title: Vertical transmission of X4-tropic and dual-tropic HIV-1 in five Ugandan mother-infant pairs.
abstract: 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: Monogram Biosciences, South San Francisco, California, USA. whuang@monogrambio.com
authors: Wei
authors: W
authors: Huang
authors: Susan H
authors: SH
authors: Eshleman
authors: Jonathan
authors: J
authors: Toma
authors: Eric
authors: E
authors: Stawiski
authors: Jeannette M
authors: JM
authors: Whitcomb
authors: J Brooks
authors: JB
authors: Jackson
authors: Laura
authors: L
authors: Guay
authors: Philippa
authors: P
authors: Musoke
authors: Neil
authors: N
authors: Parkin
authors: Christos J
authors: CJ
authors: Petropoulos
mesh_terms: D000595:Amino Acid Sequence; D005260:Female; D015699:HIV Envelope Protein gp120 / Q000235:genetics; D015658:HIV Infections / Q000635:transmission* / Q000821:virology; D015497:HIV-1 / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000235:genetics; D010802:Phylogeny; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000821:virology*; D011297:Prenatal Exposure Delayed Effects; D019718:Receptors, CXCR4 / Q000378:metabolism
chemical_list: C527276:CXCR4 protein, human; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments; D019718:Receptors, CXCR4