title: Divergent tropism of HHV-6AGSand HHV-6BPL1in T cells expressing different CD46 isoform patterns.
abstract: CD46 is a receptor for HHV-6A, but its role as a receptor for HHV-6B is controversial. The significance of CD46 isoforms for HHV-6A and HHV-6B tropism is unknown. HHV-6AGSwas able to initiate transcription of the viral genes U7 and U23 in the CD46+CD134-T-cell lines Peer, Jurkat, Molt3, and SupT1, whereas HHV-6BPL1was only able to do so in Molt3 and SupT1, which expressed a CD46 isoform pattern different from Peer and Jurkat. The HHV-6BPL1-susceptible T-cell lines were characterized by low expression of the CD46 isoform BC2 and domination of isoforms containing the cytoplasmic tail, CYT-1. A HHV-6BPL1susceptible cell line, Be13, changed over time its CD46 isoform pattern to resemble Peer and Jurkat and concomitantly lost its susceptibility to HHV-6BPL1but not HHV-6AGSinfection. We propose that isoforms of CD46 impact on HHV-6B infection and thereby in part explain the distinct tropism of HHV-6AGSand HHV-6BPL1.
authors.affiliation: Department of Biomedicine, Aarhus University, Bartholins Allé 6, DK-8000 Aarhus, Denmark.
authors.forename: Aida S
authors.initials: AS
authors.lastname: Hansen
authors.affiliation: Department of Biomedicine, Aarhus University, Bartholins Allé 6, DK-8000 Aarhus, Denmark.
authors.forename: Bettina B
authors.initials: BB
authors.lastname: Bundgaard
authors.affiliation: Department of Biomedicine, Aarhus University, Bartholins Allé 6, DK-8000 Aarhus, Denmark.
authors.forename: Mette
authors.initials: M
authors.lastname: Biltoft
authors.affiliation: Department of Biomedicine, Aarhus University, Bartholins Allé 6, DK-8000 Aarhus, Denmark.
authors.forename: Litten S
authors.initials: LS
authors.lastname: Rossen
authors.affiliation: Department of Biomedicine, Aarhus University, Bartholins Allé 6, DK-8000 Aarhus, Denmark. Electronic address: ph@biomed.au.dk.
authors.forename: Per
authors.initials: P
authors.lastname: Höllsberg
mesh_terms: D002460:Cell Line; D015654:Herpesvirus 6, Human / Q000145:classification / Q000235:genetics / Q000502:physiology*; D006801:Humans; D051916:Membrane Cofactor Protein / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000821:virology*; D056189:Viral Tropism; D053586:Virus Internalization
chemical_list: D051916:Membrane Cofactor Protein; D020033:Protein Isoforms; D011991:Receptors, Virus
keywords: CD46 cytoplasmic tails; CD46 splicing; Human herpesvirus 6; Isoforms; T-cell lines