Principles for studying in vivo attenuation of virus mutants: defining the role of the cytomegalovirus gH/gL/gO complex as a paradigm

Medical Microbiology and Immunology
Jürgen PodlechNiels A W Lemmermann

Abstract

Initial virus entry into cells of host organs and subsequent spread of viral progeny between tissue cells are events fundamental to viral pathogenesis. Glycoprotein complexes inserted in the virion envelope are critically involved in the cell entry process. Here we review and discuss recent work that has shed light on the in vivo role of the trimeric glycoprotein complex gH/gL/gO of murine cytomegalovirus (mCMV) as a model to propose the role of the corresponding complex of human CMV, for which experimental studies in vivo are not feasible due to the host species specificity of CMVs and evident ethical constraints. A novel approach combining gO transcomplementation of a genetically gO-deficient virus and a mathematical log-linear regression analysis of the viral multiplication kinetics in host tissues revealed a critical role of mCMV gH/gL/gO only in first target cell entry of virions arriving with the circulation, whereas intra-tissue spread proceeded unaffected also in the absence of gH/gL/gO. These findings predict that targeting gO for an antiviral intervention may be of prophylactic value in preventing the seeding of virus to organs, but will likely fail to interfere with an established primary organ infection or with recu...Continue Reading

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Citations

Jul 17, 2015·PLoS Pathogens·Simone ThomasNiels A W Lemmermann
Nov 4, 2016·Medical Microbiology and Immunology·Bodo Plachter
Oct 3, 2018·Proceedings of the National Academy of Sciences of the United States of America·Kai WuThomas Shenk
Mar 30, 2019·Medical Microbiology and Immunology·Astrid KrmpotićStipan Jonjić

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