Macrophage Tropism and Cytopathicity of HIV-1 Variants Isolated Sequentially from a Long-Term Survivor Infected with nef-Deleted Virus

Paul R Gorry*, 1, 2, 3, Dale A McPhee3, 4, 5, Steven L Wesselingh1, 2, 3, Melissa J Churchill1
1 Macfarlane Burnet Institute for Medical Research and Public Health, Melbourne, Victoria, Australia
2 Department of Medicine, Monash University, Melbourne, Victoria, Australia
3 Department of Microbiology and Immunology, University of Melbourne, Melbourne, Victoria, Australia
4 National Serology Reference Laboratory, Fitzroy, Victoria, Australia
5 St. Vincent’s Institute, Fitzroy, Victoria, Australia

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2007 Bentham Science Publishers Ltd

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestrictive use, distribution, and reproduction in any medium, provided the original work is properly cited.

* Address correspondence to this author at the Macfarlane Burnet Institute for Medical Research and Public Health, G.P.O. Box 2284, Melbourne 3001, Victoria, Australia; Tel: +61-3-9282-2129; Fax: +61-3-9282-2100; E-mail:


Long-term survival of human immunodeficiency virus type 1 (HIV-1) infection has been noted in rare cohorts of individuals infected with nef-deleted virus. Enhanced macrophage tropism and cytopathicity contribute to pathogenicity of wild type HIV-1. To better understand the pathogenesis of nef-deleted HIV-1, we analyzed the replication capacity and macrophage cytopathicity of nef-deleted HIV-1 isolated sequentially from a long-term survivor during progression to AIDS (n=6 isolates). Compared with controls, all nef-deleted viruses replicated to low levels in peripheral blood mononu-clear cells and monocyte-derived macrophages (MDM). One nef-deleted virus that was isolated on the development of AIDS caused high levels of syncytia in MDM similar to control viruses, but five viruses isolated from earlier times prior to AIDS onset caused only minimal cytopathicity. Together, these results suggest that enhanced cytopathicity of nef-deleted HIV-1 for MDM can occur independently of replication capacity, and may contribute to the pathogenesis of nef-deleted HIV-1 infection.