Cytomegalovirus Glycoprotein B Genotype Distribution in Italian Transplant Patients

Sagnelli, Caterina; Cella, Eleonora; Rittá, Massimo; Ciccozzi, Massimo; Cavallo, Rossana; Perno, Carlo Federico; Costa, Cristina

doi:10.1159/000486593

Cited by 13 publications

(18 citation statements)

References 14 publications

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“…Thus, it is currently difficult to draw a conclusion as to whether there is a specific gB genotype that leads to a more severe disease progression. 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].…”

Section: Gbmentioning

confidence: 99%

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

Wang

Valencia

Pfeifer

et al. 2021

Viruses

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Human cytomegalovirus (HCMV), one of the most prevalent viruses across the globe, is a common cause of morbidity and mortality for immunocompromised individuals. Recent clinical observations have demonstrated that mixed strain infections are common and may lead to more severe disease progression. This clinical observation illustrates the complexity of the HCMV genome and emphasizes the importance of taking a population-level view of genotypic evolution. Here we review frequently sampled polymorphisms in the glycoproteins of HCMV, comparing the variable regions, and summarizing their corresponding geographic distributions observed to date. The related strain-specific immunity, including neutralization activity and antigen-specific cellular immunity, is also discussed. Given that these glycoproteins are common targets for vaccine design and anti-viral therapies, this observed genetic variation represents an important resource for future efforts to combat HCMV infections.

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Section: Gbmentioning

confidence: 99%

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

Wang

Valencia

Pfeifer

et al. 2021

Viruses

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“…There is growing evidence that the occurrence of mixed genotype infections serves as a marker of severe or prolonged complications from CMV infections in SOT and HSCT recipients [5,6,25,28,[44][45][46].Whether these observations can be extrapolated to the non-HSCT setting is yet to be elucidated. In agreement with a previous report in immunocompromised patients [5], our data showed that patients who were infected with mixed gB genotypes developed higher initial levels of CMV loads and had significantly more concomitant infection with other HHVs than patients infected with single gB genotypes.…”

Section: Discussionmentioning

confidence: 99%

“…Larger epidemiological studies and improved genotype-specific real-time PCR-based assays and high-throughput sequencing technology may reveal a high level of intrahost variability and offer strong evidence that CMV exists as a complex mixture of variants in immunocompromised patients and may also clarify more the epidemiological and the clinical impact of these variants. The genetic profile of infecting viruses and relation to clinical outcome should be investigated, taking into account the host’s innate and adaptive immune responses [ 4 , 8 , 45 , 50 , 51 ].…”

Section: Discussionmentioning

confidence: 99%

Cytomegalovirus Glycoprotein Polymorphisms and Increasing Viral Load in Non-Transplant Patients with Hematological Malignancies Undergoing Chemotherapy: A Prospective Observational Study

et al. 2021

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Introduction: Cytomegalovirus (CMV) predisposes to several clinical complications and is a major cause of morbidity and mortality in immunocompromised patients, including patients with hematological malignancies (HM). The present study was carried out to determine the distribution of CMV glycoprotein B, N, and O (gB, gN, and gO) genotypes and their potential effect on its viral load and on clinical outcomes in a cohort of Tunisian nonhematopoietic stem cell transplant (HSCT) patients with HM undergoing chemotherapy. Methods: CMV viral load was evaluated by realtime quantitative PCR. The gB, gN, and gO genotypes of the CMV strains were analyzed by multiplex nested PCR and sequencing. Results: This prospective study involved 60 clinical isolates obtained from 60 non-HSCT patients with HM undergoing chemotherapy. Mixed CMV gB, gN, and gO genotypes were the predominant glycoprotein genotypes in 31%, 41.4%, and 46.4% of patients, respectively. Mixed gB genotypes were associated with higher initial levels of CMV load (p = 0.001), increased rate of fever (0.025), and co-infection with other herpesviruses (HHVs) (p = 0.024) more frequently than in single gB genotype. Mixed gN genotypes were more associated with severe lymphopenia (ALC \ 500/lL) (p = 0.01) and increased risk of death (p = 0.042) than single gN genotype. Single gO2b genotype had also a more unfavorable outcome (p = 0.009) than the other single gO genotype. Mixed gO genotypes were associated with female gender (p = 0.015), acute leukemia disease (p = 0.036), initial high level of CMV viral load (at least 1000 copies/mL) (p = 0.029), skin rash (p = 0.01) more frequently than in single gO genotype. The gO1a/gN3b linkage was associated with an increased initial viral load (p = 0.012). Conclusion: Infection with mixed CMV genotypes was common and multiple gB, gN, and gO genotypes were associated with clinical manifestation and higher viral load.

