Viral and Cellular Factors Contributing to the Hematogenous Dissemination of Human Cytomegalovirus via Polymorphonuclear Leukocytes.
clinical isolates
entry inhibitors
hematogenous dissemination
herpesvirus entry
human cytomegalovirus
Journal
Viruses
ISSN: 1999-4915
Titre abrégé: Viruses
Pays: Switzerland
ID NLM: 101509722
Informations de publication
Date de publication:
18 07 2022
18 07 2022
Historique:
received:
06
05
2022
revised:
12
07
2022
accepted:
16
07
2022
entrez:
27
7
2022
pubmed:
28
7
2022
medline:
29
7
2022
Statut:
epublish
Résumé
Polymorphonuclear leukocytes (PMNs) presumably transmit human cytomegalovirus (HCMV) between endothelial cells in blood vessels and thereby facilitate spread to peripheral organs. We aimed to identify viral components that contribute to PMN-mediated transmission and test the hypothesis that cellular adhesion molecules shield transmission sites from entry inhibitors. Stop codons were introduced into the genome of HCMV strain Merlin to delete pUL74 of the trimeric and pUL128 of the pentameric glycoprotein complex and the tegument proteins pp65 and pp71. Mutants were analyzed regarding virus uptake by PMNs and transfer of infection to endothelial cells. Cellular adhesion molecules were evaluated for their contribution to virus transmission using function-blocking antibodies, and hits were further analyzed regarding shielding against inhibitors of virus entry. The viral proteins pUL128, pp65, and pp71 were required for efficient PMN-mediated transmission, whereas pUL74 was dispensable. On the cellular side, the blocking of the αLβ2-integrin LFA-1 reduced virus transfer by 50% and allowed entry inhibitors to reduce it further by 30%. In conclusion, these data show that PMN-mediated transmission depends on the pentameric complex and an intact tegument and supports the idea of a virological synapse that promotes this dissemination mode both directly and via immune evasion.
Identifiants
pubmed: 35891541
pii: v14071561
doi: 10.3390/v14071561
pmc: PMC9323586
pii:
doi:
Substances chimiques
Viral Envelope Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
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