AEGiS-13IAC: Host cell-derived differentiation, activation and costimulatory/adhesion molecules acquired by circulating HIV-1: longitudinal analysis in patients undergoing controlled therapy interruption.

13th International AIDS Conference

Durban, South Africa - July 9-July 14, 2000

Host cell-derived differentiation, activation and costimulatory/adhesion molecules acquired by circulating HIV-1: longitudinal analysis in patients undergoing controlled therapy interruption.

Int Conf AIDS 2000 Jul 9-14; 13:(abstract no. ThOrB749)

Capobianchi MR, Abbate I, Dianzani F, Turriziani O, Antonelli G, D'Offizi G, Galati V, Pierdominici M, Pandolfi F
M. R. Capobianchi, Via Portuense 292, 00149 Rome, Italy, Italy, Tel.: +39-06-55170434, Fax: +39-06-5594555, E-mail: virology@ats.it

Aim: Nine patients were tested for the presence of cellular membrane molecules (CMPs) on the surface of circulating HIV-1, both before HAART and after controlled therapy suspension.

METHODS: Virus embedded CMPs were tested with a new, highly sensitive immunocapture method. Plasma samples were applied to immobilized Mabs and captured virus was detected by quantitative RT-PCR.

RESULTS: LFA-3 was the most represented CMP on the surface of circulating virions. CD45RO was the second most relevant molecule, while CD45RA was much less represented. HLA-DR, and, to a lesser extent, L-selectin, were detected in plasma virus from a significant proportion of patients, whereas FasL, B7-1 and B7-2 were only occasionally detected. After therapy interruption, a significant reduction of both HLA-DR and CD45RO on the surface of circulating virions was observed as compared to pre-therapy levels, whereas the remaining CMP pattern remained virtually unchanged.

CONCLUSIONS: This is the first evidence that cell-derived differentiation and activation markers, as well as costimulatory/adhesion molecules, are actually included in the envelope of HIV-1 in vivo, suggesting that circulating virus could contribute to immune dysregulation also through envelope-embedded CMPs. This aproach prompts the possibility to directly analyze the cellular source of HIV-1 circulating in vivo. To this respect, the predominance of CD45RO over CD45RA supports that memory, and not naive, T cells are the actual main source of circulating HIV-1, at least in the asymptomatic stages. The changes observed in the pattern of CMP embedded by replicating HIV-1 after theraphy discontinuation can help to identify viral reservoirs responsible for rapid virus rebound following therapy interruption.

Keywords: AEGIS, HIV-1, Antiretroviral Therapy, Highly Active, Cell Adhesion Molecules, Antigens, CD45, Virion, Cell Differentiation, Antigens, CD58, HLA-DR Antigens, Human, therapy, analysis, immunology, drug therapy
000709
ThOrB749