HCMV gB genotype and its association with cytokine levels in hematopoietic stem cell transplantation

Correia-Silva, Jeane F.; Resende, Renata Gonçalves; Arão, Telma Cristina; Abreu, Mauro Henrique Nogueira Guimarães de; Teixeira, Mauro M.; Bittencourt, Henrique; Silva, T A; Gomez, Ricardo Santiago

doi:10.1111/j.1601-0825.2011.01801.x

Cited by 9 publications

(8 citation statements)

References 34 publications

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“…Among viral factors, genetic variability has been analyzed in order to determine the possible association between viral genetic features and infection outcome; several genes have been targeted for evaluation including those encoding for gB, glycoprotein N, glycoprotein O, and the UL144 gene, among others [6,11,12,13,14]. The gB gene has been studied in different risk groups, including both solid organ and hemopoietic transplant patients [5,15,16,17,18,19,20,21,22,23,24,25,26,27], HIV-infected patients [4,6,15,16,28,29,30,31,32,33], infants with congenital infection [3] and healthy subjects [34]. So far, studies directed towards assessing the impact of genotype features on disease have yielded conflicting results.…”

Section: Discussionmentioning

confidence: 99%

“…So far, studies directed towards assessing the impact of genotype features on disease have yielded conflicting results. Nevertheless, it appears that in certain circumstances strain type may have a role in the occurrence of CMV disease; for instance, most studies in HIV-positive patients report gB2 as the most common genotype [4,6,15,16,28,29,30,31,32,33], while in transplant patients gB1 is the predominant genotype [5,15,16,17,18,19,20,21,22,23,24,25,26,27]. Also, the interpretation of these results is affected by the frequent detection of coinfections with two or more CMV strains in immunosuppressed patients [22,33].…”

Section: Discussionmentioning

confidence: 99%

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Cytomegalovirus Glycoprotein B Genotypes in Mexican Children and Women

et al. 2015

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Objective: Cytomegalovirus (CMV) is widely distributed and constitutes the main cause of congenital infections worldwide. CMV transmission during pregnancy represents one of the major impacts of this virus on public health. This study aimed at assessing glycoprotein B (gB) CMV genotypes in Mexican children and pregnant women, since there is limited information regarding CMV genomic diversity in Mexico. Methods: We analyzed CMV strains detected in Mexican children (n = 38) and women (n = 38) between 2001 and 2012. A fragment of the gB gene was amplified and sequenced, and genotypes were defined based on prototype sequences. Results: The gB1 genotype was detected more frequently in children (68.4%) compared to women (31.6%; p = 0.0028), while genotype 2 was more common in women (65.8%) compared to children (26.3%, p = 0.0012). Genotype 3 was uncommon in both groups (5.3 and 2.6%). Nucleotide sequences exhibited a high degree of similarity to prototype strains. However, we identified 17 distinct sequences that resulted in changes in the encoded amino acid sequence in four strains. Conclusions: gB1 and gB2 are the most common strains associated with CMV infection in Mexican children and women. In addition, we found that the frequency for each genotype differed amongst them, possibly due to variability in transmission or reactivation dynamics.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Cytomegalovirus Glycoprotein B Genotypes in Mexican Children and Women

et al. 2015

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“…These findings have spiked the interest of clinical virologists in identifying potential correlations between genetic variants and the pathogenic potential of different isolates. Several studies have found some evidence to correlate specific genotypes with disease outcome, investigating polymorphisms in the UL55 (glycoprotein B) (16)(17)(18)(19), UL73 (glycoprotein N) (20)(21)(22), UL75 (glycoprotein H) (23), UL144 (tumor necrosis factor alpha [TNF-␣]-like receptor) (24)(25)(26), and UL146 and UL147 (viral CXCL chemokines) (27,28) genes. Others, however, found no evidence of these relationships (29)(30)(31)(32).…”

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confidence: 99%

High-Throughput Analysis of Human Cytomegalovirus Genome Diversity Highlights the Widespread Occurrence of Gene-Disrupting Mutations and Pervasive Recombination

