• Medientyp: E-Artikel
  • Titel: 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
  • Beteiligte: Marozsan, Andre J.; Moore, Dawn M.; Lobritz, Michael A.; Fraundorf, Erika; Abraha, Awet; Reeves, Jacqueline D.; Arts, Eric J.
  • Erschienen: American Society for Microbiology, 2005
  • Erschienen in: Journal of Virology, 79 (2005) 11, Seite 7121-7134
  • Sprache: Englisch
  • DOI: 10.1128/jvi.79.11.7121-7134.2005
  • ISSN: 0022-538X; 1098-5514
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  • Beschreibung: ABSTRACT 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.
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