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Journal of Virology, January 2006, p. 835-844, Vol. 80, No. 2
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.2.835-844.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Neutralization Escape Variants of Human Immunodeficiency Virus Type 1 Are Transmitted from Mother to Infant

Xueling Wu,1 Adam B. Parast,1 Barbra A. Richardson,2,3 Ruth Nduati,5 Grace John-Stewart,4 Dorothy Mbori-Ngacha,5 Stephanie M. J. Rainwater,1 and Julie Overbaugh1,2*

Divisions of Human Biology,1 Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109;,2 Departments of Biostatistics,3 Medicine, University of Washington, Seattle, Washington 98104,4 Department of Pediatrics, University of Nairobi, Nairobi, Kenya5

Received 20 September 2005/ Accepted 20 October 2005

Maternal passive immunity typically plays a critical role in protecting infants from new infections; however, the specific contribution of neutralizing antibodies in limiting mother-to-child transmission of human immunodeficiency virus type 1 is unclear. By examining cloned envelope variants from 12 transmission pairs, we found that vertically transmitted variants were more resistant to neutralization by maternal plasma than were maternal viral variants near the time of transmission. The vertically transmitted envelope variants were poorly neutralized by monoclonal antibodies biz, 2G12, 2F5, and 4E10 individually or in combination. Despite the fact that the infant viruses were among the most neutralization resistant in the mother, they had relatively few glycosylation sites. Moreover, the transmitted variants elicited de novo neutralizing antibodies in the infants, indicating that they were not inherently difficult to neutralize. The neutralization resistance of vertically transmitted viruses is in contrast to the relative neutralization sensitivity of viruses sexually transmitted within discordant couples, suggesting that the antigenic properties of viruses that are favored for transmission may differ depending upon mode of transmission.

* Corresponding author. Mailing address: Division of Human Biology, Fred Hutchinson Cancer Research Center, Mail Stop C3-168, 1100 Fairview Ave. N., Seattle, WA 98109-1024. Phone: (206) 667-3524. Fax: (206) 667-1535. E-mail: joverbau{at}fhcrc.org.

Journal of Virology, January 2006, p. 835-844, Vol. 80, No. 2
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.2.835-844.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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