title: Biological signature characteristics of primary isolates from human immunodeficiency virus type 1 group O in ex vivo human tonsil histocultures.
abstract: Human immunodeficiency virus type 1 (HIV-1) group M viruses have achieved a global distribution, while HIV-1 group O viruses are endemic only in particular regions of Africa. Here, we evaluated biological characteristics of group O and group M viruses in ex vivo models of HIV-1 infection. The replicative capacity and ability to induce CD4 T-cell depletion of eight group O and seven group M primary isolates were monitored in cultures of human peripheral blood mononuclear cells and tonsil explants. Comparative and longitudinal infection studies revealed HIV-1 group-specific activity patterns: CCR5-using (R5) viruses from group M varied considerably in their replicative capacity but showed similar levels of cytopathicity. In contrast, R5 isolates from group O were relatively uniform in their replicative fitness but displayed a high and unprecedented variability in their potential to deplete CD4 T cells. Two R5 group O isolates were identified that cause massive depletion of CD4 T cells, to an extent comparable to CXCR4-using viruses and not documented for any R5 isolate from group M. Intergroup comparisons found a five- to eightfold lower replicative fitness of isolates from group O than for isolates from group M yet a similar overall intrinsic pathogenicity in tonsil cultures. This study establishes biological ex vivo characteristics of HIV-1 group O primary isolates. The current findings challenge the belief that a grossly reduced replicative fitness or inherently impaired cytopathicity of viruses from this group underlies their low global prevalence.
authors.affiliation: Department of Virology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Silvia
authors.initials: S
authors.lastname: Geuenich
authors.forename: Lars
authors.initials: L
authors.lastname: Kaderali
authors.forename: Ina
authors.initials: I
authors.lastname: Allespach
authors.forename: Serkan
authors.initials: S
authors.lastname: Sertel
authors.forename: Oliver T
authors.initials: OT
authors.lastname: Keppler
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D002478:Cells, Cultured; D003588:Cytopathogenic Effect, Viral; D015497:HIV-1 / Q000145:classification* / Q000302:isolation & purification / Q000472:pathogenicity* / Q000502:physiology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology*; D008213:Lymphocyte Activation; D009924:Organ Culture Techniques; D014066:Palatine Tonsil / Q000166:cytology / Q000276:immunology / Q000821:virology*; D019713:Receptors, CCR5 / Q000378:metabolism; D014779:Virus Replication
chemical_list: D019713:Receptors, CCR5
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