Human T-cell leukemia virus type 1 p8 protein increases cellular conduits and virus transmission
Open accessAbstract
The human T-cell leukemia virus type 1 (HTLV-1) is the cause of adult T-cell leukemia/lymphoma as well as tropical spastic paraparesis/HTLV-1–associated myelopathy. HTLV-1 is transmitted to T cells through the virological synapse and by extracellular viral assemblies. Here, we uncovered an additional mechanism of virus transmission that is regulated by the HTLV-1–encoded p8 protein. We found that the p8 protein, known to anergize T cells, is also able to increase T-cell contact through lymphocyte function-associated antigen-1 clustering. In addition, p8 augments the number and length of cellular conduits among T cells and is transferred to neighboring T cells through these conduits. p8, by establishing a T-cell network, enhances the envelope-dependent transmission of HTLV-1. Thus, the ability of p8 to simultaneously anergize and cluster T cells, together with its induction of cellular conduits, secures virus propagation while avoiding the host's immune surveillance. This work identifies p8 as a viral target for the development of therapeutic strategies that may limit the expansion of infected cells in HTLV-1 carriers and decrease HTLV-1–associated morbidity.
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HTLV-1 p8 protein plays an important role in transmission through conduits; p8 increases number and length of conduits, enhances intercellular contacts, induces LFA-1 clustering, translocates along conduits into recipient T cells, suppresses TCR signaling, leads to T cell anergy, and attenuates immune recognition of infected cells.
“The viral p8 protein plays an important role in the transmission of HTLV-1 through conduits. p8 is generated by a two-step proteolytic cleavage of the p12 protein encoded by open reading frame 1 (orf-1) in the HTLV-1 genome [117]. p8 increases the number and length of conduits, and enhances intercellular contacts, inducing clustering of LFA-1. Furthermore, p8 is rapidly translocated along conduits”
From HIV-1 and HTLV-1 Transmission Modes: Mechanisms and Importance for Virus Spread (2022) · cites this paper as [116]
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Omsland, M., Pise-Masison, C., Fujikawa, D., Galli, V., Fenizia, C., Parks, R. W., Gjertsen, B. T., Franchini, G., & Andresen, V. (2018) · Scientific Reports · doi:10.1038/s41598-018-29391-w · Cited by 71 · see citing works
Self-citationHIV-1 and HTLV-1 Transmission Modes: Mechanisms and Importance for Virus Spread
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“In addition to p8, the viral proteins, Gag and Env, are detected in conduits, whereas the mature viral particles can be at the contacts of a conduit with a cell body, or with another conduit [116].”
Background
- Authors
- Van Prooyen, N., Gold, H., Andresen, V., Schwartz, O., Jones, K., Ruscetti, F., Lockett, S., Gudla, P., Venzon, D., & Franchini, G.
- Affiliations
- Animal Models Retroviral Vaccine Section, Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892;
- National Institutes of Health (US)
- National Cancer Institute (US)
- Frederick National Laboratory for Cancer Research (US)
- Corresponding author
- Franchini, Genoveffa
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2010-11-12
- Volume
- 107
- Issue
- 48
- Pages
- 20738-20743
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2996430
- OpenAlex
- W2038365894
- Cited by
- 178
- References
- 7
- Citations by year
- 2026: 4 · 2025: 10 · 2024: 7 · 2023: 11 · 2022: 12 · 2021: 11 · 2020: 16 · 2019: 11 · 2018: 10 · 2017: 17 · 2016: 7 · 2015: 9 · 2014: 10 · 2013: 18 · 2012: 12
- FWCI
- 5.91
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute (HHSN261200800001E)
- National Institutes of Health (#HHSN261200800001E, HHSN261200800001C, Contract HHSN261200800001E)
- National Cancer Institute (Contract HHSN261200800001E, HHSN261200800001E))
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and Retrovirus Studies
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Health Sciences › Medicine › Oncology › Viral-associated cancers and disorders
- Keywords
- HTLV-1, p8 protein, virus transmission, T cell anergy, virological synapse, adult T-cell leukemia/lymphoma, tropical spastic paraparesis
- MeSH terms
- Cell Communication, Humans, Kinetics, T-Lymphocytes, Viral Proteins, Human T-lymphotropic virus 1, HTLV-I Infections, Jurkat Cells
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