How Kaposi's sarcoma-associated herpesvirus stably transforms peripheral B cells towards lymphomagenesis.
B-Lymphocytes
/ virology
CD40 Ligand
/ metabolism
Carcinogenesis
/ immunology
Cell Proliferation
Cell Transformation, Neoplastic
/ pathology
Gene Expression Regulation, Viral
Green Fluorescent Proteins
/ metabolism
Herpesvirus 4, Human
/ physiology
Herpesvirus 8, Human
/ genetics
Humans
Interleukin-4
/ metabolism
Lymphocyte Activation
/ immunology
Lymphoma
/ pathology
Sarcoma, Kaposi
/ immunology
EBV
KSHV
in vitro transformation
primary effusion lymphoma
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
13 08 2019
13 08 2019
Historique:
pubmed:
1
8
2019
medline:
26
3
2020
entrez:
1
8
2019
Statut:
ppublish
Résumé
Primary effusion lymphomas (PELs) are causally associated with Kaposi's sarcoma-associated herpesvirus (KSHV) and 86% of PELs are coinfected with Epstein-Barr virus (EBV). Understanding how PELs develop has been impaired by the difficulty of infecting B cells with KSHV in vitro, and the inability of KSHV to transform them. We show that EBV supports an optimal coinfection of 2.5% of peripheral B cells by KSHV. This coinfection requires 1 or more transforming genes of EBV but not entry into KSHV's lytic cycle. We demonstrate that dually infected B cells are stably transformed in vitro and show that while both viruses can be maintained, different cells exhibit distinct, transformed properties. Transformed cells that grow to predominate in a culture express increased levels of most KSHV genes and differentially express a subset of cellular genes, as do bona fide PEL cells. These dually infected peripheral B cells are thus both stably transformed and allow in vitro molecular dissection of early steps in the progression to lymphomagenesis.
Identifiants
pubmed: 31363046
pii: 1905025116
doi: 10.1073/pnas.1905025116
pmc: PMC6697783
doi:
Substances chimiques
CD40 Ligand
147205-72-9
Green Fluorescent Proteins
147336-22-9
Interleukin-4
207137-56-2
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
16519-16528Subventions
Organisme : NCI NIH HHS
ID : P01 CA022443
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA014520
Pays : United States
Organisme : NIH HHS
ID : S10 OD018202
Pays : United States
Informations de copyright
Copyright © 2019 the Author(s). Published by PNAS.
Déclaration de conflit d'intérêts
The authors declare no conflict of interest.
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