University of Turin, Italy
Student: Ganna Galitska, Ph.D. fellow
Supervisor: Prof. Santo Landolfo, M.D.
Co-Supervisor: Prof. Marco de Andrea
Human cytomegalovirus (HCMV) is the leading cause of significant morbidity and mortality in neonates related to an infectious agent. Prevention and clinical interventions for HCMV disease are limited by the absence of an effective vaccine as well as resistance to antiviral drugs and therapeutic neutralizing antibodies. Recently, it has been proposed that HCMV disease and pathogenesis may be affected by the genetic variability of the virus, which is exceptionally high both within and between hosts. Virus load, replication rate and clinical sequels of the congenitally infected infants may thus result from HCMV genetic polymorphism. Although it is known that HCMV can extensively hijack cellular genes that may contribute to its immune evasion capability and that the virus is polymorphic among hosts, the source of genomic variability and the biological relevance remain unresolved.
In this study, we aim to analyze inter-host and intra-host genomic variability of the HCMV clinical isolates from congenitally infected infants by sequencing polymorphic DNA regions with subsequent phylogenetic tree construction to identify the correlation of viral phenotypes with phylogeny. In addition, in vitro characterization of the HCMV phenotypes is performed by a variety of functional assays that help to clarify its replication properties and recognition by host restriction factors. Furthermore, we aim to unveil the clinical impact of the genetic polymorphism associated with the viral protein variability. Based on the correlation of in vitro results with the in vivo patient database, we plan to demonstrate the clinical significance of HCMV genetic diversity in predicting the impact of viral protein variability on congenital HCMV disease outcome and to provide novel diagnostic tools with which to tailor medical interventions.
Santo Landolfo, Professor
Department of Public Health and Pediatric Sciences
School of Medicine
University of Turin