruses, 17(4), 471. https://doi.org/10.3390/v17040471

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