Cytomegalovirus gN genotypes distribution among congenitally infected newborns and their relationship with symptoms at birth and sequelae.
BACKGROUND
Cytomegalovirus (CMV) is the leading cause of congenital infection, with morbidity and mortality at birth and sequelae. Both host and viral factors may affect the outcome of infection. CMV strain virulence may depend on genetic variability in "key genes," such as UL73, which encodes the envelope glycoprotein gN. This study aimed to ascertain the role of gN variants as markers of pathogenicity and prognosis in newborns congenitally infected with CMV.


METHODS
Seventy-four congenitally infected newborns were monitored for symptoms of CMV disease at birth and during long-term follow-up. The distribution of gN variants was analyzed in relation to virological parameters, clinical signs, laboratory and instrumental abnormalities at birth, and sequelae. Multivariate cluster analysis was used to test for differences in the distribution of variables. An independent validation cohort of the same size and modality of recruitment as the original population was examined by logistic regression to validate results.


RESULTS
Univariate and cluster analyses suggest that newborns congenitally infected with CMV fall into 2 subpopulations on the basis of definite parameters of CMV disease. The first population with no symptoms at birth, negative instrumental findings, and a favorable long-term outcome was significantly associated with gN-1 and gN-3a genotypes. The second group with symptoms at birth, abnormal imaging results, and sequelae was associated with gN-4 genotypes (P<.05). The validation cohort further supports the results, indicating that genotypes gN-1 or gN-3a reduce the risk of sequelae 5 fold (95% confidence interval, 1.3-15.6 fold), whereas variants belonging to group gN-4 increase the risk of sequelae 8 fold (95% confidence interval, 2.6-25.8 fold).


CONCLUSIONS
Results suggest that gN genotypes might be markers for virulence of CMV wild-type strains and a discriminating factor for selection of CMV-infected newborns who are at risk of developing sequelae.
Pignatelli
Sara
S
Department of Haematology, Oncology and Laboratory Medicine, Clinical Unit of Microbiology, St. Orsola Malpighi General Hospital, University of Bologna, Bologna, Italy. sara.pignatelli@unibo.it
Lazzarotto
Tiziana
T
Gatto
Maria R
MR
Dal Monte
Paola
P
Landini
Maria P
MP
Faldella
Giacomo
G
Lanari
Marcello
M
D000704:Analysis of Variance; D016000:Cluster Analysis; D003587:Cytomegalovirus / Q000235:genetics* / Q000472:pathogenicity; D003586:Cytomegalovirus Infections / Q000150:complications / Q000151:congenital* / Q000821:virology; D005260:Female; D005500:Follow-Up Studies; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007231:Infant, Newborn; D016015:Logistic Models; D008297:Male; D015999:Multivariate Analysis; D011379:Prognosis; D015203:Reproducibility of Results; D012307:Risk Factors