Glycoprotein B cleavage is important for murid herpesvirus 4 to infect myeloid cells.

Abstract:

:Glycoprotein B (gB) is a conserved herpesvirus virion component implicated in membrane fusion. As with many-but not all-herpesviruses, the gB of murid herpesvirus 4 (MuHV-4) is cleaved into disulfide-linked subunits, apparently by furin. Preventing gB cleavage for some herpesviruses causes minor infection deficits in vitro, but what the cleavage contributes to host colonization has been unclear. To address this, we mutated the furin cleavage site (R-R-K-R) of the MuHV-4 gB. Abolishing gB cleavage did not affect its expression levels, glycosylation, or antigenic conformation. In vitro, mutant viruses entered fibroblasts and epithelial cells normally but had a significant entry deficit in myeloid cells such as macrophages and bone marrow-derived dendritic cells. The deficit in myeloid cells was not due to reduced virion binding or endocytosis, suggesting that gB cleavage promotes infection at a postendocytic entry step, presumably viral membrane fusion. In vivo, viruses lacking gB cleavage showed reduced lytic spread in the lungs. Alveolar epithelial cell infection was normal, but alveolar macrophage infection was significantly reduced. Normal long-term latency in lymphoid tissue was established nonetheless.

journal_name

J Virol

journal_title

Journal of virology

authors

Glauser DL,Milho R,Frederico B,May JS,Kratz AS,Gillet L,Stevenson PG

doi

10.1128/JVI.00709-13

subject

Has Abstract

pub_date

2013-10-01 00:00:00

pages

10828-42

issue

19

eissn

0022-538X

issn

1098-5514

pii

JVI.00709-13

journal_volume

87

pub_type

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