PubMed · 10748537
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A Persidis. 2000. Progress against AIDS.. https://doi.org/10.1038/74566
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The Env protein of human immunodeficiency virus type 1 is assembled into a stable trimer, and oligomerization is required for maintenance of viral infectivity. This property of Env suggests that Env mutants may have a dominant-negative effect on virus infectivity. To investigate this possibility, we established a packaging cell line in which both wild-type and mutant Env proteins could be expressed simultaneously in a single cell. We analyzed the effects of two types of Env mutants: cytoplasmic tail-truncated TM mutants and a mutant defective in gp120/gp41 cleavage. The cytoplasmic tail-truncated proteins were found to be incorporated into virions by forming an oligomer with wild-type TM, but could not inhibit the wild-type function. In contrast, phenotypic mixing of cleavage-defective Env with the wild-type protein caused dramatic inhibition of infectivity, indicating that this mutant has a strong dominant-negative phenotype.
The genetic diversity of group M HIV-1 is highest in west central Africa. Blood samples from four locations in Cameroon were collected to determine the molecular epidemiology of HIV-1. The C2-V5 region of envelope was sequenced from 39 of the 40 samples collected, and 7 samples were sequenced across the genome. All strains belonged to group M of HIV-1. The circulating recombinant form CRF02 AG (IbNG) was the most common strain (22/39, 56%). Two of these were confirmed by full genome analysis. Four samples (4/39, 10%) clustered with the sub-subtype F2 and one of these was confirmed by full genome sequencing. Recombinant forms, each different but containing subtype A, accounted for the next most common form (7/39, 18%). Among these recombinants, those combining subtypes A and G were the most common (4/7, 57%). Also found were 3 subtype A, 2 subtype G, and 1 subtype B strain. Many recombination break points were shared between IbNG and the other AG recombinants, though none of these other AG recombinants included IbNG as a parent. This suggests that there was an ancestral AG recombinant that gave rise to CRF02 AG (IbNG), the successful circulating recombinant form, and to others that were less successful and are now rare.