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“…The CMV disease in kidney and liver transplant recipients is associated with an elevated rate of viral load and viral load peak [8]. CMV UL55 gene encodes for a glycoprotein B which involved in several essential steps in CMV virus pathogenesis including virus penetration into cells, cell-to-cell spread, and activation of the immune response gB [9] and is involved in the activation of innate immunity as the major antigen for the induction of neutralizing antibodies. gB antibodies have been of interest because of their therapeutic potential for neutralization [10].…”

Section: Introductionmentioning

confidence: 99%

“…gB antibodies have been of interest because of their therapeutic potential for neutralization [10]. Regarding UL55 polymorphism, CMV has been divided into 4 genotypes (gB1-4) [9]. A fifth gB genotype (gB5) was detected in several AIDS patients [11].…”

Section: Introductionmentioning

confidence: 99%

Molecular Detection and Glycoprotein B (UL55) Genotyping of Cytomegalovirus among Sudanese Renal Transplant Recipients

Ahmed

Omer

Altyab

2019

Preprint

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Background Cytomegalovirus (CMV) is the most common opportunistic pathogen among solid organ transplant recipients’ especially renal transplants with significant morbidity and mortality. This study was designed to detect CMV DNA and to determine the frequency of different glycoprotein B (UL55) genotypes among Sudanese renal transplant recipients. Methods One hundred and four renal transplant recipients were included in this study. A blood specimen was collected from each recipient. DNA was extracted from plasma using QIAamp DNA mini kit. CMV amplification and quantification (estimation of viral load) was performed using CMV Real – RT Quant kits. Genotyping of Human CMV gB was carried out by nested PCR and sequencing of the highly diverse region of glycoprotein B. Results Cytomegalovirus (CMV) DNA (viremia) was detected in 40/104 (38.5%) of renal transplant recipients. The average of CMV DNA viral load was 358 x104 copies/ml (6.5 log10) ranged from 62 copies/ml (1.8 log 10) to 1.43x108 copies/ml (9 log10). CMV viremia was detected in (60%) of recipients of less than 1-12 months, (17%) of 13-24, (10%) of 25-36, (5%) of 37- 48 and (8%) in more than 48 months post-transplantation with no significant association (P. value = 0.296) between CMV viremia and post renal transplantation time. The association between the type of immunosuppressive drugs and high viral loads (more than 1000 copies /ml) showed a significant difference (P. value =0.05). The correlation between CMV loads of more than 1000 copies/ml and the presence of symptoms of CMV disease were highly significant (P.value =0.00). Fever 7(41%), fever and leucopenia 6(35%) and gastrointestinal disease 4(24%) were the most common presenting symptoms of CMV disease. CMV-genotyping revealed 8 cases (80%) for gB3, and 2 cases (20%) for gB4 genotypes. The most frequent genotype among Sudanese renal transplant recipients was gB3 and no mixed genotypes were observed. Conclusions The frequency of CMV DNA is high among Sudanese renal transplant recipients. CMV viremia viral loads were slightly lower in asymptomatic patients. CMV gB3 is the most predominant glycoprotein B genotype in Sudanese renal transplant recipients.

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Cytomegalovirus Glycoprotein B Genotype Distribution in Italian Transplant Patients

Cited by 13 publications

References 14 publications

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

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

Cytomegalovirus Glycoprotein Polymorphisms and Increasing Viral Load in Non-Transplant Patients with Hematological Malignancies Undergoing Chemotherapy: A Prospective Observational Study

Molecular Detection and Glycoprotein B (UL55) Genotyping of Cytomegalovirus among Sudanese Renal Transplant Recipients

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