Occurrence of Human Cytomegalovirus Glycoprotein B Genotypes in Immunocompetent and Immunosuppressed Taiwanese Patients

Wu, Keh-Gong; Hung, Miao-Chiu; Chang, Ya-Ting; Chen, Chun‐Jen; Yang, Sing Yu; Liu, Cheng-Yi; Ho, Donald Ming‐Tak; Chan, Yu‐Jiun

doi:10.1159/000322382

Cited by 7 publications

(7 citation statements)

References 46 publications

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“…Considering single gB genotypes, 12.8, 23.4, and 4.2% of patients displayed a gB1, gB2, and gB3 genotype, respectively, whereas gB4 was never found as a single infecting virus. In contrast to the data from other studies [11,12] in which gB1 was more frequent, particularly in immunosuppressed subjects, we found a higher rate of gB2; however, the limitations due to the small number of individuals in each group must be considered. Interestingly, gB4 was the least represented genotype in several studies, including ours, in which it only occurred in mixed infections.…”

confidence: 99%

Cytomegalovirus Glycoprotein B Genotype Distribution in Italian Transplant Patients

Sagnelli

Cella²,

Rittá

et al. 2017

Intervirology

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Background: The cytomegalovirus (CMV) UL55 gene encodes for a glycoprotein implicated in virus pathogenesis. Based on UL55 polymorphism, CMV has been divided into 4 genotypes. Previous studies investigated the possible role of genotypes in the clinical outcome of infection in different categories of patients; however, few data are available, particularly in the transplant setting and Italian case records. Methods: Phylogenetic analysis through a maximum likelihood tree was used to evaluate the prevalence and distribution of CMV genotypes in whole blood specimens from 47 transplant patients and investigate the relation with demographic and clinical features. Results: Overall, 40.4% of patients were classified as single genotype (12.8% gB1, 23.4% gB2, 4.2% gB3); mixed genotypes were detected in 59.6%. Genotype 4 was detected only in mixed cases. In comparison to single genotypes, mixed genotypes were more frequently associated with a higher duration of DNA viremia and higher peak viral load. Conclusions: Mixed infections seem to be prevalent in Italian transplant patients; it is likely that mixed infections are more difficult to control by immunological response in comparison to single genotype infections. In this context, the genetic profile of infecting viruses and relation to clinical outcome should be investigated, also taking into account the CMV-specific cellular immune response.

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confidence: 99%

Cytomegalovirus Glycoprotein B Genotype Distribution in Italian Transplant Patients

Sagnelli

Cella²,

Rittá

et al. 2017

Intervirology

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“…GB1 and gB2 were the most frequent genotypes in this study, and they occurred in similar proportions (39% and 35%, respectively). These results are in line with other studies, including one from our group performed in a Brazilian pediatric renal and hematopoietic stem cell transplantation cohort [7,34-37], but not with a report from Chinese HSCT patients, where gB1 and gB3 were the prevalent genotypes [38,39]. Furthermore, in our population, the proportion of mixed genotypes was rare (6%), that is comparable to recent reports which showed ranges from 5% to 25% [6,38,40].…”

Section: Discussionsupporting

confidence: 91%

Cytomegalovirus (CMV) genotype in allogeneic hematopoietic stem cell transplantation

et al. 2013

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BackgroundBased on sequence variation in the UL55 gene that encodes glycoprotein B (gB), human cytomegalovirus (CMV) can be classified into four gB genotypes. Previous studies have suggested an association between CMV gB genotype and clinical outcome in patients who underwent an allogeneic hematopoietic stem cell transplant (HSCT). The goals of this study were identify patients with active infection caused by CMV in recipients of HSCT; determine the prevalence of CMV genotypes in the study group; correlate genotype with CMV disease, acute GVHD and overall survival.MethodsThe diagnosis of active CMV infection after allogeneic HSCT was detected by antigenemia (AGM) and/or nested-PCR (N-PCR). Positive samples from patients with active CMV infection were submitted to genotyping using N-PCR to amplify a region of UL55, followed by restriction analysis based on HinfI and RsaI digestion. Real-time PCR (qPCR) was used to determine the viral load during active CMV infection and antiviral treatment.ResultsSixty-three allogeneic HSCT recipients were prospectively evaluated; 49/63 (78%) patients were infected with CMV genotypes – gB1 19/49 (39%), gB2 17/49 (35%), gB3 3/49 (6%), gB4 7/49 (14%) – and 3 (6%) had mixed CMV genotypes (gB1 + gB3, gB1 + gB4 and gB2 + gB4). Characterized by gastrointestinal disease, CMV disease occurred in 3/49 (6.1%) patients, who had CMV gB3 genotype. These gB3 genotype patients presented an increasing AGM number, mean 125 (± 250) (P = 0.70), and qPCR copies/ml, mean 37938 (SD ± 50542) (P = 0.03), during antiviral treatment, when compared with other CMV genotypes. According to CMV genotypes, stratified overall survival was 55% for gB1, 43% for gB2; 0% for gB3 and 57% for gB4 (P = 0.03).ConclusionsOne of the restrictions of the presented study was the low number of CMV gB sub-cohorts). However, we demonstrated that the frequency of active CMV infection in this HSCT population was high, and the most prevalent genotype in these patients with active CMV infection was gB1 and gB2 genotype (74%). In Brazil, HSCT recipients seem to carry mainly gB1 and gB2 CMV genotype.

