Ganna Galitska1, Matteo Biolatti1, Marco De Andrea2, Agata Leone3, Alessandra Coscia3, Luigi Bertolotti4, Ugo Ala5, Enrico Bertino3, Valentina Dell'Oste6, Santo Landolfo7. 1. Department of Public Health and Pediatric Sciences, University of Turin, Turin, Italy. 2. Department of Public Health and Pediatric Sciences, University of Turin, Turin, Italy; Department of Translational Medicine, Novara Medical School, Novara, Italy. 3. Neonatal Unit, Department of Public Health and Pediatric Sciences, University of Turin, Turin, Italy. 4. Department of Veterinary Science, University of Turin, Grugliasco, Italy. 5. Department of Molecular Biotechnology and Health Sciences, University of Turin, Turin, Italy. 6. Department of Public Health and Pediatric Sciences, University of Turin, Turin, Italy. Electronic address: valentina.delloste@unito.it. 7. Department of Public Health and Pediatric Sciences, University of Turin, Turin, Italy. Electronic address: santo.landolfo@unito.it.
Abstract
BACKGROUND: Human cytomegalovirus (HCMV) is the leading cause of congenital infections resulting in severe morbidity and mortality among infected children. Although the virus is highly polymorphic, particularly in genes contributing to immune evasion, the mechanisms underlying its genetic variability and pathogenicity are only partially understood. OBJECTIVES: We aimed to characterize different HCMV clinical strains isolated from 21 congenitally- or postnatally-infected children for in vitro growth properties and genetic polymorphisms. STUDY DESIGN: The growth of various HCMV isolates was analyzed in different cell culture models. Genetic polymorphism was assessed by genetic and phylogenetic analysis of viral genes involved in virulence (UL144, US28, and UL18), latency (UL133-138), or drug resistance (UL54 and UL97). RESULTS: Here, we report a high degree of genetic and phenotypic diversity in distinct HCMV clinical isolates, as shown by their in vitro growth properties. In particular, HCMV isolates displayed the highest degree of genetic variability in the UL144 gene, where we were able to define four distinct genotypes within the cohort based on UL144 heterogeneity. Lastly, among all isolates we were able to identify 36 mutations in UL54 and 2 in UL97. CONCLUSIONS: Our findings indicate that surprisingly high levels of genetic HCMV variability correlate with a high degree of phenotypic polymorphism, which in turn might differentially influence the growth, fitness, and drug susceptibility of HCMV.
BACKGROUND:Human cytomegalovirus (HCMV) is the leading cause of congenital infections resulting in severe morbidity and mortality among infected children. Although the virus is highly polymorphic, particularly in genes contributing to immune evasion, the mechanisms underlying its genetic variability and pathogenicity are only partially understood. OBJECTIVES: We aimed to characterize different HCMV clinical strains isolated from 21 congenitally- or postnatally-infected children for in vitro growth properties and genetic polymorphisms. STUDY DESIGN: The growth of various HCMV isolates was analyzed in different cell culture models. Genetic polymorphism was assessed by genetic and phylogenetic analysis of viral genes involved in virulence (UL144, US28, and UL18), latency (UL133-138), or drug resistance (UL54 and UL97). RESULTS: Here, we report a high degree of genetic and phenotypic diversity in distinct HCMV clinical isolates, as shown by their in vitro growth properties. In particular, HCMV isolates displayed the highest degree of genetic variability in the UL144 gene, where we were able to define four distinct genotypes within the cohort based on UL144 heterogeneity. Lastly, among all isolates we were able to identify 36 mutations in UL54 and 2 in UL97. CONCLUSIONS: Our findings indicate that surprisingly high levels of genetic HCMV variability correlate with a high degree of phenotypic polymorphism, which in turn might differentially influence the growth, fitness, and drug susceptibility of HCMV.
Authors: Camden R Bair; Wei Zhang; Gabriel Gonzalez; Arash Kamali; Daniel Stylos; Jorge C G Blanco; Adriana E Kajon Journal: J Virol Date: 2021-07-07 Impact factor: 6.549
Authors: Sina Brenner; Berenike Braun; Clarissa Read; Tatjana Weil; Paul Walther; Thomas Schrader; Jan Münch; Jens von Einem Journal: Viruses Date: 2021-08-25 Impact factor: 5.048