title: Rapid dissociation of HIV-1 from cultured cells severely limits infectivity assays, causes the inactivation ascribed to entry inhibitors, and masks the inherently high level of infectivity of virions.
abstract: By using immunofluorescence microscopy to observe and analyze freshly made HIV-1 virions adsorbed onto cells, we found that they are inherently highly infectious, rather than predominantly defective as previously suggested. Surprisingly, polycations enhance titers 20- to 30-fold by stabilizing adsorption and preventing a previously undescribed process of rapid dissociation, strongly implying that infectivity assays for many viruses are limited not only by inefficient virus diffusion onto cells but also by a postattachment race between entry and dissociation. This kinetic competition underlies inhibitory effects of CCR5 antagonists and explains why adaptive HIV-1 mutations overcome many cell entry limitations by accelerating entry.
authors.affiliation: Department of Biochemistry and Molecular Biology, Oregon Health and Science University, Portland, OR 97239-3098, USA.
authors.forename: Emily J
authors.initials: EJ
authors.lastname: Platt
authors.forename: Susan L
authors.initials: SL
authors.lastname: Kozak
authors.forename: James P
authors.initials: JP
authors.lastname: Durnin
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Hope
authors.forename: David
authors.initials: D
authors.lastname: Kabat
mesh_terms: D000327:Adsorption; D065100:CCR5 Receptor Antagonists; D002478:Cells, Cultured / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D006367:HeLa Cells; D006801:Humans; D014771:Virion / Q000378:metabolism / Q000472:pathogenicity*; D038301:Virus Inactivation; D053586:Virus Internalization
chemical_list: D065100:CCR5 Receptor Antagonists