Genetic analyses of HIV-1 env sequences demonstrate limited compartmentalization in breast milk and suggest viral replication within the breast that increases with mastitis

Soren Gantt, Jacquelyn Carlsson, Laura Heath, Marta E. Bull, Avinash K. Shetty, Junior Mutsvangwa, Georgina Musingwini, Godfrey Woelk, Lynn S. Zijenah, David A. Katzenstein, James I. Mullins, Lisa M. Frenkel

Research output: Contribution to journalArticle

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Abstract

The concentration of human immunodeficiency virus type 1 (HIV-1) is generally lower in breast milk than in blood. Mastitis, or inflammation of the breast, is associated with increased levels of milk HIV-1 and risk of mother-to-child transmission through breastfeeding. We hypothesized that mastitis facilitates the passage of HIV-1 from blood into milk or stimulates virus production within the breast. HIV-1 env sequences were generated from single amplicons obtained from breast milk and blood samples in a cross-sectional study. Viral compartmentalization was evaluated using several statistical methods, including the Slatkin and Maddison (SM) test. Mastitis was defined as an elevated milk sodium (Na+) concentration. The association between milk Na+ and the pairwise genetic distance between milk and blood viral sequences was modeled using linear regression. HIV-1 was compartmentalized within milk by SM testing in 6/17 (35%) specimens obtained from 9 women, but all phylogenetic clades included viral sequences from milk and blood samples. Monotypic sequences were more prevalent in milk samples than in blood samples (22% versus 13%; P = 0.012), which accounted for half of the compartmentalization observed. Mastitis was not associated with compartmentalization by SM testing (P = 0.621), but Na+ was correlated with greater genetic distance between milk and blood HIV-1 populations (P = 0.041). In conclusion, local production of HIV-1 within the breast is suggested by compartmentalization of virus and a higher prevalence of monotypic viruses in milk specimens. However, phylogenetic trees demonstrate extensive mixing of viruses between milk and blood specimens. HIV-1 replication in breast milk appears to increase with inflammation, contributing to higher milk viral loads during mastitis.

Original languageEnglish
Pages (from-to)10812-10819
Number of pages8
JournalJournal of Virology
Volume84
Issue number20
DOIs
Publication statusPublished - 01-10-2010
Externally publishedYes

Fingerprint

Mastitis
Human Milk
breast milk
virus replication
Human immunodeficiency virus 1
mastitis
breasts
HIV-1
Milk
Breast
milk
blood
Viruses
viruses
genetic distance
inflammation
Inflammation
sampling
phylogeny
breast feeding

All Science Journal Classification (ASJC) codes

  • Immunology
  • Virology

Cite this

Gantt, Soren ; Carlsson, Jacquelyn ; Heath, Laura ; Bull, Marta E. ; Shetty, Avinash K. ; Mutsvangwa, Junior ; Musingwini, Georgina ; Woelk, Godfrey ; Zijenah, Lynn S. ; Katzenstein, David A. ; Mullins, James I. ; Frenkel, Lisa M. / Genetic analyses of HIV-1 env sequences demonstrate limited compartmentalization in breast milk and suggest viral replication within the breast that increases with mastitis. In: Journal of Virology. 2010 ; Vol. 84, No. 20. pp. 10812-10819.
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title = "Genetic analyses of HIV-1 env sequences demonstrate limited compartmentalization in breast milk and suggest viral replication within the breast that increases with mastitis",
abstract = "The concentration of human immunodeficiency virus type 1 (HIV-1) is generally lower in breast milk than in blood. Mastitis, or inflammation of the breast, is associated with increased levels of milk HIV-1 and risk of mother-to-child transmission through breastfeeding. We hypothesized that mastitis facilitates the passage of HIV-1 from blood into milk or stimulates virus production within the breast. HIV-1 env sequences were generated from single amplicons obtained from breast milk and blood samples in a cross-sectional study. Viral compartmentalization was evaluated using several statistical methods, including the Slatkin and Maddison (SM) test. Mastitis was defined as an elevated milk sodium (Na+) concentration. The association between milk Na+ and the pairwise genetic distance between milk and blood viral sequences was modeled using linear regression. HIV-1 was compartmentalized within milk by SM testing in 6/17 (35{\%}) specimens obtained from 9 women, but all phylogenetic clades included viral sequences from milk and blood samples. Monotypic sequences were more prevalent in milk samples than in blood samples (22{\%} versus 13{\%}; P = 0.012), which accounted for half of the compartmentalization observed. Mastitis was not associated with compartmentalization by SM testing (P = 0.621), but Na+ was correlated with greater genetic distance between milk and blood HIV-1 populations (P = 0.041). In conclusion, local production of HIV-1 within the breast is suggested by compartmentalization of virus and a higher prevalence of monotypic viruses in milk specimens. However, phylogenetic trees demonstrate extensive mixing of viruses between milk and blood specimens. HIV-1 replication in breast milk appears to increase with inflammation, contributing to higher milk viral loads during mastitis.",
author = "Soren Gantt and Jacquelyn Carlsson and Laura Heath and Bull, {Marta E.} and Shetty, {Avinash K.} and Junior Mutsvangwa and Georgina Musingwini and Godfrey Woelk and Zijenah, {Lynn S.} and Katzenstein, {David A.} and Mullins, {James I.} and Frenkel, {Lisa M.}",
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Gantt, S, Carlsson, J, Heath, L, Bull, ME, Shetty, AK, Mutsvangwa, J, Musingwini, G, Woelk, G, Zijenah, LS, Katzenstein, DA, Mullins, JI & Frenkel, LM 2010, 'Genetic analyses of HIV-1 env sequences demonstrate limited compartmentalization in breast milk and suggest viral replication within the breast that increases with mastitis', Journal of Virology, vol. 84, no. 20, pp. 10812-10819. https://doi.org/10.1128/JVI.00543-10

