Logo image
Personalized viral genomic investigation of herpes simplex virus 1 perinatal viremic transmission with dual fatality
Journal article   Open access   Peer reviewed

Personalized viral genomic investigation of herpes simplex virus 1 perinatal viremic transmission with dual fatality

Mackenzie M Shipley, Daniel W Renner, Utsav Pandey, Bradley Ford, David C Bloom, Charles Grose and Moriah L Szpara
Cold Spring Harbor molecular case studies, Vol.5(6), p.a004382
12/2019
DOI: 10.1101/mcs.a004382
PMCID: PMC6913147
PMID: 31582464
url
https://doi.org/10.1101/mcs.a004382View
Published (Version of record) Open Access

Abstract

Here we present a personalized viral genomics approach to investigating a rare case of perinatal herpes simplex virus 1 (HSV-1) transmission that ended in death of both mother and neonate. We sought to determine whether the virus involved in this rare case had any unusual features that may have contributed to the dire patient outcome. A pregnant woman with negative HerpeSelect antibody test underwent cesarean section at 30 wk gestation and died the same day. The premature newborn died 5 d later. Both individuals were found postmortem to have positive blood HSV-1 PCR tests. Using oligonucleotide enrichment and deep sequencing, we determined that viral transmission from mother to infant was nearly perfect at the consensus genome level. At the virus population level, 77% of minor variants (MVs) in the mother's blood also appeared on the neonate's skin, of which more than half were disseminated into the neonate's blood. We also detected nonmaternal MVs that arose de novo in the neonate's viral populations. Of note, one de novo MV in the neonate's skin virus induced a nonsynonymous mutation in the UL6 protein, which is a component of the portal that allows DNA entry into new progeny capsids. This case suggests that perinatal viremic HSV-1 transmission includes the majority of genetic diversity from the maternal virus population and that new, nonsynonymous mutations can occur after relatively few rounds of replication. This report expands our understanding of viral transmission in humans and may lead to improved diagnostic strategies for neonatal HSV-1 acquisition.
herpes simplex encephalitis severe viral infections preeclampsia

Details

Metrics

Logo image