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Isolation of primary HIV-1 that target CD8+ T Lymphocytes using CD8 as a receptor

Nature Medicine volume 7, pages 65–72 (2001)Cite this article

An Erratum to this article was published on 01 February 2001

Abstract

HIV-1 use CD4 receptors to infect their primary targets, CD4+ cells, whereas CD8+ cells have a protective role against HIV-1. We recently isolated HIV-1-producing CD8+ clones from two AIDS patients. Here we show that although HIV-1 produced by CD8+ cells maintained the ability to infect CD4+ cells, these viruses were able to infect CD8+ cells independent of CD4. Evidence indicates that these viruses used CD8 as a receptor to infect CD8+ cells. First, expression of CD8 was downmodulated after infection. Second, anti-CD8 antibodies blocked viral entry and replication in CD8+ cells. Finally, resistant cells became susceptible after expression of CD8. Although these viruses used CXCR4 to enter CD4+ cells, it seems that infection of CD8+ cells was independent of CXCR4 or CCR5 co-receptors. Novel changes were observed in envelope sequences of CD8-tropic viruses. These results provide initial evidence that HIV-1 can mutate to infect CD8+ cells using CD8 as a receptor.

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Figure 1: a and b, Infection of PBL, purified CD8+ and CD4+ cells with AD3.v6 (a) and AD3.v22 (b) viruses.
Figure 2: a, Expression of CD8, CD4 and HIV-1 mRNA in CD8+/CD4− population.
Figure 3: a, Infection of KRCD8 cells by AD3.v6 and AD3.v22 viruses.
Figure 4: a, Infection of HeLa T8+ cells with AD3.v6 and AD3.v22 viruses.
Figure 5: (a) Blocking of entry of AD3.v6 and AD3.v22 viruses into KRCD8 cells by anti-CD8 antibodies.
Figure 6: a and b, Inhibition of infection of CD8+ cells with AD3.v6 and AD3.v22 viruses by anti-CD8 antibodies.
Figure 7: Sequence analysis of envelopes of AD3.v6 and AD3.v22 viruses in comparison to HXB2 and WEAU1.6, closest matched isolate to AD3.v6 and AD3.v22 viruses.

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Acknowledgements

We thank P.R. Johnson, C.M. Walker, J.I. Mullins, A. van' Wout, P. Gupta, B. Graham and J. Zack for helpful suggestions and critical review of the manuscript; R. Munson for advice for sequencing; K. Howe for help with the phylogenetic analyses; C. McAllister for assistance with flow cytometry; A. Dutcher for support in manuscript preparation; and the Children's Research Institute (Columbus) for support. This work was supported by two grants from NIH (AI-42715 and AI-44974) and a grant from the American Foundation for AIDS Research (AMFAR) to K.S.

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Authors and Affiliations

  1. Division of Molecular Medicine, Department of Pediatrics, Immunology and Medical Genetics, Children's Research Institute and The Ohio State University Medical Center, Columbus, 43205, Ohio, USA

    Kunal Saha, Jianchao Zhang, Anil Gupta, Rajnish Dave, Meron Yimen & Bouchra Zerhouni

  2. Department of Molecular Virology, Immunology and Medical Genetics, Children's Research Institute and The Ohio State University Medical Center, Columbus, 43205, Ohio, USA

    Kunal Saha

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Correspondence to Kunal Saha.

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Saha, K., Zhang, J., Gupta, A. et al. Isolation of primary HIV-1 that target CD8+ T Lymphocytes using CD8 as a receptor. Nat Med 7, 65–72 (2001). https://doi.org/10.1038/83365

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