Human cytomegalovirus penetrates host cells by PH-independent fusion at the cell surface

Compton, Teresa; Nepomuceno, Ronald R.; Nowlin, Dawn M.

doi:10.1016/0042-6822(92)90200-9

Cited by 187 publications

(181 citation statements)

References 36 publications

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“…After stable attachment to the cell surface, virions undergo a pH-independent fusion event with the host cell plasma membrane (Compton et al, 1992) whereby the viral nucleocapsid is deposited in the cell cytoplasm. The events between initial binding of HCMV to HSPGs and direct fusion of the viral envelope with the plasma membrane are poorly understood, although these events probably involve multiple cellular and viral components (Compton, 1995).…”

Section: Introductionmentioning

confidence: 99%

Interference with annexin II has no effect on entry of human cytomegalovirus into fibroblast cells.

Pietropaolo¹,

Compton

1999

Journal of General Virology

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Annexin II has been identified as a human cytomegalovirus (HCMV)-binding protein, shown to be a component of purified virions and proposed as a cellular receptor for the virus. In addition, annexin II is capable of associating with the major HCMV envelope glycoprotein, gB (gpUL55). As one approach to examine the role of annexin II in virus entry, a high-titre polyclonal annexin IIspecific antibody was produced and its effects in virus entry and cell-to-cell spread assays were tested. This anti-annexin II serum recognized virion and cell surface annexin II and annexin IIderived peptides. Recombinant annexin II, with characteristic calcium-and phospholipid-binding activities, was also examined. Pretreatment of cells, virions or both with polyclonal anti-annexin II serum, affinity-purified anti-annexin II antibodies or recombinant annexin II protein prior to infection was inconsequential to the entry of HCMV into fibroblasts. HCMV was also able to dosedependently penetrate annexin II-deficient 293 cells. Furthermore, the spread of HCMV from cell to cell was not inhibited in the presence of polyclonal anti-annexin II antibodies or exogenous annexin II protein. These experiments do not support a direct role of annexin II in virus entry or spread. Alternative roles for the gB-annexin II interaction are proposed.

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Section: Introductionmentioning

confidence: 99%

Interference with annexin II has no effect on entry of human cytomegalovirus into fibroblast cells.

Pietropaolo¹,

Compton

1999

Journal of General Virology

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“…Viral glycoproteins play important roles in virus attachment to susceptible cells, fusion of the viral envelope with either cellular or endosomal membranes, and virion morphogenesis and egress (reviewed in references 25, 31, and 47). Herpes simplex virus, human cytomegalovirus, and EpsteinBarr virus (EBV) have been shown to enter cells by either pH-independent or pH-dependent pathways, depending on the cell type (8,13,30,37,41,47,51). KSHV has been shown to enter certain cells (human foreskin fibroblast cells and B cells) by endocytosis (1,4).…”

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Kaposi's Sarcoma-Associated Herpesvirus Glycoprotein K8.1 Is Dispensable for Virus Entry

Luna

Zhou

Baghian³

et al. 2004

J Virol

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“…HCMV entry into fibroblasts is mediated by the gH/gL/gO complex at the cell surface at neutral pH (18)(19)(20)(21). gO is a highly glycosylated protein and has been shown to covalently interact with gH/gL (22,23).…”

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confidence: 99%

Structural and biochemical studies of HCMV gH/gL/gO and Pentamer reveal mutually exclusive cell entry complexes

Ciferri

Chandramouli

Donnarumma

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

138

189

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Human cytomegalovirus (HCMV) is a major cause of morbidity and mortality in transplant patients and the leading viral cause of birth defects after congenital infection. The glycoprotein complexes gH/gL/gO and gH/gL/UL128/UL130/UL131A (Pentamer) are key targets of the human humoral response against HCMV and are required for HCMV entry into fibroblasts and endothelial/epithelial cells, respectively. We expressed and characterized soluble forms of gH/gL, gH/gL/gO, and Pentamer. Mass spectrometry and mutagenesis analysis revealed that gL-Cys144 forms disulfide bonds with gO-Cys351 in gH/gL/gO and with UL128-Cys162 in the Pentamer. Notably, Pentamer harboring the UL128-Cys162Ser/gL-Cys144Ser mutations had impaired syncytia formation and reduced interference of HCMV entry into epithelial cells. Electron microscopy analysis showed that HCMV gH/gL resembles HSV gH/gL and that gO and UL128/UL130/UL131A bind to the same site at the gH/gL N terminus. These data are consistent with gH/gL/gO and Pentamer forming mutually exclusive cell entry complexes and reveal the overall location of gH/gL-, gH/gL/ gO-, and Pentamer-specific neutralizing antibody binding sites. Our results provide, to our knowledge, the first structural view of gH/gL/ gO and Pentamer supporting the development of vaccines and antibody therapeutics against HCMV.human cytomegalovirus | HCMV | Pentamer complex | gH/gL/gO | virus entry

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Human cytomegalovirus penetrates host cells by PH-independent fusion at the cell surface

Cited by 187 publications

References 36 publications

Interference with annexin II has no effect on entry of human cytomegalovirus into fibroblast cells.

Interference with annexin II has no effect on entry of human cytomegalovirus into fibroblast cells.

Kaposi's Sarcoma-Associated Herpesvirus Glycoprotein K8.1 Is Dispensable for Virus Entry

Structural and biochemical studies of HCMV gH/gL/gO and Pentamer reveal mutually exclusive cell entry complexes

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