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bioRxiv · 10.1101/2024.11.29.625639

A dual role in virion attachment and entry makes the human cytomegalovirus gHgLgO trimer the central player in virion infectivity

Thiessen, L.·Garuti, R.·Kubic, L.·Koesters, M.·Amarambedu Selvakumar, D.·Krey, T.·Goerzer, I.·Froehlich, T.·Adler, B.
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Abstract

Glycoproteins in the viral envelope of human cytomegalovirus (HCMV) orchestrate virion tethering, receptor recognition and fusion with cellular membranes. The glycoprotein gB acts as fusion protein. The gHgL complexes gHgLgO and gHgLpUL(128,130,131A) define the HCMV cell tropism. Studies with HCMV lacking gO had indicated that gO, independently of binding to its cellular receptor PDGFR, plays an important second role in infection. Here, we identified a gO mutation which abolished virus particle infectivity by preventing the interaction of gHgLgO with host cell heparan sulfate proteoglycans (HSPGs). We could not only show that gHgLgO - HSPG interactions are a genuine second role of gHgLgO, but also that gHgLgO is the main player in determining the infectivity of HCMV virus particles. This challenges long-accepted textbook knowledge on the role of gB and gMgN complexes in virion tethering. Additionally, it adds the gHgLgO complex to the antigens of interest for future HCMV vaccines or treatments.

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Thiessen, L., Garuti, R., Kubic, L., Koesters, M., Amarambedu Selvakumar, D., Krey, T., Goerzer, I., Froehlich, T., Adler, B.. 2024-11-30. A dual role in virion attachment and entry makes the human cytomegalovirus gHgLgO trimer the central player in virion infectivity. https://doi.org/10.1101/2024.11.29.625639

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