title: Toll-like receptor 4 is involved in the cell cycle modulation and required for effective human cytomegalovirus infection in THP-1 macrophages.
abstract: Suitable host cell metabolic conditions are fundamental for the effective development of the human cytomegalovirus (HCMV) lytic cycle. Indeed, several studies have demonstrated the ability of this virus to interfere with cell cycle regulation, mainly by blocking proliferating cells in G1 or G1/S. In the present study, we demonstrate that HCMV deregulates the cell cycle of THP-1 macrophages (a cell line irreversibly arrested in G0) by pushing them into S and G2 phases. Moreover, we show that HCMV infection of THP-1 macrophages leads to Toll-like receptor 4 (TLR4) activation. Since various studies have indicated TLR4 to be involved in promoting cell proliferation, here we investigate the possible role of TLR4 in the observed HCMV-induced cell cycle perturbation. Our data strongly support TLR4 as a mediator of HCMV-triggered cell cycle activation in THP-1 macrophages favouring, in turn, the development of an efficient viral lytic cycle.
authors.affiliation: Department of Clinical and Experimental Medicine, University of Parma, Parma, Italy. mariacristina.arcangeletti@unipr.it
authors.forename: Maria-Cristina
authors.initials: MC
authors.lastname: Arcangeletti
authors.forename: Diego
authors.initials: D
authors.lastname: Germini
authors.forename: Isabella
authors.initials: I
authors.lastname: Rodighiero
authors.forename: Prisco
authors.initials: P
authors.lastname: Mirandola
authors.forename: Flora
authors.initials: F
authors.lastname: De Conto
authors.forename: Maria-Cristina
authors.initials: MC
authors.lastname: Medici
authors.forename: Rita
authors.initials: R
authors.lastname: Gatti
authors.forename: Carlo
authors.initials: C
authors.lastname: Chezzi
authors.forename: Adriana
authors.initials: A
authors.lastname: Calderaro
mesh_terms: D002453:Cell Cycle / Q000502:physiology*; D002460:Cell Line; D003587:Cytomegalovirus / Q000502:physiology* / Q000528:radiation effects; D005786:Gene Expression Regulation; D006801:Humans; D016899:Interferon-beta / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000166:cytology* / Q000821:virology*; D051197:Toll-Like Receptor 4 / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D014466:Ultraviolet Rays; D014779:Virus Replication / Q000502:physiology*
chemical_list: C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D016899:Interferon-beta