Table 3 Viral/host factors of potential importance in cCMV pathogenesis/sequelae risk.

From: Beyond hearing loss: exploring neurological and neurodevelopmental sequelae in asymptomatic congenital cytomegalovirus infection

Candidate biomarkers potentially predicting CNS sequelae in cCMV

Viral Factors

• Viral Strain Variation.

 ◦ Enhanced pathogenicity of specific viral genotypes.

 ◦ Viral envelope glycoprotein genotypes associated with increased risk of sequelae.

 ◦ Strain variation/lack of strain-specific immunity promoting immune escape.

 ◦ Re-infection in seropositives.

 ◦ Would sequencing infant viral strains/assigning strain genotypes provide prediction of risk of sequelae?

• Infection Mediating Immunopathogenesis and Host Immune/Inflammatory Response.

 ◦ Modification of host cytokine and chemokine responses.

 ◦ Viral immediate early (IE) gene, anti-apoptotic genes, viral cytokine/chemokine proteins, G-protein coupled receptors, TNFα and interleukin homologs.

Host Factors

• Injury to Host Chromosome

 ◦ 1q23.3/DFNA7 locus.

 ◦ 1q42/USH2A.

• Interaction of CMV with Host SNPs.

 ◦ Cytokine promoters.

 ◦ TLR promoters.

 ◦ Gene-gene interactions, e.g., GJB2.

• Disruption of Genes that are Key Components of Fetal Brain Transcriptome with Resulting Neuronal Migration Abnormalities.

 ◦ LIS1.

 ◦ NID1.

• Systemic Transcriptome Analyses in Children with Sequelae and Unaffected cCMV Controls.

 ◦ 16-gene “signature” associated with SNHL.

 ◦ ARHGEF9.

 ◦ MPDU1.

 ◦ CD40.

 ◦ Would measurement of host transcriptional responses provide clues to prognosis and help individual patient management/therapy decision-making?

• Host Production of Neurotoxic Cytokines and Reactive Oxygen Species.

 ◦ Could the measurement of cytokine, chemokine or virus-specific immune responses in infants help to profile risk and to guide prognosis/clinical management?

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