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Journal of Virology, August 2008, p. 7932-7941, Vol. 82, No. 16
0022-538X/08/$08.00+0     doi:10.1128/JVI.00757-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Autologous Neutralizing Humoral Immunity and Evolution of the Viral Envelope in the Course of Subtype B Human Immunodeficiency Virus Type 1 Infection {triangledown} ,{dagger}

Evelien M. Bunnik, Linaida Pisas, Ad C. van Nuenen, and Hanneke Schuitemaker*

Department of Experimental Immunology, Sanquin Research, Landsteiner Laboratory and Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands

Received 6 April 2008/ Accepted 27 May 2008

Most human immunodeficiency virus type 1 (HIV-1)-infected individuals develop an HIV-specific neutralizing antibody (NAb) response that selects for escape variants of the virus. Here, we studied autologous NAb responses in five typical CCR5-using progressors in relation to viral NAb escape and molecular changes in the viral envelope (Env) in the period from seroconversion until after AIDS diagnosis. In sera from three patients, high-titer neutralizing activity was observed against the earliest autologous virus variants, followed by declining humoral immune responses against subsequent viral escape variants. Autologous neutralizing activity was undetectable in sera from two patients. Patients with high-titer neutralizing activity in serum showed the strongest positive selection pressure on Env early in infection. In the initial phase of infection, gp160 length and the number of potential N-linked glycosylation sites (PNGS) increased in viruses from all patients. Over the course of infection, positive selection pressure declined as the NAb response subsided, coinciding with reversions of changes in gp160 length and the number of PNGS. A number of identical amino acid changes were observed over the course of infection in the viral quasispecies of different patients. Our results indicate that although neutralizing autologous humoral immunity may have a limited effect on the disease course, it is an important selection pressure in virus evolution early in infection, while declining HIV-specific humoral immunity in later stages may coincide with reversion of NAb-driven changes in Env.

* Corresponding author. Mailing address: Department of Experimental Immunology at M01-120, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. Phone: 31-20-5668298. Fax: 31-20-5669756. E-mail: h.schuitemaker{at}amc.uva.nl

{triangledown} Published ahead of print on 4 June 2008.

{dagger} Supplemental material for this article may be found at http://jvi.asm.org/.

Journal of Virology, August 2008, p. 7932-7941, Vol. 82, No. 16
0022-538X/08/$08.00+0     doi:10.1128/JVI.00757-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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