Differences in the fitness of two diverse wild-type human immunodeficiency virus type 1 isolates are related to the efficiency of cell binding and entry.
The ability of one primary human immunodeficiency virus type 1 (HIV-1) isolate to outcompete another in primary CD4+ human lymphoid cells appears to be mediated by the efficiency of host cell entry. This study was designed to test the role of entry on fitness of wild-type HIV-1 isolates (e.g., replicative capacity) and to examine the mechanism(s) involved in differential entry efficiency. The gp120 coding regions of two diverse HIV-1 isolates (the more-fit subtype B strain, B5-91US056, and less-fit C strain, C5-97ZA003) were cloned into a neutral HIV-1 backbone by using a recently described yeast cloning technique. The fitness of the primary B5 HIV-1 isolates and its env gene cloned into the NL4-3 laboratory strain had similar fitness, and both were more fit than the C5 primary isolate and its env/NL4-3 chimeric counterpart. Increased fitness of the B5 over C5 virus was mediated by the gp120 coding region of the env gene. An increase in binding/fusion, as well as decreased sensitivity to entry inhibitors (PSC-RANTES and T-20), was observed in cell fusion assays mediated by B5 gp120 compared to C5 gp120. Competitive binding assays using a novel whole virus-cell system indicate that the primary or chimeric B5 had a higher avidity for CD4/CCR5 on host cells than the C5 counterpart. This increased avidity of an HIV-1 isolate for its cell receptors may be a significant factor influencing overall replicative capacity or fitness.
Marozsan
Andre J
AJ
Division of Infectious Diseases, Department of Medicine, Case Western Reserve University, 10900 Euclid Ave., Cleveland, OH 44106, USA.
Moore
Dawn M
DM
Lobritz
Michael A
MA
Fraundorf
Erika
E
Abraha
Awet
A
Reeves
Jacqueline D
JD
Arts
Eric J
EJ
D001483:Base Sequence; D001667:Binding, Competitive; D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D002678:Chimera / Q000235:genetics; D004279:DNA, Viral / Q000235:genetics; D015870:Gene Expression; D005814:Genes, Viral; D015752:Genes, env; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000502:physiology; D015497:HIV-1 / Q000145:classification / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D008561:Membrane Fusion / Q000502:physiology; D008969:Molecular Sequence Data; D015728:Receptors, HIV / Q000235:genetics / Q000502:physiology; D012689:Sequence Homology, Nucleic Acid; D013045:Species Specificity; D014774:Virulence / Q000235:genetics / Q000502:physiology
D004279:DNA, Viral; D015699:HIV Envelope Protein gp120; D015728:Receptors, HIV