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“…While we cannot completely rule out these explanations, if nucleotide diversity was predominantly determined by current viral population sizes, we would expect a positive relationship between strain nucleotide diversity and prevalence rather than the negative relationship we observed. While selective sweeps that reduce genetic diversity might obscure the increase of nucleotide diversity through time, the relationship that we observed between diversity and prevalence was robust and was also observed when using strains defined using a section of UL54, which should experience less selective pressure than the UL55-enocded glycoprotein B. Encouragingly, a similar pattern between strain age and prevalence has been observed for HCMV, where genotype gB4 is consistently the least prevalent genotype [ 32 – 36 ], despite being estimated as the oldest of the 4 glycoprotein B genotypes ( S3 Fig , S1 Text ). Although we emphasise the preliminary nature of this conclusion, if DrBHV-vectored vaccines behave similarly to wild-type DrBHV strains, our results suggest they would rise in prevalence, spread predictably within the bounds of bat population structure, and eventually become minor variants.…”

Section: Discussionsupporting

confidence: 75%

Longitudinal deep sequencing informs vector selection and future deployment strategies for transmissible vaccines

et al. 2022

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Vaccination is a powerful tool in combating infectious diseases of humans and companion animals. In most wildlife, including reservoirs of emerging human diseases, achieving sufficient vaccine coverage to mitigate disease burdens remains logistically unattainable. Virally vectored “transmissible” vaccines that deliberately spread among hosts are a potentially transformative, but still theoretical, solution to the challenge of immunising inaccessible wildlife. Progress towards real-world application is frustrated by the absence of frameworks to guide vector selection and vaccine deployment prior to major in vitro and in vivo investments in vaccine engineering and testing. Here, we performed deep sequencing on field-collected samples of Desmodus rotundus betaherpesvirus (DrBHV), a candidate vector for a transmissible vaccine targeting vampire bat–transmitted rabies. We discovered 11 strains of DrBHV that varied in prevalence and geographic distribution across Peru. The phylogeographic structure of DrBHV strains was predictable from both host genetics and landscape topology, informing long-term DrBHV-vectored vaccine deployment strategies and identifying geographic areas for field trials where vaccine spread would be naturally contained. Multistrain infections were observed in 79% of infected bats. Resampling of marked individuals over 4 years showed within-host persistence kinetics characteristic of latency and reactivation, properties that might boost individual immunity and lead to sporadic vaccine transmission over the lifetime of the host. Further, strain acquisitions by already infected individuals implied that preexisting immunity and strain competition are unlikely to inhibit vaccine spread. Our results support the development of a transmissible vaccine targeting a major source of human and animal rabies in Latin America and show how genomics can enlighten vector selection and deployment strategies for transmissible vaccines.

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Occurrence of Human Cytomegalovirus Glycoprotein B Genotypes in Immunocompetent and Immunosuppressed Taiwanese Patients

Cited by 7 publications

References 46 publications

Cytomegalovirus Glycoprotein B Genotype Distribution in Italian Transplant Patients

Cytomegalovirus Glycoprotein B Genotype Distribution in Italian Transplant Patients

Cytomegalovirus (CMV) genotype in allogeneic hematopoietic stem cell transplantation

Longitudinal deep sequencing informs vector selection and future deployment strategies for transmissible vaccines

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