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.
aDepartment of Pathology, Immunology and Laboratory Medicine, USA
bEmerging Pathogens Institute, University of Florida, Gainesville, Florida, USA
cChildren's Hospital of Los Angeles, USA
dUSC Keck School of Medicine, Los Angeles, California, USA
eLusaka District Health Management Team, Zambia
fUniversity Teaching Hospital, University of Zambia, Lusaka, Zambia
gDepartment of Anthropology, University of Florida, Gainesville, Florida, USA
hBoston University School of Public Health, Boston, Massachusetts, USA
iColumbia University, New York, New York, USA
jFlorida Center for AIDS Research, University of Florida, Gainesville, Florida, USA.
*G.A. and M.M.G. contributed equally to the writing of the manuscript.
Received 30 June, 2010
Revised 23 September, 2010
Accepted 27 September, 2010
Correspondence to Maureen M. Goodenow, PhD, 2033 Mowry Road, PO Box 103633, Gainesville, FL 32610-3633, USA. E-mail: firstname.lastname@example.org