Multiple independent lineages of HIV-1 persist in breast milk and plasma

Abstract

Design-The origin and evolution of HIV-1 in breast milk is unclear, despite the continuing significance of this tissue as a transmitting compartment. To elucidate the evolutionary trajectory of viral populations in a transient mucosal compartment, longitudinal sequences of the envelope gp120 region from plasma and breast milk spanning the first year after delivery were analyzed in six women infected by HIV-1 subtype C.Methods-Multiple phylogenetic algorithms were used to elucidate the evolutionary history and spatial structure of virus populations between tissues.Results-Overall persistent mixing of viral sequences between plasma and breast milk indicated that breast milk is not a distinct genetic viral compartment. Unexpectedly, longitudinal phylogenies showed multiple lineages defined by long branches that included virus from both the breast milk and the plasma. Plasma was unlikely the anatomical origin of the most recent common ancestor (MRCA) in at least three of the subjects, while in other women, the temporal origin of the MRCA of the viral populations following delivery occurred well before the onset of breast milk production.Corresponding Author: Maureen M. Goodenow 2033 Mowry Road PO Box 103633 Gainesville, Fl, 32610-3633. * These authors contributed equally to the manuscript. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Conclusions-These findings suggest that during pregnancy/lactation, a viral variant distinct from the plasma virus initially seeds the breast milk, followed by subsequent gene flow between the plasma and breast milk tissues. This study indicates the potential for reactivation or reintroduction of distinct lineages during major immunological disruptions during the course of natural infection. NIH Public Access

Immunology of pediatric HIV infection

“…Interestingly, this viral restriction is quantitative not qualitative. The HIV variants that enter breast milk are genetically indistinguishable from those in contemporaneous plasma (36,(42)(43)(44). Within breast milk, there is limited viral evolution, which may reflect restricted replication (36,43,45).…”

The Breadth and Potency of Passively Acquired Human Immunodeficiency Virus Type 1-Specific Neutralizing Antibodies Do Not Correlate with the Risk of Infant Infection

“…Recent studies indicate that the viruses in breast milk and blood are intermingled and are not generally compartmentalized (15,17), suggesting that breast milk viruses are typical of circulating viruses. Moreover, the probability of infection per exposure during breastfeeding, measured either as per liter of breast milk ingested or by daily exposure, is generally similar to the probability of infection from one unprotected exposure during sexual transmission (38).…”

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