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Relationship between V3 genotype, biologic phenotype, tropism, and coreceptor use for primary isolates of human
R A McDonald1, G Chang, N L Michael
1Department of Molecular Diagnostic and Pathogenesis, Division of Retrovirology, Walter Reed Army Institute of Research, Rockville, Maryland 20850, USA.
Objectives:
The predictive value of positively charged amino acids at positions 11 and 25 within the V3 loop region of the human immunodeficiency virus type 1 (HIV-1) envelope gene for the syncytium-inducing (SI) phenotype was assessed.
Study Design/Methods:
Sequencing was performed on DNA extracted from primary peripheral blood mononuclear cells (PBMCs) and complementary DNA (cDNA) prepared from serial viral isolates from 10 HIV-1-seropositive subjects. Proviral DNA sequencing was also performed on biologic clones from most of these subjects.
Results:
Positive charge at position 11 and/or 25 in 257 isolate cDNA, PBMC DNA, and biologic clone PBMC DNA sequences was compared with 69 phenotypic determinations, of which 62.3% were SI. V3 genotype was 51.2% sensitive and 85.8% specific for the SI phenotype, with positive and negative predictive values of 62.8% and 79.0%, respectively. Cellular tropism failed to correlate with V3 genotype, coreceptor use, or biologic phenotype. Exclusive use of CCR5 was associated with the nonsyncytium-inducing (NSI) phenotype. Overall, V3 loop charge was higher in SI than in NSI isolates (5.01 and 3.78, respectively; p = 0.0211).
Conclusions:
The predictive power of SI phenotype from V3 genotype is relatively weak, especially in a low SI prevalence population. The direct measurement of viral phenotype, cellular tropism, and coreceptor use in HIV-1 isolates is essential for accurate biologic characterization.