Genotypes of glycoprotein B gene among the Indian symptomatic neonates with congenital CMV infection

Abstract

Background Cytomegalovirus [CMV] is a causative agent of congenital infection worldwide and often leads to neurological deficits and hearing loss in newborns. Infants born with symptomatic congenital Cytomegalovirus infection [cCMV] are at significant high risk for developing adverse long-term outcomes. In this study, we look into the sequence variability of surface glycoprotein B [gB] encoding region in newborns with symptomatic CMV infection for the first time in Eastern region of India. Methods 576 suspected newborns from seropositive mothers were subjected to the study and ELISA was used to confirm CMV infection. Different genotypes and their subtypes were determined using multiplex nested-PCR. Viral load of different glycoprotein B [gB] genotypes was measured using RT-PCR. Sequencing and phylogenetic analysis was then performed using Bayesian interference. Results The overall frequency of cCMV infection was 18.4%, where 16.0% neonates were symptomatic. Among the different gB genotypes, gB1 had the highest frequency [23.5%] and gB4 showed the lowest occurrence [5.8%]. 23.5% of symptomatic neonates had mixed genotypes of gB, probably indicating matrenal reinfection with CMV strains in Indian population. Significant genotypic clades [gB1-gB2-gB3-gB5] were grouped closely based on gene sequences, but the gB4 sequence was in the outlier region of the phylogenetic tree indicating the genetic polymorphism. Conclusion This is the first study on cCMV genotyping and its phylogenetic analysis from Eastern Indian neonatal population. The study holds importance in the assessment of cCMV seroprevalence in global perspective. gB protein can be used as a potential therapeutic target against CMV infection.

Common Polymorphisms in the Glycoproteins of Human Cytomegalovirus and Associated Strain-Specific Immunity

“…Compared to a single gB genotype infection, mixed gB genotype infections are frequently reported in organ/bone marrow transplant recipients and AIDS patients [105,118,125,128,129,152]. Multiple studies have also demonstrated that mixed infections are able to be transmitted in utero [63,68,[74][75][76][77]109,122,134,137,138,141]. Although there is no established association between single genotype infections and disease outcomes, patients with mixed gB genotype infections have been reported to have faster disease progression or higher viral loads [83,97,102,144].…”

Significance of Cytomegalovirus gB Genotypes in Adult Patients Undergoing Hematopoietic Stem Cell Transplantation: Insights from a Single-Centre Investigation

“…The first five genotypes have been detected in Asia, Europe, and North America. However, their geographic distribution differs: gB1 is the most prevalent genotype in Asia and Egypt [ 6 , 14 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 ]; gB1 and gB2 are frequently detected in North America [ 39 , 40 , 41 , 42 , 43 , 44 , 45 ]; in South America, the most frequent genotypes were gB1 and gB2 [ 9 , 10 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 ] whereas gB1, gB2, and gB3 are commonly observed across Europe (with the exception of Serbia where gB4 is the most prevalent genotype) [ 55 , 56 , 57 , 58 , 59 ...…”

Distribution of CMV envelope glycoprotein B, H and N genotypes in infants with congenital cytomegalovirus symptomatic infection

“…Paradowska et al demonstrated that the gB2 genotype was prevalent in Polish newborns with symptomatic cCMV infection ( 48 , 66 ). However, Sarkar et al ( 17 ) demonstrated that gB1 was the most widespread genotype among Indian neonates with symptomatic cCMV infection. Another two cohorts also confirmed our findings that gB1 was the most common genotype in neonates and infants with symptomatic cCMV infection ( 57 , 67 ).…”

“…cCMV infection contributes more to the permanent disabilities of infants and young children than other congenital diseases ( 14 – 16 ). Neonates with symptomatic CMV infections are at even higher risk for the adverse neurodevelopmental sequelae and proved to be associated with many severe clinical manifestations ( 17 ).…”