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, Claudio Casoli

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Leukocytes of persons coinfected with HTLV-2 and HIV-1 secrete chemokines that prevent CCR5-dependent (R5) HIV-1 infection of CD4+ T cells and macrophages, with HTLV-2-induced MIP-1α as dominant HIV-1 inhibitory molecule. Two nonallelic genes code for CCL3 and CCL3L1 isoforms of MIP-1α, and the population-specific copy number of CCL3L1 exerts a profound effect on HIV-1 susceptibility and disease progression. Here, we demonstrate that CCL3L1 is secreted spontaneously by leukocytes of HTLV-2-infected persons and superinduced when cells of HTLV-2/HIV-1 multiply exposed-uninfected seronegative (MEU) persons were stimulated with HIV-1 Env peptides. The CCL3L1 median copy number in MEU, HTLV-2/HIV-1-coinfected long-term nonprogressors (LTNPs) and HIV-1-monoinfected LTNPs were 1, 2, and 3, respectively. An increased CCL3L1/CCL3 mRNA ratio versus PHA-activated healthy leukocytes was observed in both HIV-1-monoinfected LTNPs and in HTLV-2/HIV-1MEU subjects. An additional potential correlate of HTLV-2 infection was a rapid and persistent leukocyte secretion of GM-CSF and IFN-γ, 2 cytokines endowed with CCR5 down-regulation capacity. This study confirms a crucial protective role of CCL3L1 from both HIV infection and disease progression, highlighting a previously not described functional up-regulation of this chemokine variant in both HIV-positive and -negative persons infected with HTLV-2.

Original languageEnglish
Pages (from-to)1850-1856
Number of pages7
JournalBlood
Volume109
Issue number5
DOIs
Publication statusPublished - Mar 1 2007

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Human T-lymphotropic virus 2
Chemokines
HIV-1
Up-Regulation
T-cells
Macrophages
Granulocyte-Macrophage Colony-Stimulating Factor
Protein Isoforms
Leukocytes
Genes
Cytokines
Messenger RNA
Peptides
Molecules
HIV Infections
HIV Long-Term Survivors
Disease Progression
Deltaretrovirus Infections
HIV
Down-Regulation

ASJC Scopus subject areas

  • Hematology

Cite this

Pilotti, E., Elviri, L., Vicenzi, E., Bertazzoni, U., Re, M. C., Allibardi, S., ... Casoli, C. (2007). Postgenomic up-regulation of CCL3L1 expression in HTLV-2-infected persons curtails HIV-1 replication. Blood, 109(5), 1850-1856. https://doi.org/10.1182/blood-2006-07-036046

Postgenomic up-regulation of CCL3L1 expression in HTLV-2-infected persons curtails HIV-1 replication. / Pilotti, Elisabetta; Elviri, Lisa; Vicenzi, Elisa; Bertazzoni, Umberto; Re, Maria Carla; Allibardi, Sonia; Poli, Guido; Casoli, Claudio.

In: Blood, Vol. 109, No. 5, 01.03.2007, p. 1850-1856.

Research output: Contribution to journalArticle

Pilotti, E, Elviri, L, Vicenzi, E, Bertazzoni, U, Re, MC, Allibardi, S, Poli, G & Casoli, C 2007, 'Postgenomic up-regulation of CCL3L1 expression in HTLV-2-infected persons curtails HIV-1 replication', Blood, vol. 109, no. 5, pp. 1850-1856. https://doi.org/10.1182/blood-2006-07-036046
Pilotti, Elisabetta ; Elviri, Lisa ; Vicenzi, Elisa ; Bertazzoni, Umberto ; Re, Maria Carla ; Allibardi, Sonia ; Poli, Guido ; Casoli, Claudio. / Postgenomic up-regulation of CCL3L1 expression in HTLV-2-infected persons curtails HIV-1 replication. In: Blood. 2007 ; Vol. 109, No. 5. pp. 1850-1856.
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