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Blood, 1 March 2007, Vol. 109, No. 5, pp. 1792. This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Zella, D. Search for Related Content PubMed Articles by Zella, D. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CHEMOKINES Comment on Pilotti et al, page 1850 HTLV-IIb reduces HIV infection Davide Zella INSTITUTE OF HUMAN VIROLOGY The article of Pilotti and colleagues aims to elucidate the anti-HIV mechanism(s) related to HTLV-II coinfection in intravenous drug users (IDUs). The authors demonstrate spontaneous production in vitro of an isoform of MIP-1 (CCL3L1) in PBMCs from HTLV-II–infected subjects, and this isoform was the major determinant of anti-HIV activity in coinfected HTLV/HIV subjects, possibly due to interference with chemokine receptor CCR5. Additional studies provide indirect evidence that the mechanism should act at a transcriptional level. First isolated in association with a rare form of hairy cell leukemia,1 and subsequently classified in 2 different subtypes (a and b), human T-lymphotropic virus type II (HTLV-II) has been associated with several lymphoproliferative manifestations, although its direct role in causing a disease has never been unequivocally demonstrated. Based on evidence in vitro and epidemiologic studies, it has been speculated that type a could exert a more detrimental role interacting with the immune system than type b. HTLV-II has been shown to be endemic among various American-Indian populations in North America, in Panama, and in South America. HTLV-II can be transmitted in 3 ways: mother-to-child transmission (associated mainly with prolonged breastfeeding), mainly in tropical developing countries; sexual transmission (mainly from men to women); and parenteral transmission (by needle sharing and transfusion). HTLV-II infection has also been endemic for the past 10 to 20 years among intravenous drug users (IDUs) in Europe, especially in Italy, Spain, and Ireland, as well as in North America. From epidemiologic studies, it was soon clear that HTLV-II did not cause any fast progression to acquired immunodeficiency syndrome (AIDS) in IDUs, but on the contrary it was surprisingly associated with a delayed progression. It was only after the discovery of chemokines as natural inhibitors of human immunodeficiency virus (HIV) infection,2 that the possible mechanism of HTLV-II protective action started to be elucidated. Indeed, an increased C-C chemokine production in certain coinfected patients was noted.3,4 The current article by Pilotti and colleagues provides a better comprehension of this mechanism. In fact, it appears that HTLV-II infection triggers production of CCL3L1, an isoform of MIP-1 that is primarily responsible for protection (see figure). This induction seems to act at a transcriptional level, though the authors do not provide any direct evidence to sustain this hypothesis. In addition, other "protective" cytokines were produced as a result of HTLV-II infection. The effect was noted not only in stimu-lated peripheral blood mononuclear cells (PBMCs), but also in unstimulated cells. The authors thus propose that HTLV-II confers a protective state able to reduce susceptibility to HIV infection. View larger version (54K): [in this window] [in a new window]   Kinetics of R5 and X4 virus production by primary cultures established from 3 HTLV-2/HIV-1MEU persons. See the complete figure in the article beginning on page 1850.   More studies are needed to determine how and why HTLV-IIb alters the cell programming apparatus to induce production of CCL3L1, protective cytokines, and a protective status against HIV. Eventually, this might result in a better understanding of the interactions between the virus and components of the immune system. It could also help in an understanding of how to induce such a protective staus. Footnotes The author declares no competing financial interests. REFERENCES Kalyanaraman VS, Sarngadharan MG, Robet-Guroff M, Miyoshi I, Golde D, Gallo RC. A new subtype of human-T-cell leukemia virus (HTLV-II) associated with a T-cell variant of hairy cell leukemia. Science 1982; 218:571–573.[Abstract/Free Full Text] Cocchi F, De Vico AL, Garzino-Demo A, Arya SK, Gallo RC, Lusso P. Identification of RANTES, MIP-1 alpha, and MIP-1 beta as the major HIV-suppressive factors produced by CD8+ T cells. Science 1995; 270:1811–1815.[Abstract/Free Full Text] Lewis MJ, Gautier VW, Wang XP, Kaplan MH, Hall WW. Spontaneous production of C-C chemokines by individuals infected with human T lymphotropic virus type II (HTLV-II) alone and in HTLV-II/HIV-1 coinfected individuals. J Immunol 2000; 165:4127–4132.[Abstract/Free Full Text] Casoli C, Vicenzi E, Cimarelli A, et al. HTLV-II down-regulates HIV-1 replication in IL-2 stimulated primary PBMC of coinfected individuals through expression of MIP-alpha. Blood 2000; 95:2760–2769.[Abstract/Free Full Text] CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Postgenomic up-regulation of CCL3L1 expression in HTLV-2–infected persons curtails HIV-1 replication Elisabetta Pilotti, Lisa Elviri, Elisa Vicenzi, Umberto Bertazzoni, Maria Carla Re, Sonia Allibardi, Guido Poli, and Claudio Casoli Blood 2007 109: 1850-1856. [Abstract] [Full Text] [PDF] This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Zella, D. Search for Related Content PubMed Articles by Zella, D. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?

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