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Session 38
Poster Session
Viral and Cellular Proteins on the Virion Surface Session Time: 4:30-6:30 pm Room 4E-F |
Methods: We have recently established a dual virus competition assay to measure the relative fitness of any 2 HIV-1 isolates ex vivo. This assay involves a heteroduplex tracking technique or real-time PCR to calculate and then compare the relative fitness of each HIV-1 isolate in a competition. Results: Dominance of subtype C in the worldwide epidemic suggests that this subtype may be more fit other subtypes. To test this hypothesis, we have performed competitions between 6 subtype C and 9 subtype B NSI/R5 HIV-1 isolates in PBMC. All subtype C isolates were out-competed by subtype B isolates in pair-wise competitions (p < 0.0001). However, fitness differences between HIV-1 isolates of the same subtype were not significant. Preliminary results now suggest that subtype C isolates may also be less fit than subtype A and D isolates. The fitness differences between the B and C isolates could also be used to construct pair-wise matrices and phylogenetic trees using the neighbor-joining method. Phylogenetic trees based on fitness difference between subtype B and C isolates were similar to those based on genetic distances between envelope genes. Interestingly, HIV-1 isolates appear to compete at the level of HIV-1 entry and not during other steps in the replication. Conclusions: Subtype C isolates are less fit than isolates of other subtypes. This fitness difference maps to the env gene and is controlled by the efficiency of host cell entry. Thus, a decrease in pathogenicity (i.e. ex vivo fitness) coupled with increased survival of a subtype C-infected individual could increase the likelihood of subtype C transmission and prevalence in the human population (i.e. in vivo fitness). |
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©2002 9th Conference on Retroviruses and Opportunistic Infections |
