Cristina Venturini, UCL Department of Infection, Immunity & Inflamation

UGI Seminar
Wednesday, 15 January @ 2pm
1-19 Torrington Place, G12 (map)

Cytomegalovirus genetic diversity and evolution: insights into genotypes and their role in viral pathogenesis

Abstract: Human cytomegalovirus (HCMV) is a ubiquitous virus that infects most of the human population and presents a wide range of phenotypes. While HCMV infections are typically asymptomatic in immunocompetent individuals, the virus is the leading infectious cause of congenital disabilities and can cause severe or fatal diseases in immunocompromised individuals. The high genetic variability among HCMV strains, coupled with frequent reinfection and recombination, poses significant challenges for the development of effective vaccines.

In this talk, I will present an analysis of the genomic landscape of HCMV. Genetic differences among HCMV strains span the entire genome, with certain regions exhibiting markedly higher variability. These "hypervariable" or "multi-allelic" regions are of particular interest due to their potential role in viral adaptation and immune evasion. To precisely define the boundaries of these regions and quantify their allelic diversity, we applied a hidden Markov Model (HMM) approach to 253 publicly available HCMV genomes. This analysis revealed distinct evolutionary patterns: while much of the genome is shaped by geographically linked founder effects, some hypervariable regions display evidence of balancing selection, suggesting selective pressures that maintain allele diversity across populations, regardless of geographic origin.

These findings raise critical questions about the functional significance of HCMV genomic variation. Are specific genetic differences associated with distinct biological phenotypes or clinical outcomes? Understanding these links could illuminate how viral diversity influences disease progression and immune response, ultimately guiding the design of more targeted interventions, including vaccines and therapeutics.