Publications
111 results found
Laydon DJ, Melamed A, Sim A, et al., 2014, Quantification of HTLV-1 Clonality and TCR Diversity, PLOS COMPUTATIONAL BIOLOGY, Vol: 10
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- Citations: 53
Elemans M, Florins A, Willems L, et al., 2014, Rates of CTL Killing in Persistent Viral Infection In Vivo, PLOS COMPUTATIONAL BIOLOGY, Vol: 10, ISSN: 1553-734X
The CD8+ cytotoxic T lymphocyte (CTL) response is an important defence against viral invasion. Although CTL-mediated cytotoxicity has been widely studied for many years, the rate at which virus-infected cells are killed in vivo by the CTL response is poorly understood. To date the rate of CTL killing in vivo has been estimated for three virus infections but the estimates differ considerably, and killing of HIV-1-infected cells was unexpectedly low. This raises questions about the typical anti-viral capability of CTL and whether CTL killing is abnormally low in HIV-1. We estimated the rate of killing of infected cells by CD8+ T cells in two distinct persistent virus infections: sheep infected with Bovine Leukemia Virus (BLV) and humans infected with Human T Lymphotropic Virus type 1 (HTLV-1) which together with existing data allows us to study a total of five viruses in parallel. Although both BLV and HTLV-1 infection are characterised by large expansions of chronically activated CTL with immediate effector function ex vivo and no evidence of overt immune suppression, our estimates are at the lower end of the reported range. This enables us to put current estimates into perspective and shows that CTL killing of HIV-infected cells may not be atypically low. The estimates at the higher end of the range are obtained in more manipulated systems and may thus represent the potential rather than the realised CTL efficiency.
Seich al Basatena NK, Chatzimichalis K, Graw F, et al., 2013, Can Non-Lytic CD8+ T cells Drive HIV-1 Escape, PLOS Pathogens, Vol: 11
Westera L, Drylewicz J, den Braber I, et al., 2013, Closing the gap between T-cell life span estimates from stable isotope-labeling studies in mice and humans, BLOOD, Vol: 122, Pages: 2205-2212, ISSN: 0006-4971
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- Citations: 87
Bangham C, Cook L, Laydon D, et al., 2013, Clonality, latency and integration of HTLV-1 in vivo, RETROVIROLOGY, Vol: 10, Pages: S3-S3, ISSN: 1742-4690
Bangham C, Cook L, Laydon D, et al., 2013, Clonality, latency and integration of HTLV-1 in vivo, Retrovirology, Vol: 10
Gillet NA, Cook L, Laydon DJ, et al., 2013, Strongyloidiasis and Infective Dermatitis Alter Human T Lymphotropic Virus-1 Clonality <i>in vivo</i>, PLOS PATHOGENS, Vol: 9, ISSN: 1553-7374
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- Citations: 52
Cook LB, Elemans M, Rowan AG, et al., 2013, HTLV-1: Persistence and pathogenesis, VIROLOGY, Vol: 435, Pages: 131-140, ISSN: 0042-6822
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- Citations: 72
Gillet NA, Gutiérrez G, Rodriguez SM, et al., 2013, Massive depletion of bovine leukemia virus proviral clones located in genomic transcriptionally active sites during primary infection., PLoS Pathog, Vol: 9
Deltaretroviruses such as human T-lymphotropic virus type 1 (HTLV-1) and bovine leukemia virus (BLV) induce a persistent infection that remains generally asymptomatic but can also lead to leukemia or lymphoma. These viruses replicate by infecting new lymphocytes (i.e. the infectious cycle) or via clonal expansion of the infected cells (mitotic cycle). The relative importance of these two cycles in viral replication varies during infection. The majority of infected clones are created early before the onset of an efficient immune response. Later on, the main replication route is mitotic expansion of pre-existing infected clones. Due to the paucity of available samples and for ethical reasons, only scarce data is available on early infection by HTLV-1. Therefore, we addressed this question in a comparative BLV model. We used high-throughput sequencing to map and quantify the insertion sites of the provirus in order to monitor the clonality of the BLV-infected cells population (i.e. the