title: Characterization of alpha-defensins plasma levels in Macaca fascicularis and correlations with virological parameters during SHIV89.6Pcy11 experimental infection.
abstract: Alpha-defensins have been shown to inhibit HIV-1 replication in vitro and may contribute to the overall control of viral replication in vivo. In the present work, we quantitatively measured the levels of alpha-defensins in the plasma of healthy and experimentally SHIV-infected Macaca fascicularis (cynomolgus monkeys), an animal model of AIDS pathogenesis and vaccine development. Characterization of physiological plasma alpha-defensins levels was performed in 12 healthy monkeys following longitudinal analysis using an alpha-defensins ELISA kit currently validated for macaque use. Subsequently, alpha-defensins levels were quantitatively measured in 23 cynomolgus monkeys during titration protocols following both the mucosal and systemic routes of infection with the pathogenic SHIV89.6P(cy11). A significant increase in plasma alpha-defensins levels was consistently observed at early time points in all infected animals, regardless of the infection route. Moreover, a positive correlation was observed between viral replication and levels of alpha-defensins during the acute phase of infection. Interestingly, in the animals infected through the mucosal route, alpha-defensins levels remained significantly higher at later time points, up to 19 weeks from the infection, while in cynomolgus infected intravenously, alpha-defensins levels returned to baseline levels by 4 weeks from infection, suggesting that the different route of infection may differently activate the innate immune response.
authors.affiliation: Department of Drug Research and Evaluation, National AIDS Center, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy. baroncel@iss.it
authors.forename: Silvia
authors.initials: S
authors.lastname: Baroncelli
authors.forename: Donatella R M
authors.initials: DR
authors.lastname: Negri
authors.forename: Claudia
authors.initials: C
authors.lastname: Rovetto
authors.forename: Roberto
authors.initials: R
authors.lastname: Belli
authors.forename: Massimo
authors.initials: M
authors.lastname: Ciccozzi
authors.forename: Stefania
authors.initials: S
authors.lastname: Catone
authors.forename: Zuleika
authors.initials: Z
authors.lastname: Michelini
authors.forename: Martina
authors.initials: M
authors.lastname: Borghi
authors.forename: Pasqualina
authors.initials: P
authors.lastname: Leone
authors.forename: Zahra
authors.initials: Z
authors.lastname: Fagrouch
authors.forename: Jonathan
authors.initials: J
authors.lastname: Heeney
authors.forename: Andrea
authors.initials: A
authors.lastname: Cara
mesh_terms: D000285:Administration, Rectal; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006678:HIV / Q000276:immunology; D007262:Infusions, Intravenous; D008252:Macaca fascicularis / Q000276:immunology / Q000821:virology*; D008297:Male; D016097:Simian Acquired Immunodeficiency Syndrome / Q000097:blood / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology* / Q000472:pathogenicity; D014766:Viremia; D014779:Virus Replication; D023084:alpha-Defensins / Q000097:blood*
chemical_list: D023084:alpha-Defensins