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 glycoprotein (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 patients, although in other women, the temporal origin of the MRCA of the viral populations following delivery occurred well before the onset of breast milk production. 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.