number of distinct clones and abundance of each clone). We found that BLV propagation shifts from cell neoinfection to clonal proliferation in about 2 months from inoculation. Initially, BLV proviral integration significantly favors transcribed regions of the genome. Negative selection then eliminates 97% of the clones detected at seroconversion and disfavors BLV-infected cells carrying a provirus located close to a promoter or a gene. Nevertheless, among the surviving proviruses, clone abundance positively correlates with proximity of the provirus to a transcribed region. Two opposite forces thus operate during primary infection and dictate the fate of long term clonal composition: (1) initial integration inside genes or promoters and (2) host negative selection disfavoring proviruses located next to transcribed regions. The result of this initial response will contribute to the proviral load set point value as clonal abundance will benefit from carrying a provirus in transcribed region
O'Connor GM, Al Basatena N-KS, Olavarria V, et al., 2012, In contrast to HIV, KIR3DS1 does not influence outcome in HTLV-1 retroviral infection, HUMAN IMMUNOLOGY, Vol: 73, Pages: 783-787, ISSN: 0198-8859
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- Citations: 7
Elemans M, al Basatena N-KS, Asquith B, 2012, The Efficiency of the Human CD8+T Cell Response: How Should We Quantify It, What Determines It, and Does It Matter?, PLOS COMPUTATIONAL BIOLOGY, Vol: 8
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- Citations: 17
Goetze JP, Hunter I, Lippert SK, et al., 2012, Processing-independent analysis of peptide hormones and prohormones in plasma, FRONTIERS IN BIOSCIENCE-LANDMARK, Vol: 17, Pages: 1804-1815, ISSN: 1093-9946
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- Citations: 17
Florins A, de Brogniez A, Elemans M, et al., 2012, Viral Expression Directs the Fate of B Cells in Bovine Leukemia Virus-Infected Sheep, JOURNAL OF VIROLOGY, Vol: 86, Pages: 621-624, ISSN: 0022-538X
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- Citations: 19
Olindo S, Belrose G, Gillet N, et al., 2011, Safety of long-term treatment of HAM/TSP patients with valproic acid, BLOOD, Vol: 118, Pages: 6306-6309, ISSN: 0006-4971
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- Citations: 34
Best I, Lopez G, Talledo M, et al., 2011, Short Communication An Interferon-γ ELISPOT Assay with Two Cytotoxic T Cell Epitopes Derived from HTLV-1 Tax Region 161-233 Discriminates HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis Patients from Asymptomatic HTLV-1 Carriers in a Peruvian Population, AIDS RESEARCH AND HUMAN RETROVIRUSES, Vol: 27, Pages: 1207-1212, ISSN: 0889-2229
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- Citations: 2
Seich al Basatena, Macnamara, Vine, et al., 2011, KIR2DL2 enhances protective and detrimental HLA class I-mediated immunity in chronic viral infection, PLoS Pathogens
al Basatena N-KS, MacNamara A, Vine AM, et al., 2011, <i>KIR2DL2</i> Enhances Protective and Detrimental HLA Class I-Mediated Immunity in Chronic Viral Infection, PLOS PATHOGENS, Vol: 7, ISSN: 1553-7366
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- Citations: 53
Elemans M, al Basatena N-KS, Klatt NR, et al., 2011, Why Don't CD8+T Cells Reduce the Lifespan of SIV-Infected Cells In Vivo?, PLOS COMPUTATIONAL BIOLOGY, Vol: 7
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- Citations: 25
Elemans M, Thiebaut R, Kaur A, et al., 2011, Quantification of the Relative Importance of CTL, B Cell, NK Cell, and Target Cell Limitation in the Control of Primary SIV-Infection, PLOS COMPUTATIONAL BIOLOGY, Vol: 7
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- Citations: 19
Hilburn S, Rowan A, Demontis M-A, et al., 2011, In vivo Expression of Human T-lymphotropic Virus Type 1 Basic Leucine-Zipper Protein Generates Specific CD8+and CD4+T-Lymphocyte Responses that Correlate with Clinical Outcome, JOURNAL OF INFECTIOUS DISEASES, Vol: 203, Pages: 529-536, ISSN: 0022-1899
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- Citations: 53
Asquith B, Borghans J, 2011, Modelling lymphocyte dynamics in vivo, Current Mathematical Models in Immunology, Publisher: Springer
