Abstract:
:Nectin-1 and nectin-2 are related molecules that can function with different specificities as entry receptors for mammalian alphaherpesviruses through interaction with viral glycoprotein D (gD). The normal function of members of the nectin family is to mediate cell-cell adhesion through homotypic and heterotypic nectin-nectin interactions in cadherin-based adherens junctions. We examined mutations in three equivalent regions of the N-terminal V-like domains of nectin-1 and nectin-2 to test the effects on entry of various alphaherpesviruses, nectin-nectin interactions, and interactions of the mutant nectins with gD. Mutations in region I previously shown to severely impair herpes simplex virus (HSV) entry activity, but not pseudorabies virus (PRV) or bovine herpesvirus 1 (BHV-1) entry, did not reduce homotypic trans interactions for either nectin-1 or nectin-2 or binding of nectin-3 to nectin-1. Mutations in region II, patterned after a reported single-nucleotide polymorphism in nectin-2, enhanced intracellular accumulation of both nectin-1 and nectin-2 and had a deleterious effect on all of the activities under study. Mutations in region III previously shown to reduce homotypic trans interactions of nectin-2 impaired the entry of PRV and BHV-1 when introduced into either nectin-1 or nectin-2, but only the nectin-2 mutation reduced HSV entry activity. Binding of nectin-1 to nectin-3 was not affected. Effects of the nectin-1 and nectin-2 mutations on interactions with gD did not necessarily correlate with entry activity of the mutant receptors. We can conclude that structural requirements for HSV entry, PRV and BHV-1 entry, and homotypic and heterotypic trans interactions are all different despite the previously reported ability of HSV and HSV gD to inhibit trans interactions.
journal_name
J Viroljournal_title
Journal of virologyauthors
Struyf F,Martinez WM,Spear PGdoi
10.1128/jvi.76.24.12940-12950.2002subject
Has Abstractpub_date
2002-12-01 00:00:00pages
12940-50issue
24eissn
0022-538Xissn
1098-5514journal_volume
76pub_type
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.75.6.2575-2583.2001
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pub_type: 杂志文章
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更新日期:2004-10-01 00:00:00
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pub_type: 杂志文章
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journal_title:Journal of virology
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/jvi.77.12.6601-6612.2003
更新日期:2003-06-01 00:00:00
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journal_title:Journal of virology
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journal_title:Journal of virology
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journal_title:Journal of virology
pub_type: 杂志文章
doi:10.1128/JVI.68.12.8001-8007.1994
更新日期:1994-12-01 00:00:00
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pub_type: 杂志文章,评审
doi:10.1128/JVI.01357-19
更新日期:2020-01-31 00:00:00