Genetic analyses of HIV-1 env sequences demonstrate limited compartmentalization in breast milk and suggest viral replication within the breast that increases with mastitis. / Gantt, Soren; Carlsson, Jacquelyn; Heath, Laura; Bull, Marta E.; Shetty, Avinash K.; Mutsvangwa, Junior; Musingwini, Georgina; Woelk, Godfrey; Zijenah, Lynn S.; Katzenstein, David A.; Mullins, James I.; Frenkel, Lisa M.

In: Journal of Virology, Vol. 84, No. 20, 01.10.2010, p. 10812-10819.

Research output: Contribution to journalArticle

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T1 - Genetic analyses of HIV-1 env sequences demonstrate limited compartmentalization in breast milk and suggest viral replication within the breast that increases with mastitis

AU - Gantt, Soren

AU - Carlsson, Jacquelyn

AU - Heath, Laura

AU - Bull, Marta E.

AU - Shetty, Avinash K.

AU - Mutsvangwa, Junior

AU - Musingwini, Georgina

AU - Woelk, Godfrey

AU - Zijenah, Lynn S.

AU - Katzenstein, David A.

AU - Mullins, James I.

AU - Frenkel, Lisa M.

PY - 2010/10/1

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N2 - The concentration of human immunodeficiency virus type 1 (HIV-1) is generally lower in breast milk than in blood. Mastitis, or inflammation of the breast, is associated with increased levels of milk HIV-1 and risk of mother-to-child transmission through breastfeeding. We hypothesized that mastitis facilitates the passage of HIV-1 from blood into milk or stimulates virus production within the breast. HIV-1 env sequences were generated from single amplicons obtained from breast milk and blood samples in a cross-sectional study. Viral compartmentalization was evaluated using several statistical methods, including the Slatkin and Maddison (SM) test. Mastitis was defined as an elevated milk sodium (Na+) concentration. The association between milk Na+ and the pairwise genetic distance between milk and blood viral sequences was modeled using linear regression. HIV-1 was compartmentalized within milk by SM testing in 6/17 (35%) specimens obtained from 9 women, but all phylogenetic clades included viral sequences from milk and blood samples. Monotypic sequences were more prevalent in milk samples than in blood samples (22% versus 13%; P = 0.012), which accounted for half of the compartmentalization observed. Mastitis was not associated with compartmentalization by SM testing (P = 0.621), but Na+ was correlated with greater genetic distance between milk and blood HIV-1 populations (P = 0.041). In conclusion, local production of HIV-1 within the breast is suggested by compartmentalization of virus and a higher prevalence of monotypic viruses in milk specimens. However, phylogenetic trees demonstrate extensive mixing of viruses between milk and blood specimens. HIV-1 replication in breast milk appears to increase with inflammation, contributing to higher milk viral loads during mastitis.

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