Vertical transmission of X4-tropic and dual-tropic HIV-1 in five Ugandan mother-infant pairs.
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.
Huang
Wei
W
Monogram Biosciences, South San Francisco, California, USA. whuang@monogrambio.com
Eshleman
Susan H
SH
Toma
Jonathan
J
Stawiski
Eric
E
Whitcomb
Jeannette M
JM
Jackson
J Brooks
JB
Guay
Laura
L
Musoke
Philippa
P
Parkin
Neil
N
Petropoulos
Christos J
CJ
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
C527276:CXCR4 protein, human; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments; D019718:Receptors, CXCR4