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Journal of Virology, April 2006, p. 3721-3731, Vol. 80, No. 8
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.8.3721-3731.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Genetic Analysis of Simian Immunodeficiency Virus Expressed in Milk and Selectively Transmitted through Breastfeeding

Jenna Rychert, Nedra Lacour, and Angela Martin Amedee*

Department of Microbiology, Immunology, Parasitology, Louisiana State University Health Sciences Center, 1901 Perdido St., New Orleans, Louisiana 70112

Received 18 April 2005/ Accepted 31 January 2006

To develop effective intervention strategies that prevent breast milk transmission of human immunodeficiency virus (HIV), we must understand the specific viral properties and mechanisms responsible for infant infection. We have used lactating rhesus macaques infected with a pathogenic simian immunodeficiency virus (SIV) stock to analyze the viral genotypes expressed in plasma and milk throughout the disease course and to identify those variants ultimately transmitted to infants through breastfeeding. In these studies we observed mother-to-infant transmission of SIV/DeltaB670 by eight females during the chronic phase of disease, and we analyzed by heteroduplex tracking assays and sequence analysis the distribution and fluctuations in viral genotypes expressed. Each female expressed multiple V1 envelope genotypes in milk near the time of transmission, while a single genotype was found in each of the infants. Variants transmitted to infants were not expressed throughout the maternal disease course but were only detected near the time of transmission. The emergence of the transmitted genotype in the dam typically occurred in plasma before milk and was coincident with increased milk viral loads. Transmitted genotypes tended to be longer and more glycosylated and had a less negative charge over the V1 region compared to viral genotypes expressed in milk but not transmitted. These observations demonstrate that specific viral genotypes are selectively transmitted to infants through breastfeeding and support the hypothesis that transmission occurs as genotypes adapt for efficient expression in milk.

* Corresponding author. Mailing address: Louisiana State University Health Sciences Center, Department of Microbiology, Immunology, Parasitology, 1901 Perdido St., New Orleans, LA 70112. Phone: (504) 568-5608. Fax: (504) 568-2918. E-mail: aamede{at}lsuhsc.edu.

Journal of Virology, April 2006, p. 3721-3731, Vol. 80, No. 8
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.8.3721-3731.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.





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