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Human immunodeficiency virus type 1 neutralizing antibodies accelerate clearance of cell–free virions from blood plasma

Nature Medicine volume 5, pages 211–216 (1999)Cite this article

Abstract

The concentration of human immunodeficiency virus type 1 (HIV–1) particles in blood plasma is very predictive of the subsequent disease course in an infected individual; its measurement has become one of the most important parameters for monitoring clinical status1. Steady–state virus levels in plasma reflect a balance between the rates of virions entering and leaving the peripheral blood2. We analyzed the rate of virus clearance in the general circulation in rhesus macaques receiving a continuous infusion of cell–free particles in the presence and absence of virus–specific antibodies. Here we show, by measuring virion RNA, particle–associated p24 Gag protein and virus infectivity, that the clearance of physical and infectious particles from a primary, dual–tropic virus isolate, HIV–1DH12, is very rapid in naive animals, with half–lives ranging from 13 to 26 minutes. In the presence of high–titer HIV–1DH12–specific neutralizing antibodies, the half–life of virion RNA was considerably reduced (to 3.9–7.2 minutes), and infectious virus in the blood became undetectable. Although physical virus particles were eliminated extravascularly, the loss of virus infectivity in the blood reflected the combined effects of extravascular clearance and intravascular inactivation of HIV–1 infectivity due to antibody binding.

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Figure 1: a, Genomic structures of HIV–1 and SHIVs used here.
Figure 2: Clearance of physical and infectious HIV–1 particles in three naive rhesus macaques.
Figure 3: Clearance of HIV–1 in rhesus macaques persistently infected with SHIVDH12 that produce neutralizing antibodies directed against HIV–1DH12 gp120.
Figure 4: The clearance of HIV–1 is accelerated in vivo in the presence of neutralizing antibodies.
Figure 5: In vivo and ex vivo clearance of HIV–1 physical particles in blood.

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Acknowledgements

We thank G. Coleman for assistance in the animal experiments; M. Eckhaus and G. Miller for pathological analyses; C. Pierce for purification of immunoglobulin; M.G. Lewis for providing SHIV HXB2 infected monkeys; and R. Dewar for bDNA assays.

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Author notes

  1. Riri Shibata

    Present address: VaxGen, 1000 Marina Boulevard, Brisbane, California, 94005–1841, USA

Authors and Affiliations

  1. Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, 20892, Maryland, USA

    Tatsuhiko Igarashi, Charles Brown, Malcolm A. Martin & Riri Shibata

  2. Veterinary Resource Program, National Institutes of Health, Bethesda, 20892, Maryland, USA

    Ali Azadegan

  3. Seattle Biomedical Research Institute, Seattle, 98109, Washington, USA

    Nancy Haigwood

  4. Laboratory of Experimental and Computational Biology, National Cancer Institute, National Institutes of Health, Frederick, 21702, Maryland, USA

    Dimiter Dimitrov

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Igarashi, T., Brown, C., Azadegan, A. et al. Human immunodeficiency virus type 1 neutralizing antibodies accelerate clearance of cell–free virions from blood plasma. Nat Med 5, 211–216 (1999). https://doi.org/10.1038/5576

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