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Can we build it better? Using BAC genetics to engineer more effective cytomegalovirus vaccines
Mark R. Schleiss
Mark R. Schleiss
Published November 22, 2010
Citation Information: J Clin Invest. 2010;120(12):4192-4197. https://doi.org/10.1172/JCI45250.
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Commentary

Can we build it better? Using BAC genetics to engineer more effective cytomegalovirus vaccines

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Abstract

The magnitude and durability of immunity to human cytomegalovirus (HCMV) following natural infection is compromised by the presence of immune modulation genes that appear to promote evasion of host clearance mechanisms. Since immunity to HCMV offers limited protection, rational design of effective vaccines has been challenging. In this issue of the JCI, Slavuljica and colleagues employ techniques to genetically modify the highly related mouse CMV (MCMV), in the process generating a virus that was rapidly cleared by NK cells. The virus functioned as a safe and highly effective vaccine. Demonstration of the ability to engineer a safe and highly effective live virus vaccine in a relevant rodent model of CMV infection may open the door to clinical trials of safer and more immunogenic HCMV vaccines.

Authors

Mark R. Schleiss

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Figure 1

Impact of HCMV gene products on NK cell–mediated pathways of inhibition and activation.

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Impact of HCMV gene products on NK cell–mediated pathways of inhibition ...
(A) Receptor-ligand interactions modulating NK cell function. MHC class I interacts with the inhibitory receptor LIR-1, and HLA-E interacts with the CD94/NKG2A receptor; both interactions result in inhibition of NK cell function. The ligands MICA, ULBP1/2, and MICB all interact with the NKG2D receptor, resulting in NK cell activation. (B) HCMV genes encode proteins that modify NK cell responses. NK cell evasion can be mediated by the HCMV UL18 gene product (gpUL18), a ligand for the inhibitory receptor LIR-1; the UL16 gene product (gpUL16), which downregulates the NKG2D activating ligands MICB and ULBP1/2; the UL142 gene product (gpUL142), which downregulates the NKG2D ligand MICA; an epitope from the leader peptide segment of the UL40-encoded protein, which loads HLA-E, driving an inhibitory signal to the NK cell via the CD94/NKG2A receptor; and a miRNA from the UL112 gene, which interacts with a cellular miRNA to inhibit MICB expression by preventing translation of MICB mRNA.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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