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The relative contributions of infectious and mitotic spread to HTLV-1 persistence.
- Source :
-
PLoS computational biology [PLoS Comput Biol] 2020 Sep 17; Vol. 16 (9), pp. e1007470. Date of Electronic Publication: 2020 Sep 17 (Print Publication: 2020). - Publication Year :
- 2020
-
Abstract
- Human T-lymphotropic virus type-1 (HTLV-1) persists within hosts via infectious spread (de novo infection) and mitotic spread (infected cell proliferation), creating a population structure of multiple clones (infected cell populations with identical genomic proviral integration sites). The relative contributions of infectious and mitotic spread to HTLV-1 persistence are unknown, and will determine the efficacy of different approaches to treatment. The prevailing view is that infectious spread is negligible in HTLV-1 persistence beyond early infection. However, in light of recent high-throughput data on the abundance of HTLV-1 clones, and recent estimates of HTLV-1 clonal diversity that are substantially higher than previously thought (typically between 104 and 105 HTLV-1+ T cell clones in the body of an asymptomatic carrier or patient with HTLV-1-associated myelopathy/tropical spastic paraparesis), ongoing infectious spread during chronic infection remains possible. We estimate the ratio of infectious to mitotic spread using a hybrid model of deterministic and stochastic processes, fitted to previously published HTLV-1 clonal diversity estimates. We investigate the robustness of our estimates using three alternative estimators. We find that, contrary to previous belief, infectious spread persists during chronic infection, even after HTLV-1 proviral load has reached its set point, and we estimate that between 100 and 200 new HTLV-1 clones are created and killed every day. We find broad agreement between all estimators. The risk of HTLV-1-associated malignancy and inflammatory disease is strongly correlated with proviral load, which in turn is correlated with the number of HTLV-1-infected clones, which are created by de novo infection. Our results therefore imply that suppression of de novo infection may reduce the risk of malignant transformation.<br />Competing Interests: The authors have declared that no competing interests exist.
- Subjects :
- CD4-Positive T-Lymphocytes virology
Humans
Mitosis genetics
Mitosis physiology
Models, Biological
Proviruses genetics
Proviruses pathogenicity
Viral Load genetics
Virus Integration genetics
HTLV-I Infections physiopathology
HTLV-I Infections virology
Host-Pathogen Interactions genetics
Host-Pathogen Interactions physiology
Human T-lymphotropic virus 1 classification
Human T-lymphotropic virus 1 genetics
Human T-lymphotropic virus 1 pathogenicity
Subjects
Details
- Language :
- English
- ISSN :
- 1553-7358
- Volume :
- 16
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- PLoS computational biology
- Publication Type :
- Academic Journal
- Accession number :
- 32941445
- Full Text :
- https://doi.org/10.1371/journal.pcbi.1007470