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Journal of Virology, October 2009, p. 10494-10503, Vol. 83, No. 20
0022-538X/09/$08.00+0     doi:10.1128/JVI.00928-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Biological Signature Characteristics of Primary Isolates from Human Immunodeficiency Virus Type 1 Group O in Ex Vivo Human Tonsil Histocultures{triangledown}

Silvia Geuenich,1 Lars Kaderali,2 Ina Allespach,1 Serkan Sertel,3 and Oliver T. Keppler1*

Department of Virology,1 ViroQuant Research Group Modeling, Bioquant,2 Department of Otolaryngology, Head and Neck Surgery, University of Heidelberg, Heidelberg, Germany3

Received 9 May 2009/ Accepted 30 July 2009

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.

* Corresponding author. Mailing address: Department of Virology, University of Heidelberg, Im Neuenheimer Feld 324, D-69120 Heidelberg, Germany. Phone: 49 6221 565007. Fax: 49 6221 565003. E-mail: oliver_keppler{at}med.uni-heidelberg.de

{triangledown} Published ahead of print on 12 August 2009.

Journal of Virology, October 2009, p. 10494-10503, Vol. 83, No. 20
0022-538X/09/$08.00+0     doi:10.1128/JVI.00928-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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