al Basatena N-KS, Macnamara A, Vine AM, et al., 2010, <i>KIR2DL2</i> enhances protective and detrimental HLA class I-mediated immunity in chronic viral infection, Annual Congress of the British-Society-for-Immunology, Publisher: WILEY-BLACKWELL PUBLISHING, INC, Pages: 148-148, ISSN: 0019-2805
Kadolsky UD, Asquith B, 2010, Quantifying the Impact of Human Immunodeficiency Virus-1 Escape From Cytotoxic T-Lymphocytes, PLOS COMPUTATIONAL BIOLOGY, Vol: 6, ISSN: 1553-734X
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- Citations: 18
MacNamara A, Rowan A, Hilburn S, et al., 2010, HLA Class I Binding of HBZ Determines Outcome in HTLV-1 Infection, PLOS PATHOGENS, Vol: 6, ISSN: 1553-7366
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- Citations: 107
Macnamara A, Rowan A, Asquith B, et al., 2009, HLA Class I Binding of HBZ is Associated with Reduced HTLV-I Proviral Load and HAM/TSP Prevalence, 14th International Conference on Human Retrovirology HTLV and Related Retroviruses, Publisher: MARY ANN LIEBERT INC, Pages: 1258-1259, ISSN: 0889-2229
MacNamara A, Rowan A, Kadolsky U, et al., 2009, HBZ Binding to HLA Class 1 Determines the Outcome of HTLV-1, 14th International Conference on Human Retrovirology HTLV and Related Retroviruses, Publisher: MARY ANN LIEBERT INC, Pages: 1201-1202, ISSN: 0889-2229
Rowan A, Macnamara A, Asquith B, et al., 2009, Sensitivity and Efficiency of HTLV-1-Specific Cytotoxic T Lymphocytes, 14th International Conference on Human Retrovirology HTLV and Related Retroviruses, Publisher: MARY ANN LIEBERT INC, Pages: 1286-1287, ISSN: 0889-2229
Asquith B, Borghans JAM, Ganusov VV, et al., 2009, Lymphocyte kinetics in health and disease (vol 30, pg 182, 2009), TRENDS IN IMMUNOLOGY, Vol: 30, Pages: 467-467, ISSN: 1471-4906
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- Citations: 2
Florins A, Reichert M, Asquith B, et al., 2009, Earlier onset of delta-retrovirus-induced leukemia after splenectomy, PLoS One, Vol: 4, Pages: 1-7, ISSN: 1932-6203
Infection by δ-retroviruses such as human T-lymphotropic virus type 1 (HTLV-1) and bovine leukemia virus (BLV) is mostly asymptomatic. Indeed, only a minority (<5%) of δ-retrovirus infected hosts will develop either lymphoproliferative or neurodegenerative diseases after long latency periods. In fact, the host immune response is believed to tightly control viral replication but this assumption has not been definitely proven in vivo. Here, we provide direct experimental evidence demonstrating that integrity of the spleen is required to control pathogenesis. In the BLV model, we show that asplenia decreases efficiency of the immune response and induces an imbalance in cell dynamics resulting in accelerated onset of leukemia. These observations enlighten a potential threat in splenectomized HTLV-1 carriers and justify a regular preventive evaluation.
Lezin A, Olindo S, Belrose G, et al., 2009, Gene activation therapy: from the BLV model to HAM/TSP patients., Front Biosci (Schol Ed), Vol: 1, Pages: 205-215
HTLV-1 (human T-lymphotropic virus type 1) and BLV (bovine leukemia virus) are two related retroviruses infecting CD4+ and B lymphocytes in humans and ruminants, respectively. During infection, the host-pathogen interplay is characterized by very dynamic kinetics resulting in equilibrium between the virus, which attempts to proliferate, and the immune response, which seeks to exert tight control of the virus. A major determinant of disease induction by both viruses is the accumulation of provirus in peripheral blood. In the absence of viral proteins, virus infected cells escape recognition and destruction by the host immune response. We propose a novel therapeutic strategy based on transient activation of viral expression using epigenetic modulators; this exposes infected cells to the immune response and results in significant reductions in proviral loads. In the absence of satisfactory therapies, this viral gene-activation strategy might delay progression, or even be curative, for HTLV-1 induced myelopathy / tropical spastic paraparesis (HAM/TSP).
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