title: Stable changes in CD4+ T lymphocyte miRNA expression after exposure to HIV-1.
abstract: MicroRNAs (miRNAs) inhibit HIV-1 expression by either modulating host innate immunity or by directly interfering with viral mRNAs. We evaluated the expression of 377 miRNAs in CD4(+) T cells from HIV-1 élite long-term nonprogressors (éLTNPs), naive patients, and multiply exposed uninfected (MEU) patients, and we observed that the éLTNP patients clustered with naive patients, whereas all MEU subjects grouped together. The discriminatory power of miRNAs showed that 21 miRNAs significantly differentiated éLTNP from MEU patients and 23 miRNAs distinguished naive from MEU patients, whereas only 1 miRNA (miR-155) discriminated éLTNP from naive patients. We proposed that miRNA expression may discriminate between HIV-1-infected and -exposed but negative patients. Analysis of miRNAs expression after exposure of healthy CD4(+) T cells to gp120 in vitro confirmed our hypothesis that a miRNA profile could be the result not only of a productive infection but also of the exposure to HIV-1 products that leave a signature in immune cells. The comparison of normalized Dicer and Drosha expression in ex vivo and in vitro condition revealed that these enzymes did not affect the change of miRNA profiles, supporting the existence of a Dicer-independent biogenesis pathway.
authors.affiliation: Department of Clinical Sciences, University of Milano, Milano, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Bignami
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Pilotti
authors.forename: Linda
authors.initials: L
authors.lastname: Bertoncelli
authors.forename: Paola
authors.initials: P
authors.lastname: Ronzi
authors.forename: Mariolina
authors.initials: M
authors.lastname: Gulli
authors.forename: Nelson
authors.initials: N
authors.lastname: Marmiroli
authors.forename: Giacomo
authors.initials: G
authors.lastname: Magnani
authors.forename: Marcello
authors.initials: M
authors.lastname: Pinti
authors.forename: Lucia
authors.initials: L
authors.lastname: Lopalco
authors.forename: Cristina
authors.initials: C
authors.lastname: Mussini
authors.forename: Roberta
authors.initials: R
authors.lastname: Ruotolo
authors.forename: Massimo
authors.initials: M
authors.lastname: Galli
authors.forename: Andrea
authors.initials: A
authors.lastname: Cossarizza
authors.forename: Claudio
authors.initials: C
authors.lastname: Casoli
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D015699:HIV Envelope Protein gp120 / Q000494:pharmacology; D015658:HIV Infections / Q000235:genetics* / Q000276:immunology* / Q000473:pathology / Q000821:virology; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D046228:Microarray Analysis; D008875:Middle Aged; D013997:Time Factors; D019562:Viral Load
chemical_list: D015699:HIV Envelope Protein gp120; D035683:MicroRNAs