Genotypic and phenotypic diversity of herpes simplex virus 2 within the infected neonatal population

Lisa N. Akhtar, Christopher D. Bowen, Daniel W. Renner, Utsav Pandey, Ashley N. Della Fera, David W. Kimberlin, Mark N. Prichard, Richard J. Whitley, Matthew D. Weitzman, Moriah L. Szpara

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

ABSTRACT More than 14,000 neonates are infected with herpes simplex virus (HSV) annually. Approximately half display manifestations limited to the skin, eyes, or mouth (SEM disease). The rest develop invasive infections that spread to the central nervous system (CNS disease or encephalitis) or throughout the infected neonate (disseminated disease). Invasive HSV disease is associated with significant morbidity and mortality, but the viral and host factors that predispose neonates to these forms are unknown. To define viral diversity within the infected neonatal population, we evaluated 10 HSV-2 isolates from newborns with a range of clinical presentations. To assess viral fitness independently of host immune factors, we measured viral growth characteristics in cultured cells and found diverse in vitro phenotypes. Isolates from neonates with CNS disease were associated with larger plaque size and enhanced spread, with the isolates from cerebrospinal fluid (CSF) exhibiting the most robust growth. We sequenced complete viral genomes of all 10 neonatal viruses, providing new insights into HSV-2 genomic diversity in this clinical setting. We found extensive interhost and intrahost genomic diversity throughout the viral genome, including amino acid differences in more than 90% of the viral proteome. The genes encoding glycoprotein G (gG; US4), glycoprotein I (gI; US7), and glycoprotein K (gK; UL53) and viral proteins UL8, UL20, UL24, and US2 contained variants that were found in association with CNS isolates. Many of these viral proteins are known to contribute to cell spread and neurovirulence in mouse models of CNS disease. This report represents the first application of comparative pathogen genomics to neonatal HSV disease.

Original languageEnglish (US)
Article numbere00590-18
JournalmSphere
Volume4
Issue number1
DOIs
StatePublished - Jan 1 2019

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Human Herpesvirus 2
Central Nervous System Diseases
Simplexvirus
Glycoproteins
Viral Genome
Viral Proteins
Virus Diseases
Population
Mouth Diseases
Immunologic Factors
Encephalitis
Proteome
Growth
Genomics
Cerebrospinal Fluid
Cultured Cells
Viruses
Morbidity
Phenotype
Amino Acids

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Molecular Biology

Cite this

Akhtar, L. N., Bowen, C. D., Renner, D. W., Pandey, U., Della Fera, A. N., Kimberlin, D. W., ... Szpara, M. L. (2019). Genotypic and phenotypic diversity of herpes simplex virus 2 within the infected neonatal population. mSphere, 4(1), [e00590-18]. https://doi.org/10.1128/mSphere.00590-18
Akhtar, Lisa N. ; Bowen, Christopher D. ; Renner, Daniel W. ; Pandey, Utsav ; Della Fera, Ashley N. ; Kimberlin, David W. ; Prichard, Mark N. ; Whitley, Richard J. ; Weitzman, Matthew D. ; Szpara, Moriah L. / Genotypic and phenotypic diversity of herpes simplex virus 2 within the infected neonatal population. In: mSphere. 2019 ; Vol. 4, No. 1.
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Akhtar, LN, Bowen, CD, Renner, DW, Pandey, U, Della Fera, AN, Kimberlin, DW, Prichard, MN, Whitley, RJ, Weitzman, MD & Szpara, ML 2019, 'Genotypic and phenotypic diversity of herpes simplex virus 2 within the infected neonatal population', mSphere, vol. 4, no. 1, e00590-18. https://doi.org/10.1128/mSphere.00590-18

Genotypic and phenotypic diversity of herpes simplex virus 2 within the infected neonatal population. / Akhtar, Lisa N.; Bowen, Christopher D.; Renner, Daniel W.; Pandey, Utsav; Della Fera, Ashley N.; Kimberlin, David W.; Prichard, Mark N.; Whitley, Richard J.; Weitzman, Matthew D.; Szpara, Moriah L.

In: mSphere, Vol. 4, No. 1, e00590-18, 01.01.2019.

Research output: Contribution to journalArticle

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AU - Della Fera, Ashley N.

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Akhtar LN, Bowen CD, Renner DW, Pandey U, Della Fera AN, Kimberlin DW et al. Genotypic and phenotypic diversity of herpes simplex virus 2 within the infected neonatal population. mSphere. 2019 Jan 1;4(1). e00590-18. https://doi.org/10.1128/mSphere.00590-18