Phenotypic heterogeneity in a panel of infectious molecular human immunodeficiency virus type 1 clones derived from a single individual.
Previously, we and others have demonstrated a relation between the clinical course of human immunodeficiency virus type 1 (HIV-1) infection and biological properties of HIV-1 variants such as replication rate, syncytium-inducing (SI) capacity, and cytotropism. For the molecular analysis of the biological variability in these properties, we generated a panel of phenotypically distinct yet genetically highly homologous infectious molecular clones. These clones were derived from HIV-1 isolates, mostly recovered by direct clonal isolation, from a single individual in whom a transition from non-SI to SI isolates had been identified over time. Of 17 molecular clones tested, 8 were infectious. The clones exhibited differences in SI capacity and T-cell line tropism. Their phenotypes corresponded to those of their parental isolates, formally demonstrating that biological variability of HIV-1 isolates can be attributed to single molecular clones. With these clones we demonstrated that SI capacity and tropism for the H9 T-cell line, almost invariably coupled in primary HIV-1 isolates, are discernible properties. Also different requirements appeared to exist for H9 and Sup T1 cell line tropism. We obtained evidence that T-cell line tropism is not caused by differences in level of HIV-1 expression but most probably is restricted at the level of virus entry. Restriction mapping of four clones with divergent phenotypes revealed a high degree of nucleotide sequence homology (over 96.3%), indicating the usefulness of these clones for the tracking of genetic variability critical for differences in biological phenotype.
Groenink
M
M
Central Laboratory of The Netherlands Red Cross Blood Transfusion Service, Amsterdam.
Fouchier
R A
RA
de Goede
R E
RE
de Wolf
F
F
Gruters
R A
RA
Cuypers
H T
HT
Huisman
H G
HG
Tersmette
M
M
D000163:Acquired Immunodeficiency Syndrome / Q000235:genetics; D000595:Amino Acid Sequence; D001483:Base Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D015756:Genes, tat; D014644:Genetic Variation; D015726:Giant Cells / Q000382:microbiology; D015497:HIV-1 / Q000235:genetics* / Q000254:growth & development; D008969:Molecular Sequence Data; D010641:Phenotype; D015183:Restriction Mapping; D012689:Sequence Homology, Nucleic Acid; D013601:T-Lymphocytes / Q000382:microbiology; D014779:Virus Replication