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HCMV envelope glycoprotein diversity demystified

  • Foglierini, Mathilde Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland - Swiss Institute of Bioinformatics, Lausanne, Switzerland
  • Marcandalli, Jessica Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • Perez, Laurent Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
    15.05.2019
Published in:
  • Frontiers in microbiology. - 2019, vol. 10, p. 1005
Human cytomegalovirus
Envelope glycoproteins
Viral diversity
Multiple sequence alignment
Protein sequence analysis
Phylogenic analysis
English Human cytomegalovirus (HCMV) is the leading viral cause of congenital birth defects and is responsible for morbidity and mortality in immunosuppressed individuals. Considerable efforts have been deployed over the last decade to develop a vaccine capable of preventing HCMV infection. However, in recent clinical trials, vaccines showed at best modest efficacy in preventing infection. These findings might be explained by the high level of sequence polymorphism at the genomic level. To investigate if genomic variation also leads to antigenic variation, we performed a bioinformatic sequence analysis and evaluated the percentage of conservation at the amino acid level of all the proteins present in the virion envelope. Using more than two hundred sequences per envelope glycoprotein and analyzing their degree of conservation, we observe that antigenic variation is in large part limited to three proteins. In addition, we demonstrate that the two leading vaccine candidates, the pentamer and gB complexes, are well conserved at the amino acid level. These results suggest that despite genomic polymorphism, antigenic variability is not involved in the modest efficacy observed in the recent clinical trials for a HCMV vaccine. We therefore propose that next-generation vaccines should focus on stabilizing and refining the gB domains needed to induce a protective humoral response.
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  • English
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Pathology, clinical medicine
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https://n2t.net/ark:/12658/srd1319128
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