AEGiS-12IAC: Genetic evolution of HIV-1 subtype A in African children presenting with a rapid or a slow disease progression.

12th International AIDS Conference

Geneva, Switzerland - June 28-July 3, 1998

Genetic evolution of HIV-1 subtype A in African children presenting with a rapid or a slow disease progression.

Int Conf AIDS 1998 Jun 28-Jul 3; 12:17 (abstract no. 11173)

Marsac D, Chaix ML, Letournevr F, Gomas E, Burgard M, Saragosti S, Rouzioux C
Laboratoire de Virologie, Hospital Necker, Paris, France.

OBJECTIVE: To study the relationship between disease outcome in perinatally infected infants and evolution of human immunodeficiency virus type 1 subtype A variants. PATIENTS: The samples were obtained from six transmitting african mothers and from their infected children selected from the French National Pediatric Cohort Study and followed up at least two years from birth. Three children had a slow development of HIV-1 infection, the three others present a severe and rapid form of the disease.

METHODS: PCR-DNA products from the maternal PBMC sample at delivery and from four sample time points per child were amplified by nested PCR and cloned; about 10 clones from each sample were sequenced encompassing the C2 through V5 regions of the viral envelope gene.

RESULTS: The infants samples showed a more homogeneous viral population (1.2 to 4.45% intrasample mean nucleotide distances) than the maternal samples (2.54 to 9.14% intrasample mean nucleotide distances). Greater genetic distances and greater branch lengths in the phylogenetic reconstructions were found for children with low virion-associated RNA burdens and slow progression to disease. Viral sequences from these children showed a tendency to form clusters that associated with different sampling times. These progressive shifts in the viral population were not found in viral sequences obtained from children who had rapid progression to disease. These children had a conserved monophyletic population of genotypic variants persisting over time. The rate of non synonymous base substitutions was higher than that of synonymous substitution in the slow progressors consistent with positive selection for change by the host immune pressure.

CONCLUSION: The increase of genetic diversity was higher in slow progressors children than in children who progressed rapidly to AIDS. The evolution of viral population is driven mainly by host immune system selective forces. The results are very close to those observed with HIV-1 subtype B virus, suggesting a similar pathogenesis for both A and B HIV-1 subtypes.

Keywords: AEGIS, HIV-1, Disease Progression, HIV Infections, Evolution, Variation (Genetics), Cohort Studies, Child, Human, Infant, genetics, ICA12
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