Sijmons

Thys

Ngwese

et al. 2015

J Virol

159

219

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Human cytomegalovirus is a widespread pathogen of major medical importance. It causes significant morbidity and mortality in immunocompromised individuals, and congenital infections can result in severe disabilities or stillbirth. Development of a vaccine is prioritized, but no candidate is close to release. Although correlations of viral genetic variability with pathogenicity are suspected, knowledge about the strain diversity of the 235-kb genome is still limited. In this study, 96 full-length human cytomegalovirus genomes from clinical isolates were characterized, quadrupling the amount of information available for full-genome analysis. These data provide the first high-resolution map of human cytomegalovirus interhost diversity and evolution. We show that cytomegalovirus is significantly more divergent than all other human herpesviruses and highlight hot spots of diversity in the genome. Importantly, 75% of strains are not genetically intact but contain disruptive mutations in a diverse set of 26 genes, including the immunomodulatory genes UL40 and UL111A. These mutants are independent of culture passage artifacts and circulate in natural populations. Pervasive recombination, which is linked to the widespread occurrence of multiple infections, was found throughout the genome. The recombination density was significantly higher than those of other human herpesviruses and correlated with strain diversity. While the overall effects of strong purifying selection on virus evolution are apparent, evidence of diversifying selection was found in several genes encoding proteins that interact with the host immune system, including UL18, UL40, UL142, and UL147. These residues may present phylogenetic signatures of past and ongoing virus-host interactions. IMPORTANCEHuman cytomegalovirus has the largest genome of all viruses that infect humans. Currently, there is a great interest in establishing associations between genetic variants and strain pathogenicity of this herpesvirus. Since the number of publicly available full-genome sequences is limited, knowledge about strain diversity is highly fragmented and biased toward a small set of loci. Combined with our previous work, we have now contributed 101 complete genome sequences. We have used these data to conduct the first high-resolution analysis of interhost genome diversity, providing an unbiased and comprehensive overview of cytomegalovirus variability. These data are of major value to the development of novel antivirals and a vaccine and to identify potential targets for genotype-phenotype experiments. Furthermore, these data have enabled a thorough study of the evolutionary processes that have shaped cytomegalovirus diversity. Human cytomegalovirus (HCMV), the prototype member of the herpesvirus subfamily Betaherpesvirinae, is a widespread and important pathogen. Seroprevalence in the adult population ranges from 45% to 100% (1). After primary infection, HCMV establishes a lifelong, latent infection in myeloid progenitor cells (2). This virus causes mild to ...

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“…Variation in gB has been used to classify HCMV genotypically, and may influence the clinical outcome (21,22), probably by affecting the cell and organ tropism of HCMV (23), the virulence of different strains (24), and host lymphocyte subpopulations and cytokine levels (25). In contrast, a lack of correlation between gB types and clinical outcomes (26-28) or a response to therapy (29) has also been reported.…”

Section: Discussionmentioning

confidence: 99%

“…Frequent intragenic variation in gB and infection with multiple gB subtypes have rendered breakthroughs in the diagnosis, treatment, or prevention of HCMV infection problematic. Moreover, reinfection and multiple infections with HCMV gB subtypes occur, and this is thought to result in an unfavorable prognosis (25,30). An ELISA (31) has been reported to detect strain-specific antibody responses using recombinant antigens based on polymorphic antibody binding sites in gH (glycoprotein H) and gB from the Towne and AD169 strains.…”

Section: Discussionmentioning

confidence: 99%

Development of two potential diagnostic monoclonal antibodies against human cytomegalovirus glycoprotein B

Fan

et al. 2012

Braz J Med Biol Res

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Human cytomegalovirus glycoprotein B (gB) represents a target for diagnosis and treatment in view of the role it plays in virus entry and spread. Nevertheless, to our knowledge, rare detection of a gB antigen has been reported in transplant patients and limited information is available about diagnostic gB monoclonal antibodies (mAbs). Our aim was to develop gB mAbs with diagnostic potential. Hydrophilic gB peptides (ST: amino acids 27-40, SH: amino acids 81-94) of favorable immunogenicity were synthesized and used to immunize BALB/c mice. Two mAbs, named ZJU-FH6 and ZJU-FE6, were generated by the hybridoma technique and limited serial dilution and then characterized by indirect ELISA, Western blotting, immunoprecipitation, and immunohistochemical staining. The mAbs displayed high titers of specific binding affinities for the ST and SH synthetic peptides at an mAb dilution of 1:60,000 and 1:240,000, respectively. Western blotting and immunoprecipitation indicated that these mAbs recognized both denatured and native gB of the Towne and AD169 strains. The mAbs, when used as the primary antibody, showed positive staining in cells infected with both Towne and AD169 strains. The mAbs were then tested on patients submitted to allogeneic hematopoietic stem cell transplantation. The gB antigen positivity rates of the patients tested using ZJU-FH6 and ZJU-FE6 were 62.0 and 63.0%, respectively. The gB antigen showed a significant correlation with the level of pp65 antigen in peripheral blood leukocytes. In conclusion, two potential diagnostic gB mAbs were developed and were shown to be capable of recognizing gB in peripheral blood leukocytes in a reliable manner.

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HCMV gB genotype and its association with cytokine levels in hematopoietic stem cell transplantation

Abstract: Decreased IL-1β and increased IL-10 levels in the blood are associated with lower survival. HCMV genotypes are associated with different cytokine levels in saliva and blood.

Cited by 9 publications

References 34 publications

Cytomegalovirus Glycoprotein B Genotypes in Mexican Children and Women

Cytomegalovirus Glycoprotein B Genotypes in Mexican Children and Women

High-Throughput Analysis of Human Cytomegalovirus Genome Diversity Highlights the Widespread Occurrence of Gene-Disrupting Mutations and Pervasive Recombination

Development of two potential diagnostic monoclonal antibodies against human cytomegalovirus glycoprotein B

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