HTLV-1 p13 Protein Hijacks Macrophage Polarization and Promotes T-Cell Recruitment
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 func...
Saved in:
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-03-01
|
| Series: | Viruses |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4915/17/4/471 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849714929027776512 |
|---|---|
| author | Ramona Moles Maria Omsland Cynthia A. Pise-Masison Jeffrey J. Subleski Daniel W. McVicar Sarkis Sarkis Anna Gutowska Luca Schifanella Melvin Doster Robyn Washington-Parks Vincenzo Ciminale Genoveffa Franchini |
| author_facet | Ramona Moles Maria Omsland Cynthia A. Pise-Masison Jeffrey J. Subleski Daniel W. McVicar Sarkis Sarkis Anna Gutowska Luca Schifanella Melvin Doster Robyn Washington-Parks Vincenzo Ciminale Genoveffa Franchini |
| author_sort | Ramona Moles |
| collection | DOAJ |
| description | 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<sup>+</sup> 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<sup>+</sup> T cells, the primary target of the virus, potentially facilitating the spread of viral infection and the development of disease. |
| format | Article |
| id | doaj-art-47bf4cccdef3457ab2962ba9f0b4cf00 |
| institution | DOAJ |
| issn | 1999-4915 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj-art-47bf4cccdef3457ab2962ba9f0b4cf002025-08-20T03:13:33ZengMDPI AGViruses1999-49152025-03-0117447110.3390/v17040471HTLV-1 p13 Protein Hijacks Macrophage Polarization and Promotes T-Cell RecruitmentRamona Moles0Maria Omsland1Cynthia A. Pise-Masison2Jeffrey J. Subleski3Daniel W. McVicar4Sarkis Sarkis5Anna Gutowska6Luca Schifanella7Melvin Doster8Robyn Washington-Parks9Vincenzo Ciminale10Genoveffa Franchini11Animal Models and Retroviral Vaccines Section, Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USAAnimal Models and Retroviral Vaccines Section, Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USAAnimal Models and Retroviral Vaccines Section, Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USACancer and Innovation Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USACancer and Innovation Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USAAnimal Models and Retroviral Vaccines Section, Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USAAnimal Models and Retroviral Vaccines Section, Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USAAnimal Models and Retroviral Vaccines Section, Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USAAnimal Models and Retroviral Vaccines Section, Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USAAnimal Models and Retroviral Vaccines Section, Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USADepartment of Surgery, Oncology and Gastroenterology, University of Padua, 35122 Padua, ItalyAnimal Models and Retroviral Vaccines Section, Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USAThe 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<sup>+</sup> 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<sup>+</sup> T cells, the primary target of the virus, potentially facilitating the spread of viral infection and the development of disease.https://www.mdpi.com/1999-4915/17/4/471HTLV-1p13viral proteinmitochondriamonocytesmacrophages |
| spellingShingle | Ramona Moles Maria Omsland Cynthia A. Pise-Masison Jeffrey J. Subleski Daniel W. McVicar Sarkis Sarkis Anna Gutowska Luca Schifanella Melvin Doster Robyn Washington-Parks Vincenzo Ciminale Genoveffa Franchini HTLV-1 p13 Protein Hijacks Macrophage Polarization and Promotes T-Cell Recruitment Viruses HTLV-1 p13 viral protein mitochondria monocytes macrophages |
| title | HTLV-1 p13 Protein Hijacks Macrophage Polarization and Promotes T-Cell Recruitment |
| title_full | HTLV-1 p13 Protein Hijacks Macrophage Polarization and Promotes T-Cell Recruitment |
| title_fullStr | HTLV-1 p13 Protein Hijacks Macrophage Polarization and Promotes T-Cell Recruitment |
| title_full_unstemmed | HTLV-1 p13 Protein Hijacks Macrophage Polarization and Promotes T-Cell Recruitment |
| title_short | HTLV-1 p13 Protein Hijacks Macrophage Polarization and Promotes T-Cell Recruitment |
| title_sort | htlv 1 p13 protein hijacks macrophage polarization and promotes t cell recruitment |
| topic | HTLV-1 p13 viral protein mitochondria monocytes macrophages |
| url | https://www.mdpi.com/1999-4915/17/4/471 |
| work_keys_str_mv | AT ramonamoles htlv1p13proteinhijacksmacrophagepolarizationandpromotestcellrecruitment AT mariaomsland htlv1p13proteinhijacksmacrophagepolarizationandpromotestcellrecruitment AT cynthiaapisemasison htlv1p13proteinhijacksmacrophagepolarizationandpromotestcellrecruitment AT jeffreyjsubleski htlv1p13proteinhijacksmacrophagepolarizationandpromotestcellrecruitment AT danielwmcvicar htlv1p13proteinhijacksmacrophagepolarizationandpromotestcellrecruitment AT sarkissarkis htlv1p13proteinhijacksmacrophagepolarizationandpromotestcellrecruitment AT annagutowska htlv1p13proteinhijacksmacrophagepolarizationandpromotestcellrecruitment AT lucaschifanella htlv1p13proteinhijacksmacrophagepolarizationandpromotestcellrecruitment AT melvindoster htlv1p13proteinhijacksmacrophagepolarizationandpromotestcellrecruitment AT robynwashingtonparks htlv1p13proteinhijacksmacrophagepolarizationandpromotestcellrecruitment AT vincenzociminale htlv1p13proteinhijacksmacrophagepolarizationandpromotestcellrecruitment AT genoveffafranchini htlv1p13proteinhijacksmacrophagepolarizationandpromotestcellrecruitment |