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Role of Envelope Glycoprotein Complexes in Cell-Associated Spread of Human Cytomegalovirus

Nina Weiler1, Caroline Paal1, Kerstin Adams1

  • 1Institute for Virology, Ulm University Medical Center, 89089 Ulm, Germany.

Viruses
|April 30, 2021
PubMed

Insights

Viral envelope glycoproteins are crucial for human cytomegalovirus (HCMV) spread. Accessory proteins in trimeric and pentameric gH/gL-complexes influence cell-associated transmission, with pentameric complex downregulation releasing infectious virus.

Area of Science:

  • Virology
  • Molecular Biology
  • Cell Biology

Background:

  • The role of viral envelope glycoproteins in human cytomegalovirus (HCMV) cell-associated spread remains incompletely understood.
  • Accessory proteins within trimeric and pentameric gH/gL-complexes are key viral surface components.

Purpose of the Study:

  • To investigate the contribution of viral envelope glycoproteins, specifically accessory proteins of gH/gL-complexes, to HCMV cell-associated spread.
  • To analyze HCMV variants that exhibit strictly cell-associated growth patterns.

Main Methods:

  • Deletion of essential glycoproteins (gB, gH, gL, gM, gN) in the Merlin pAL1502 HCMV strain to assess viral growth.
  • Quantitative immunoblotting to compare expression levels of gO and pUL128 accessory proteins in Merlin and recent HCMV isolates.
  • siRNA-mediated knockdown of gO and pUL128 to evaluate effects on viral focal growth and infectious virus release.

Main Results:

  • All five deleted glycoproteins were essential for Merlin pAL1502 growth.
  • Recent HCMV isolates showed higher gO levels compared to the model virus; gO knockdown reduced viral growth.
  • pUL128 knockdown disrupted strict cell-association, leading to infectious virus release and subsequent cell-free transfer to epithelial cells.

Conclusions:

  • Both trimeric and pentameric gH/gL-complexes contribute to the cell-associated spread of recent clinical HCMV isolates.
  • Downregulation of the pentameric complex (pUL128) can result in the release of infectious virus into the supernatant, potentially facilitating broader transmission.
Keywords:
cell-associated spreadclinical isolatescytomegalovirusglycoproteinspentamertrimer

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