15th International HIV Drug Resistance Workshop 13-17 June 2006, Sitges, Spain

REPLICATIVE CAPACITY, SUSCEPTIBILITY TO CHEMOKINES AND TO ENTRY INHIBITORS IN SEQUENTIAL HIV VARIANTS FROM THE ACUTE AND CHRONIC PHASE OF INFECTION

Antivir Ther. 2006, 11:S45 (abstract no. 37)

V Perrin and F Mammano
INSERM U552, Hôpital Bichat-C.Bernard, Université Paris-7, Paris, France

BACKGROUND: From the virus perspective, the acute and chronic phases of infection differ for several parameters, among which target cells availability, chemokines expression and pressure from the immune system. Comparison of the envelope phenotypic characteristics of viruses from longitudinal patients' samples should reveal modifications of the selective pressure over time.

METHODS: Recombinant viruses were produced that carry envelope glycoproteins (Env) from multiple env clones obtained at the acute and chronic phases of the infection (4–6 years after), from three patients. We analysed and compared the following Env phenotypic characteristics: co-receptor use, Env replicative capacity, susceptibility to RANTES and to T-20.

RESULTS: As expected, viruses from the acute phase of the infection used exclusively CCR5 as co-receptor, and they were phenotypically (and genotypically) more homogeneous than those from the chronic phase. More interestingly, early viruses displayed significantly higher replicative capacity than viruses from the chronic phase, both in a single cycle assay and by replication in PBL. In addition, early clones were characterized by lower susceptibility to RANTES, suggesting a more efficient use of CCR5. Susceptibility to T-20 did not significantly change over time.

CONCLUSIONS: During the acute phase of infection, selection appears to favour viral variants with high replicative capacity, associated with efficient CCR5 use. Later in infection, protection from the immune response becomes a dominant selective parameter, which forces the virus into a different compromise between replicative capacity and escape.

2006-06-13
37

Copyright © 2006 - International Medical Press Ltd.. Reproduction of this abstract (other than one copy for personal reference) must be cleared through the International Medical Press Ltd. 2-4 Idol Lane, London EC3R 5DD UK.