Document Detail


Vertical transmission of X4-tropic and dual-tropic HIV-1 in five Ugandan mother-infant pairs.
MedLine Citation:
PMID:  19593079     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: We previously reported the existence of CXCR4-using HIV-1 in 6-14 week-old Ugandan infants. Whether these viruses were transmitted from the mother perinatally or evolved after transmission is not known. In the current study, we investigated the origin of the CXCR4-using viruses in these infants by comparing HIV-1 envelope clones from the infants to those from their mothers at or near the time of delivery.
METHODS: Envelope clones were isolated from five Ugandan infant plasma samples that harbored CXCR4-using viruses, collected at the time of HIV diagnosis (four at birth, one at week 6), and from their mothers at delivery. Coreceptor usage and phylogenetic relatedness of HIV-1 populations in mother-infant pairs were analyzed in detail using the Trofile assay and sequence analysis of envelope clones, respectively.
RESULTS: X4-tropic clones were identified in two mother-infant pairs and dual-tropic clones were found in three pairs, either alone or in combination with R5-tropic viruses. Dual-tropic clones varied in their ability to infect CXCR4-expressing cells. In each mother-infant pair, X4-tropic or dual-tropic clones shared similar phenotypic profiles and V3 sequence patterns; gp160 sequences of X4-tropic and dual-tropic clones from infants were phylogenetically indistinguishable from those of their mothers. The virus populations were phylogenetically homogenous in three infants and segregated according to coreceptor tropism in the remaining two infants.
CONCLUSIONS: This study demonstrates that X4-tropic and dual-tropic HIV-1 can be transmitted from mother to infant, before, during or shortly after delivery, and establishes vertical transmission as an important source of CXCR4-using viruses in infants.
Authors:
Wei Huang; Susan H Eshleman; Jonathan Toma; Eric Stawiski; Jeannette M Whitcomb; J Brooks Jackson; Laura Guay; Philippa Musoke; Neil Parkin; Christos J Petropoulos
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  AIDS (London, England)     Volume:  23     ISSN:  1473-5571     ISO Abbreviation:  AIDS     Publication Date:  2009 Sep 
Date Detail:
Created Date:  2009-08-27     Completed Date:  2010-01-28     Revised Date:  2012-07-25    
Medline Journal Info:
Nlm Unique ID:  8710219     Medline TA:  AIDS     Country:  England    
Other Details:
Languages:  eng     Pagination:  1903-8     Citation Subset:  IM; X    
Copyright Information:
2009 Wolters Kluwer Health | Lippincott Williams & Wilkins
Affiliation:
Monogram Biosciences, South San Francisco, California, USA. whuang@monogrambio.com
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Female
HIV Envelope Protein gp120 / genetics
HIV Infections / transmission*,  virology
HIV-1 / genetics*,  metabolism
Humans
Infant
Infant, Newborn
Infectious Disease Transmission, Vertical*
Molecular Sequence Data
Peptide Fragments / genetics
Phylogeny
Pregnancy
Pregnancy Complications, Infectious / virology*
Prenatal Exposure Delayed Effects
Receptors, CXCR4 / metabolism
Grant Support
ID/Acronym/Agency:
N01-AI-35173/AI/NIAID NIH HHS; N01-AI-45200/AI/NIAID NIH HHS; N0I-AI-35173-417/AI/NIAID NIH HHS; R43 AI048990/AI/NIAID NIH HHS; R44-AI-048990/AI/NIAID NIH HHS; U01 AI068613-04/AI/NIAID NIH HHS; U01 AI068632-03/AI/NIAID NIH HHS; U01-AI-068613/AI/NIAID NIH HHS; U01-AI-068632/AI/NIAID NIH HHS; U01-AI-46745/AI/NIAID NIH HHS; U01-AI-48054/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/CXCR4 protein, human; 0/HIV Envelope Protein gp120; 0/HIV envelope protein gp120 (305-321); 0/Peptide Fragments; 0/Receptors, CXCR4
Comments/Corrections

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