Human cytomegalovirus UL130 protein promotes endothelial cell infection through a producer cell modification of the virion

Marco Patrone, Massimiliano Secchi, Loretta Fiorina, Mariagrazia Ierardi, Gabriele Milanesi, Andrea Gallina

Research output: Contribution to journalArticle

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Abstract

Human cytomegalovirus (HCMV) growth in endothelial cells (EC) requires the expression of the UL131A-128 locus proteins. In this study, the UL130 protein (pUL130), the product of the largest gene of the locus, is shown to be a luminal glycoprotein that is inefficiently secreted from infected cells but is incorporated into the virion envelope as a Golgi-matured form. To investigate the mechanism of the UL130-mediated promotion of viral growth in EC, we performed a complementation analysis of a UL130 mutant strain. To provide UL130 in trans to viral infections, we constructed human embryonic lung fibroblast (HELF) and human umbilical vein endothelial cell (HUVEC) derivative cell lines that express UL130 via a retroviral vector. When the UL130-negative virus was grown in UL130-complementing HELF, the infectivity of progeny virions for HUVEC was restored to the wild-type level. In contrast, the infectivity of the UL130-negative virus for UL130-complementing HUVEC was low and similar to that of the same virus infecting control noncomplementing HUVEC. The UL130-negative virus, regardless of whether or not it had been complemented in the prior cycle, could form plaques only on UL130-complementing HUVEC, not control HUVEC. Because (i) both wild-type and UL130-transcomplemented virions maintained their infectivity for HUVEC after purification, (ii) UL130 failed to complement in trans the UL130-negative virus when it was synthesized in a cell separate from the one that produced the virions, and (iii) pUL130 is a virion protein, models are favored in which pUL130 acquisition in the producer cell renders HCMV virions competent for a subsequent infection of EC.

Original languageEnglish
Pages (from-to)8361-8373
Number of pages13
JournalJournal of Virology
Volume79
Issue number13
DOIs
Publication statusPublished - Jul 2005

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Human herpesvirus 5
Human Umbilical Vein Endothelial Cells
virion
Virion
endothelial cells
Endothelial Cells
Infection
Viruses
infection
viruses
proteins
cells
pathogenicity
Cytomegalovirus
fibroblasts
Fibroblasts
lungs
retroviral vectors
Lung
loci

ASJC Scopus subject areas

  • Immunology

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Human cytomegalovirus UL130 protein promotes endothelial cell infection through a producer cell modification of the virion. / Patrone, Marco; Secchi, Massimiliano; Fiorina, Loretta; Ierardi, Mariagrazia; Milanesi, Gabriele; Gallina, Andrea.

In: Journal of Virology, Vol. 79, No. 13, 07.2005, p. 8361-8373.

Research output: Contribution to journalArticle

Patrone, Marco ; Secchi, Massimiliano ; Fiorina, Loretta ; Ierardi, Mariagrazia ; Milanesi, Gabriele ; Gallina, Andrea. / Human cytomegalovirus UL130 protein promotes endothelial cell infection through a producer cell modification of the virion. In: Journal of Virology. 2005 ; Vol. 79, No. 13. pp. 8361-8373.
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