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Journal of Virology, December 2008, p. 11526-11535, Vol. 82, No. 23
0022-538X/08/$08.00+0     doi:10.1128/JVI.01111-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Excretion of Human Immunodeficiency Virus Type 1 through Polarized Epithelium by Immunoglobulin A{triangledown}

Alison Wright,1 Michael E. Lamm,1 and Yung T. Huang1,2*

Institute of Pathology, Case Western Reserve University,1 University Hospitals Case Medical Center, Cleveland, Ohio 441062

Received 26 May 2008/ Accepted 22 September 2008

Human immunodeficiency virus (HIV) is transmitted primarily sexually across mucosal surfaces. After infection, HIV propagates initially in the lamina propria below the polarized epithelium and causes extensive destruction of mucosal T cells. Immunoglobulin A (IgA) antibodies, produced in the lamina propria and then transcytosed across the mucosal epithelium into the lumen, can be the first line of immune defense against HIV. Here, we used IgA monoclonal antibodies against HIV envelope proteins to investigate the abilities of polarized primate and human epithelial cells to excrete HIV virions from the basolateral to the apical surface via polymeric Ig receptor (pIgR)-mediated binding and the internalization of HIV-IgA immune complexes. African green monkey kidney cells expressing pIgR demonstrated HIV excretion that was dependent on the IgA concentration and the exposure time. Matched IgG antibodies with the same variable regions as the IgA antibodies and IgA antibodies to non-HIV antigens had no HIV excretory function. A mixture of two IgA anti-bodies against gp120 and gp41 showed a synergistic increase in the level of HIV excreted. The capacity for HIV excretion correlated with the ability of IgA antibodies to bind HIV and of the resulting immune complexes to bind pIgR. Consistent with the epithelial transcytosis of HIV-IgA immune complexes, the colocalization of HIV proteins and HIV-specific IgA was detected intracellularly by confocal microscopy. Our results suggest the potential of IgA antibodies to excrete HIV from mucosal lamina propria, thereby decreasing the viral burden, access to susceptible cells, and the chronic activation of the immune system.

* Corresponding author. Mailing address: Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106. Phone: (216) 844-8611. Fax: (216) 368-0495. E-mail: yth{at}case.edu

{triangledown} Published ahead of print on 1 October 2008.

Journal of Virology, December 2008, p. 11526-11535, Vol. 82, No. 23
0022-538X/08/$08.00+0     doi:10.1128/JVI.01111-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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