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

Gray, Rebecca Ra,b; Salemi, Marcoa,b; Lowe, Amandaa; Nakamura, Kyle Jc,d; Decker, William Dc; Sinkala, Mosese; Kankasa, Chipepof; Mulligan, Connie Jg; Thea, Donald Mh; Kuhn, Louisei; Aldrovandi, Gracec,d,*; Goodenow, Maureen Ma,j,*

doi: 10.1097/QAD.0b013e328340fdaf
Basic Science

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: goodenow@pathology.ufl.edu

© 2011 Lippincott Williams & Wilkins, Inc.