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Origin and evolution of HIV-1 in breast milk determined by single-genome amplification and sequencing.

dc.contributor.author Borrow, P
dc.contributor.author Center for HIV/AIDS Vaccine Immunology A0167854
dc.contributor.author Denny, Thomas Norton
dc.contributor.author Fouda, Genevieve
dc.contributor.author Hahn, Beatrice H
dc.contributor.author Kalilani, L
dc.contributor.author Kang, HH
dc.contributor.author Learn, Gerald H
dc.contributor.author Letvin, NL
dc.contributor.author Lovingood, RV
dc.contributor.author Mahlokozera, T
dc.contributor.author Meshnick, SR
dc.contributor.author Montefiori, David Charles
dc.contributor.author Permar, Sallie R
dc.contributor.author Salazar-Gonzalez, JF
dc.contributor.author Salazar, MG
dc.contributor.author Shaw, GM
dc.contributor.author Stacey, Andrea R
dc.contributor.author Wilks, AB
dc.coverage.spatial United States
dc.date.accessioned 2017-06-02T12:49:10Z
dc.date.available 2017-06-02T12:49:10Z
dc.date.issued 2011-03
dc.identifier https://www.ncbi.nlm.nih.gov/pubmed/21191008
dc.identifier JVI.02316-10
dc.identifier.uri http://hdl.handle.net/10161/14740
dc.description.abstract HIV transmission via breastfeeding accounts for a considerable proportion of infant HIV acquisition. However, the origin and evolution of the virus population in breast milk, the likely reservoir of transmitted virus variants, are not well characterized. In this study, HIV envelope (env) genes were sequenced from virus variants amplified by single-genome amplification from plasmas and milk of 12 chronically HIV-infected, lactating Malawian women. Maximum likelihood trees and statistical tests of compartmentalization revealed interspersion of plasma and milk HIV env sequences in the majority of subjects, indicating limited or no compartmentalization of milk virus variants. However, phylogenetic tree analysis further revealed monotypic virus variants that were significantly more frequent in milk (median proportion of identical viruses, 29.5%; range, 0 to 61%) than in plasma (median proportion of identical viruses, 0%; range, 0 to 26%) (P = 0.002), suggesting local virus replication in the breast milk compartment. Moreover, clonally amplified virus env genes in milk produced functional virus Envs that were all CCR5 tropic. Milk and plasma virus Envs had similar predicted phenotypes and neutralization sensitivities to broadly neutralizing antibodies in both transmitting and nontransmitting mothers. Finally, phylogenetic comparison of longitudinal milk and plasma virus env sequences revealed synchronous virus evolution and new clonal amplification of evolved virus env genes in milk. The limited compartmentalization and the clonal amplification of evolving, functional viruses in milk indicate continual seeding of the mammary gland by blood virus variants, followed by transient local replication of these variants in the breast milk compartment.
dc.language eng
dc.relation.ispartof J Virol
dc.relation.isversionof 10.1128/JVI.02316-10
dc.subject Cluster Analysis
dc.subject Evolution, Molecular
dc.subject Female
dc.subject Genetic Variation
dc.subject HIV Infections
dc.subject HIV-1
dc.subject Humans
dc.subject Infant
dc.subject Infant, Newborn
dc.subject Malawi
dc.subject Milk, Human
dc.subject Molecular Sequence Data
dc.subject Phylogeny
dc.subject Plasma
dc.subject Pregnancy
dc.subject RNA, Viral
dc.subject Receptors, CCR5
dc.subject Receptors, HIV
dc.subject Sequence Analysis, DNA
dc.subject Sequence Homology
dc.subject Viral Tropism
dc.subject env Gene Products, Human Immunodeficiency Virus
dc.title Origin and evolution of HIV-1 in breast milk determined by single-genome amplification and sequencing.
dc.type Journal article
pubs.author-url https://www.ncbi.nlm.nih.gov/pubmed/21191008
pubs.begin-page 2751
pubs.end-page 2763
pubs.issue 6
pubs.organisational-group Basic Science Departments
pubs.organisational-group Clinical Science Departments
pubs.organisational-group Duke
pubs.organisational-group Duke Human Vaccine Institute
pubs.organisational-group Immunology
pubs.organisational-group Institutes and Centers
pubs.organisational-group Medicine
pubs.organisational-group Medicine, Duke Human Vaccine Institute
pubs.organisational-group Molecular Genetics and Microbiology
pubs.organisational-group Pediatrics
pubs.organisational-group Pediatrics, Infectious Diseases
pubs.organisational-group School of Medicine
pubs.organisational-group Surgery
pubs.organisational-group Surgery, Surgical Sciences
pubs.publication-status Published
pubs.volume 85
dc.identifier.eissn 1098-5514


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