14th International AIDS Conference Barcelona, Spain — July 7-12, 2002

Int Conf AIDS. 2002 Jul 7-12;14:Abstract No. A10003

BACKGROUND: Primary HIV-1 isolates can be subdivided into two groups according to their biological phenotype. Fast replication to high titers and syncytium formation in peripheral blood mononuclear cells (PBMC) and the capacity to infect and replicate in a broad range of T-lymphoid and monocytoid cell lines often characterise viruses isolated from immunodeficient patients. In contrast, slow replication to low titers and induction of small, if any, syncytia in PBMC are characteristic of viruses isolated from individuals with no or mild symptoms of HIV infection. These viruses lack the capacity to infect and replicate in established cell lines. The two groups have been classified as rapid/high or syncytium-inducing (SI) and slow/low or non-syncytium-inducing (NSI) isolates. Shown in a Kaplan-Meyer plot the survival time of SI carriers is significantly shorter.

The third variable region (V3) of the viral envelope protein gp120 plays a major role in the interaction of the viral envelope with the coreceptors and the development of the described biological phenotypes. It is unclear whether other HIV genes are also involved in the different cytopathic effects and replicative capacities.

METHODS: We analysed sequence variations in the V3 loop of gp120 as well as in the accessory genes and their correlation with the different phenotypes in terms of mutual information, an entropy-based correlation measure. We calculated the mutual information of gp120-V3, vpu, vpr and vif to evaluate the statistical significance of each sequence position in the accessory genes for cytopathogenicity.

RESULTS AND CONCLUSIONS: We did not only find the expected strong correlation between amino acid composition of the V3 region and the different in vitro phenotypes, but also a significant correlation between vpu sequences and the SI and NSI phenotype. Variations in vif and vpr sequences did not show any such correlation suggesting a role in the cytopathic effect for both gp120 and vpu.

Presenting author: Rolf Kaiser

1Institut fuer Virologie der Universitaetsklinik, Koeln, Germany.

2Max-Planck-Institut fuer Informatik, Saarbruecken, Germany.

3Institut fuer Medizinische Mikrobiologie der Universitaetsklinik, Bonn, Germany.

4Fraunhofer Institut fuer Algorithmen und Wissenschaftliches Rechnen, Sankt Augustin, Germany.

5Forschungszentrum caesar, Bonn, Germany.

6Insitut fuer Medizinische Mikrobiologie der Universitaetsklinik, Bonn, Germany.

7Medizinische Klinik I der Universitaetsklinik, Bonn, Germany.

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