Characterization of alpha-defensins plasma levels in Macaca fascicularis and correlations with virological parameters during SHIV89.6Pcy11 experimental infection.
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.
Baroncelli
Silvia
S
Department of Drug Research and Evaluation, National AIDS Center, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy. baroncel@iss.it
Negri
Donatella R M
DR
Rovetto
Claudia
C
Belli
Roberto
R
Ciccozzi
Massimo
M
Catone
Stefania
S
Michelini
Zuleika
Z
Borghi
Martina
M
Leone
Pasqualina
P
Fagrouch
Zahra
Z
Heeney
Jonathan
J
Cara
Andrea
A
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*
D023084:alpha-Defensins