[Thesis]. Manchester, UK: The University of Manchester; 2018.
HCMV is a common viral pathogen that infects most of the world's population by early
adulthood. It is typically asymptomatic in immunologically healthy individuals but
causes severe disease in immunocompromised patients and congenitally infected infants.
HCMV glycoproteins are highly polymorphic, and various types of associations have
been suggested between glycoprotein types and the pathogenicity of the virus. Several
studies on viruses other than HCMV have related the glycosylation of the viral glycoproteins
to virulence. This project aimed to determine whether there is a robust relationship
between the individual glycoprotein sequence and its glycosylation, how this influences
the growth characteristic of the virus and whether this is related to its pathogenicity.
Glycosylation patterns of 89 clinical specimens of different infection categories
and specimen types were correlated with genetic sequence alterations of the virus
glycoproteins (gB, gH, gL, gM, gN, gO), followed by determining whether mutation results
in specific changes in glycosylation. The aim was approached using a cell culture
model and a quantitative lectin-based assay (ELLA). A significantly increased glycosylation
level for the following genotypes: mixed gH, gN4a, gO4, mixed gL was detected. Whereas
a decreased pattern was found to be associated with gH1, gH2, gN3a, gO1a and gL2 genotypes
(P<0.05). Glycoproteins of strains isolated from respiratory specimens were significantly
highly glycosylated compared to the blood and urine samples, and from blood specimens
compared to the urine samples (P<0.05). Furthermore, strains from congenitally infected
infants and urine samples had a significantly higher growth rate than others tested.
No direct association between the virus growth and its virulence was found. These
findings demonstrate that glycosylation of glycoproteins in HCMV is affected by the
glycoprotein polymorphisms and signifies a potentially important mechanism for avoidance
of antibody-mediated neutralization, which, in turn, facilitates HCMV pathogenicity.
This phenomenon requires further study and may have application for the selection
of novel targets for diagnosis, vaccine development and other preventive measures
to combat diseases caused by this virus.