Strain Variation and Disease Severity in Congenital Cytomegalovirus Infection

Abstract

Synopsis The wide spectrum of congenital CMV disease and known differences in the biology and in vitro growth of CMV strains continue to drive studies in search for specific viral genetic determinants that may predict severity of congenital CMV disease. Several CMV genes have been studied in detail in congenitally-infected children, but the complexity of the viral genome and differences in the definition of symptomatic disease vs. asymptomatic CMV infection continue to raise questions related to what constitutes a pathogenic CMV strain. In addition, the prevalence and role of multiple CMV strains as opposed to infection with a single strain in disease severity is debated. Although the new era of highly-sensitive next generation sequencing assays may provide detailed information on multiple genetic loci, strict criteria for differentiating between strains will be required. Identifying a viral marker (or combination of markers) for prediction of disease outcome could have a major impact on pre-natal diagnosis and vaccine development. Large, well-controlled studies with long-term follow-up and use of standardized high stringency molecular techniques will be required to move the field forward. Genetic variation of host genes may play an adjunctive role in the outcome of congenital CMV disease.

Impacts of Genome-Wide Analyses on Our Understanding of Human Herpesvirus Diversity and Evolution

“…These forward genetic approaches complement prior decades of reverse genetic approaches, which established the function of herpesvirus genes and began to dissect the impacts of individual genetic variants ( 115 , 116 ). However, the occurrence of gene deletions and genetic variations in living humans can be quite distinct from those seen in laboratory-constructed mutants ( 33 , 75 , 78 ), and there is significant interest in determining if and how these viral genetic variants may impact human clinical outcomes ( 79 , 117 , 118 ). This motivates the future extension of GWAS analyses to naturally circulating viral variants and clinical isolates.…”

Maternal and fetal cytomegalovirus infection: diagnosis, management, and prevention

“…Whether these cytokine and chemokine changes at the maternal–fetal interface facilitate transplacental transmission of virus or result from fetal infection is unclear. Viral genotypes have been investigated in relation to transmissibility, but it appears that all strains are transmissible 53 .…”

Who Is the Patient at Risk of CMV Recurrence: A Review of the Current Scientific Evidence with a Focus on Hematopoietic Cell Transplantation

“…Current understanding of CMV infection underlines that co-infection with different strains occurs quite frequently, but because of stochasticity of the reactivation event, a single strain may reactivate to give rise to recurrent infection and recrudescent disease [ 13 , 14 ]. The problem in clinical studies is that the strain from a latent infection is rarely typed; however CMV strain differences might have significant potential to influence the risk of reactivation/recurrence.…”