Nitazoxanide (Alinia (R), NTZ) and tizoxanide (TIZ), its active circulating metabolite, belong to a class of agents known as thiazolides (TZD) endowed with broad anti-infective activities. TIZ and RM-4848, the active metabolite of RM-5038, were shown to stimulate innate immunity in vitro. Because natural resistance to HIV-1 infection in HIV-exposed seronegative (HESN) individuals is suggested to be associated with strong innate immune responses, we verified whether TIZ and RM-4848 could reduce the in vitro infectiousness of HIV-1. Peripheral blood mononuclear cells (PBMCs) from 20 healthy donors were infected in vitro with HIV-1(BaL) in the presence/absence of TIZ or RM4848. HIV-1 p24 were measured at different timepoints. The immunomodulatory abilities of TZD were evaluated by the expression of type I IFN pathway genes and the production of cytokines and chemokines. TZD drastically inhibited in vitro HIV-1 replication (>87%). This was associated with the activation of innate immune responses and with the up-regulation of several interferon-stimulated genes (ISGs), including those involved in cholesterol pathway, particularly the cholesterol-25 hydroxylase (CH25H). TZD inhibition of HIV-1 replication in vitro could be due to their ability to stimulate potent and multifaceted antiviral immune responses. These data warrant the exploration of TZD as preventive/therapeutic agent in HIV infection.
Thiazolides elicit anti-viral innate immunity and reduce HIV replication / D. Trabattoni, F. Gnudi, S. Ibba, I. Saulle, S. Agostini, M. Masetti, M. Biasin, J. Rossignol, M. Clerici. - In: SCIENTIFIC REPORTS. - ISSN 2045-2322. - 6(2016 Jun 02), pp. 27148.1-27148.10.
|Titolo:||Thiazolides elicit anti-viral innate immunity and reduce HIV replication|
TRABATTONI, DARIA LUCIA (Primo)
GNUDI, FEDERICA (Secondo)
CLERICI, MARIO SALVATORE (Corresponding)
|Parole Chiave:||C virus-replication; hepatitis-B-virus; seronegative individuals; protein-kinase; double-blind; viral entry; nitazoxanide; inhibition; infection; receptor|
|Settore Scientifico Disciplinare:||Settore MED/04 - Patologia Generale|
|Data di pubblicazione:||2-giu-2016|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1038/srep27148|
|Appare nelle tipologie:||01 - Articolo su periodico|