A Pilot Study of the Humoral Response Against the AntiSense Protein (ASP) in HIV-1-Infected Patients

Juliette Savoret (1) , Nathalie Chazal (1) , Jean-Pierre Moles (2) , Edouard Tuaillon (3, 2) , Faroudy Boufassa (4) , Laurence Meyer (4) , Camille Lecuroux (5) , Olivier Lambotte (6) , Philippe van de Perre (2) , Jean-Michel Mesnard (7) , Antoine Gross (1)

1 IRIM - Institut de Recherche en Infectiologie de Montpellier
2 Pathogénèse et contrôle des infections chroniques (PCCI)
3 CHU Montpellier
4 CESP - Centre de recherche en épidémiologie et santé des populations
5 Régulation de la réponse immune, infection VIH-1 et autoimmunité
6 IMVA-HB - Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes
7 CPBS - Centre d’études d’Agents Pathogènes et Biotechologies pour la Santé

The existence of an antisense Open Reading Frame (ORF) that encodes a putative AntiSense Protein (ASP) on the proviral genome of Human Immunodeficiency Virus type 1 (HIV-1) was a source of debate for 30 years. During the last years, some progresses have been made to characterize the cellular immune response against ASP in HIV-1 seropositive patients. However, no tools were available for the detection of antibodies to ASP in the plasma of HIV-1-infected patients during the natural course of the infection. The aim of our study was to develop a Luciferase Immuno-Precipitation System (LIPS) to monitor the quantitative detection of ASP-specific antibodies in the plasma of HIV-1-infected patients [antiretroviral therapy (ART) naive-patients, patients under ART and HIV-1 controllers], patients who discontinued antiretroviral drugs (ARV). We further used this approach to delineate the epitopes of ASP targeted by antibodies. Antibodies directed against ASP were detected in 3 out of 19 patients who discontinued ARV (15%) and in 1 out of 10 ART-naive patients (10%), but were neither detected in HIV-1 infected patients under ART nor in HIV-1 controllers. Individual variations in levels of ASP-specific antibodies were detected overtime. Both the conserved prolin-rich motif and the core 60–189 region of ASP were found to be essential for antibody recognition in the four patients tested positive for anti-ASP antibodies, who were all untreated at the time of sampling. Moreover, for two of these patients, increased levels of ASP-specific antibodies were observed concomitantly to viremia declines. Overall, our method may represent a useful tool to detect a humoral response to ASP in HIV-1-infected patients, which allowed us to confirm the expression of ASP during the course of HIV-1 infection. Further studies will be needed to fully characterize the humoral response to ASP in HIV-1-infected patients.

Mots clés: HIV-1; antisense protein; antibodies; luciferase immuno-precipitation system; viremia

Domaines: Immunité adaptative; Maladies infectieuses

Juliette Savoret, Nathalie Chazal, Jean-Pierre Moles, Edouard Tuaillon, Faroudy Boufassa, et al.. A Pilot Study of the Humoral Response Against the AntiSense Protein (ASP) in HIV-1-Infected Patients. Frontiers in Microbiology, 2020, 11, pp.20. ⟨10.3389/fmicb.2020.00020⟩. ⟨hal-02453818⟩