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Title: Genomic variants of human cytomegalovirus RL13
Authors: Sijmons, Steven
Corthout, Michaël
Van Ranst, Marc
Maes, Piet
Issue Date: 2012
Conference: Annual International Herpesvirus Workshop edition:37 location:Calgary, Canada date:4-9 August 2012
Abstract: The HCMV genome contains 12 multigene families. The RL11 family consists of 14 genes not essential for viral replication in vitro and most
of which are putative transmembrane glycoproteins. Several members show a striking interstrain genetic variability, including RL13, that has
been shown to be a virion envelope protein. RL13 is a potent inhibitor of HCMV replication in multiple cell types and came out top five in a
study measuring HCMV ORF immunogenicity for CD4+ T cells. Considering its hypervariability, one can speculate on possible differences in
RL13 impact on tropism and immunogenicity relating to different genomic variants. Regarding the paucity of RL13 sequences available, we set
out to characterize RL13 genetic diversity in 54 isolates from urine, bronchoalveolar lavage, blood and oronasopharyngeal swabs taken from
a diverse, Belgian patient population. 46 isolates were PCR amplified, the others were sequenced after passaging strains two to five times
in fibroblasts. Sequences were aligned on amino acid level and neighbor-joining trees were constructed. A clear clustering into six distinct
genotypes could be defined. Four groups contained both PCR amplified, cell culture amplified and previously published sequences. Overall
identity between genotypes was only 42% at the amino acid level. Appropriate identity cutoff values were determined via the construction
of pairwise identity frequency graphs. Different genotypes are defined by a clear cutoff value of 80% and 75%, respectively on nucleotide
and amino acid levels. Samples included serial isolates from seven patients to assess RL13 stability. For up to two years, there was no change
in RL13, so at least in our patient population, RL13 genetic variation seems to be stable. Comparison of non-synonymous to synonymous
nucleotide substitution ratios between genotypes revealed that RL13 diversity is maintained by purifying selection.
Publication status: published
KU Leuven publication type: IMa
Appears in Collections:Laboratory of Clinical and Epidemiological Virology (Rega Institute)
Department of Health and Technology - UC Leuven

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