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Title: Endemic versus epidemic viral spreads display distinct patterns of HTLV-2b replication

Abstract

As the replication pattern of leukemogenic PTLVs possesses a strong pathogenic impact, we investigated HTLV-2 replication in vivo in asymptomatic carriers belonging into 2 distinct populations infected by the same HTLV-2b subtype. They include epidemically infected American blood donors, in whom HTLV-2b has been present for only 30 years, and endemically infected Bakola Pygmies from Cameroon, characterized by a long viral endemicity (at least few generations). In blood donors, both the circulating proviral loads and the degree of infected cell proliferation were largely lower than those characterizing asymptomatic carriers infected with leukemogenic PTLVs (HTLV-1, STLV-1). This might contribute to explain the lack of known link between HTLV-2b infection and the development of malignancies in this population. In contrast, endemically infected individuals displayed high proviral loads resulting from the extensive proliferation of infected cells. The route and/or the duration of infection, viral genetic drift, host immune response, genetic background, co-infections or a combination thereof might have contributed to these differences between endemically and epidemically infected subjects. As the clonality pattern observed in endemically infected individuals is very reminiscent of that of leukemogenic PTLVs at the pre-leukemic stage, our results highlight the possible oncogenic effect of HTLV-2b infection in such population.

Authors:
 [1];  [1];  [1];  [2];  [3];  [1];  [4];  [4];  [5];  [6]
  1. Oncovirologie et Biotherapies, UMR5537-CNRS-Universite Claude Bernard, Centre Leon Berard, Lyon (France)
  2. (France)
  3. American Red Cross Blood Services, Chesapeake Region, Baltimore, MD 21215-3200 (United States)
  4. Unite d'Epidemiologie et Physiopathologie des Virus Oncogenes, Institut Pasteur, Paris (France)
  5. Department of Laboratory Medicine, University of California San Francisco, and Blood Systems Research Institute, San Francisco, California, CA 94143-0560 (United States)
  6. Oncovirologie et Biotherapies, UMR5537-CNRS-Universite Claude Bernard, Centre Leon Berard, Lyon (France) and Service d'Hematologie, Pavillon E, Hopital Edouard Herriot, Lyon (France). E-mail: wattel@lyon.fnclcc.fr
Publication Date:
OSTI Identifier:
20779452
Resource Type:
Journal Article
Resource Relation:
Journal Name: Virology; Journal Volume: 345; Journal Issue: 1; Other Information: DOI: 10.1016/j.virol.2005.08.026; PII: S0042-6822(05)00516-7; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; BLOOD; CARRIERS; CELL PROLIFERATION; EPIDEMIOLOGY; GENETIC VARIABILITY; IN VIVO; LEUKEMOGENESIS; NEOPLASMS

Citation Formats

Gabet, Anne-Sophie, Moules, Vincent, Sibon, David, Service d'Hematologie, Pavillon E, Hopital Edouard Herriot, Lyon, Nass, Catharie C., Mortreux, Franck, Mauclere, Philippe, Gessain, Antoine, Murphy, Edward L., and Wattel, Eric. Endemic versus epidemic viral spreads display distinct patterns of HTLV-2b replication. United States: N. p., 2006. Web. doi:10.1016/J.VIROL.2005.0.
Gabet, Anne-Sophie, Moules, Vincent, Sibon, David, Service d'Hematologie, Pavillon E, Hopital Edouard Herriot, Lyon, Nass, Catharie C., Mortreux, Franck, Mauclere, Philippe, Gessain, Antoine, Murphy, Edward L., & Wattel, Eric. Endemic versus epidemic viral spreads display distinct patterns of HTLV-2b replication. United States. doi:10.1016/J.VIROL.2005.0.
Gabet, Anne-Sophie, Moules, Vincent, Sibon, David, Service d'Hematologie, Pavillon E, Hopital Edouard Herriot, Lyon, Nass, Catharie C., Mortreux, Franck, Mauclere, Philippe, Gessain, Antoine, Murphy, Edward L., and Wattel, Eric. Sun . "Endemic versus epidemic viral spreads display distinct patterns of HTLV-2b replication". United States. doi:10.1016/J.VIROL.2005.0.
@article{osti_20779452,
title = {Endemic versus epidemic viral spreads display distinct patterns of HTLV-2b replication},
author = {Gabet, Anne-Sophie and Moules, Vincent and Sibon, David and Service d'Hematologie, Pavillon E, Hopital Edouard Herriot, Lyon and Nass, Catharie C. and Mortreux, Franck and Mauclere, Philippe and Gessain, Antoine and Murphy, Edward L. and Wattel, Eric},
abstractNote = {As the replication pattern of leukemogenic PTLVs possesses a strong pathogenic impact, we investigated HTLV-2 replication in vivo in asymptomatic carriers belonging into 2 distinct populations infected by the same HTLV-2b subtype. They include epidemically infected American blood donors, in whom HTLV-2b has been present for only 30 years, and endemically infected Bakola Pygmies from Cameroon, characterized by a long viral endemicity (at least few generations). In blood donors, both the circulating proviral loads and the degree of infected cell proliferation were largely lower than those characterizing asymptomatic carriers infected with leukemogenic PTLVs (HTLV-1, STLV-1). This might contribute to explain the lack of known link between HTLV-2b infection and the development of malignancies in this population. In contrast, endemically infected individuals displayed high proviral loads resulting from the extensive proliferation of infected cells. The route and/or the duration of infection, viral genetic drift, host immune response, genetic background, co-infections or a combination thereof might have contributed to these differences between endemically and epidemically infected subjects. As the clonality pattern observed in endemically infected individuals is very reminiscent of that of leukemogenic PTLVs at the pre-leukemic stage, our results highlight the possible oncogenic effect of HTLV-2b infection in such population.},
doi = {10.1016/J.VIROL.2005.0},
journal = {Virology},
number = 1,
volume = 345,
place = {United States},
year = {Sun Feb 05 00:00:00 EST 2006},
month = {Sun Feb 05 00:00:00 EST 2006}
}
  • HTLV-1 is more pathogenic than HTLV-2B. The difference is generally attributed to the properties of their individual transactivating Tax proteins. By using internal Flag-6His tagged Tax-1 and Tax-2B, which display transcriptional activities comparable to the untagged proteins and can be recognized by a single anti-Flag antibody, we demonstrate that Tax-2B is modified by ubiquitination and sumoylation. In addition, Tax2B is distributed in punctuate nuclear structures that include the RelA subunit of NF-{kappa}B, as has been previously demonstrated for Tax-1.
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  • To investigate novel NS1-interacting proteins, we conducted a yeast two-hybrid analysis, followed by co-immunoprecipitation assays. We identified heterogeneous nuclear ribonucleoprotein F (hnRNP-F) as a cellular protein interacting with NS1 during influenza A virus infection. Co-precipitation assays suggest that interaction between hnRNP-F and NS1 is a common and direct event among human or avian influenza viruses. NS1 and hnRNP-F co-localize in the nucleus of host cells, and the RNA-binding domain of NS1 directly interacts with the GY-rich region of hnRNP-F determined by GST pull-down assays with truncated proteins. Importantly, hnRNP-F expression levels in host cells indicate regulatory role on virus replication.more » hnRNP-F depletion by small interfering RNA (siRNA) shows 10- to 100-fold increases in virus titers corresponding to enhanced viral RNA polymerase activity. Our results delineate novel mechanism of action by which NS1 accelerates influenza virus replication by modulating normal cellular mRNA processes through direct interaction with cellular hnRNP-F protein.« less
  • Abstract not provided.