Relationship between V3 genotype, biologic phenotype, tropism, and coreceptor use for primary isolates of human immunodeficiency virus type 1.
OBJECTIVE
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.


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.
McDonald
R A
RA
Department of Molecular Diagnostic and Pathogenesis, Division of Retrovirology, Walter Reed Army Institute of Research, Rockville, Maryland 20850, USA.
Chang
G
G
Michael
N L
NL
D000595:Amino Acid Sequence; D005838:Genotype; D015726:Giant Cells / Q000502:physiology; D015699:HIV Envelope Protein gp120 / Q000235:genetics*; D015658:HIV Infections / Q000821:virology; D015497:HIV-1 / Q000145:classification / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D008264:Macrophages / Q000821:virology*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000235:genetics*; D010641:Phenotype; D011237:Predictive Value of Tests; D015728:Receptors, HIV / Q000378:metabolism*; D017422:Sequence Analysis, DNA; D013601:T-Lymphocytes / Q000821:virology*
D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments; D015728:Receptors, HIV