Cytomegalovirus (CMV) is the leading congenital infection globally, resulting in an enormous
burden of childhood hearing loss and neurodevelopmental delay. The 20 million women living with
HIV (WLWH) worldwide are more likely to have active CMV replication than women without HIV
and are more likely to transmit CMV to the 1.3 million HIV-exposed infants born annually. Combining
genome-wide serologic and virologic analyses, this project will use existing samples to new tools to
characterize CMV reinfection and shedding during pregnancy. We will also explore the role of specific
genotypes among strains causing maternal reinfection and congenital or postnatal infant infections.
Leveraging existing longitudinal samples from 329 WLWH and their children (collected during
pregnancy, at delivery, and until 6 weeks postpartum), we will address the following specific aims:
1) Estimate the frequency of CMV reinfection during pregnancy among WLWH using novel serologic
2) Determine the association between reinfection and CMV replication of specific viral strains during
pregnancy in WLWH.
3) Identify genotypic features associated with transmission to pregnant women or their children.
Serological profiling will be done using traditional CMV strain-specific antibodies and novel
VirScan technology. VirScan allows comprehensive serological profiling using a phage display library
that we have adapted to be able to identify all antibodies to all (>10,000) sequenced CMV
strains/variants. CMV shedding will be determined by quantitative PCR on maternal & infant saliva
and maternal blood & vaginal swabs. CMV genomic analyses will be conducted on PCR positive
samples using next-generation sequencing techniques combined with machine learning. The strains
present in pregnant women will be characterized and those transmitted to infants will be sequenced.
Single nucleotide polymorphisms in genes that distinguish transmitted from non-transmitted viruses
with potential functional significance will be identified. Statistical analyses will evaluate associations
between CMV/HIV parameters and outcomes of interest including maternal reinfection and
The knowledge gained from this project may result in preventative recommendations for
maternal reinfections based on newly elucidated risk factors specific to WLWH, treatment for
reinfection during pregnancy, and prevention of congenital infection. Finally, this may help to reduce
the enormous burden of CMV infection on families affected by HIV, by informing which CMV
genotypes result in CMV transmission and should therefore be included in candidate vaccines.