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Journal of Virology, November 1998, p. 8650-8658, Vol. 72, No. 11
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Potential Contributions of Viral Envelope and Host Genetic Factors in a Human Immunodeficiency Virus Type 1-Infected Long-Term Survivor

Kathie Grovit-Ferbas,1,2 John Ferbas,1,2 Vaheideh Gudeman,1,3 Saeed Sadeghi,2 Matthew Bidwell Goetz,1,2 Janis V. Giorgi,1 Irvin S. Y. Chen,1,3,* and William A. O'Brien1,2,dagger

Division of Hematology-Oncology, Department of Medicine1 and Department of Microbiology and Immunology,3 UCLA School of Medicine and UCLA AIDS Institute, Los Angeles, California 90095-1678, and VA Medical Center, Los Angeles, California 900732

Received 1 April 1998/Accepted 20 July 1998

The lack of clinical progression in some individuals despite prolonged human immunodeficiency virus type 1 (HIV-1) infection may result from infection with less-pathogenic viral strains. To address this question, we examined the HIV-1 envelope protein from a donor with a low viral burden, stable CD4+ T-lymphocyte counts, and little evidence of CD8+ T-cell expansion, activation, or immune activity. To avoid potential changes in envelope function resulting from selection in vitro, envelope clones were constructed by using viral RNA isolated from uncultured peripheral blood mononuclear cells (PBMC). The data showed that recombinant viruses containing envelope sequences derived from RNA isolated from patient PBMC replicated poorly in primary CD4+ T cells but demonstrated efficient growth in macrophages. The unusual phenotype of these viruses could not be explained solely by differential utilization of coreceptors since the chimeric viruses, as well as an uncloned isolate obtained from the same visit date, can utilize CCR5. In addition, the donor's own cells appeared resistant to infection with chimeric viruses containing autologous envelope sequences. Genotype analysis revealed that the donor was heterozygous for the previously described 32-bp deletion in CCR5 which may be linked with prolonged survival in HIV-1-infected individuals. These data suggest that the changes in envelope sequences confer properties of viral attenuation, which together with the CCR5 +/Delta 32 genotype could account for the long-term survival of this patient.

* Corresponding author. Mailing address: 11-934 Factor, Department of Medicine, UCLA School of Medicine and the UCLA AIDS Institute, Los Angeles, CA 90095-1678. Phone: (310) 825-4793; Fax: (310) 794-7682. E-mail: rtaweesu{at}ucla.edu.

dagger Present address: University of Texas Medical Branch, Galveston, TX 77555.

Journal of Virology, November 1998, p. 8650-8658, Vol. 72, No. 11
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Poon, B., Hsu, J. F., Gudeman, V., Chen, I. S. Y., Grovit-Ferbas, K. (2005). Formaldehyde-Treated, Heat-Inactivated Virions with Increased Human Immunodeficiency Virus Type 1 Env Can Be Used To Induce High-Titer Neutralizing Antibody Responses. J. Virol. 79: 10210-10217 [Abstract] [Full Text]  
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