Abstract
Murid herpesvirus-4 (MuHV-4) provides a tractable model with which to define common, conserved features of gamma-herpesvirus biology. The multi-membrane spanning glycoprotein M (gM) is one of only 4 glycoproteins that are essential for MuHV-4 lytic replication. gM binds to gN and is thought to function mainly secondary envelopment and virion egress, for which several predicted trafficking motifs in its C-terminal cytoplasmic tail could be important. We tested the contribution of the gM cytoplasmic tail to MuHV-4 lytic replication by making recombinant viruses with varying C-terminal deletions. Removing an acidic cluster and a distal YXXΦ motif altered the capsid distribution somewhat in infected cells but had little effect on virus replication, either in vitro or in vivo. In contrast, removing a proximal YXXΦ motif as well completely prevented productive replication. gM was still expressed, but unlike its longer forms showed only limited colocalization with co-transfected gN, and in the context of whole virus appeared to support gN expression less well. We conclude that some elements of the gM cytoplasmic tail are dispensible for MuHV-4 replication, but the tail as a whole is not.
Highlights
Herpesviruses lytic gene functions have been studied mainly with neurotropic alpha-herpesviruses
This reflects that Epstein-Barr virus (EBV) and the Kaposi’s Sarcoma-associated Herpesvirus (KSHV) - the two known human gamma-herpesviruses - are difficult to propagate lytically in vitro and have narrow species tropisms that largely preclude their analysis in vivo
A well-established small animal model of gamma-herpesvirus infection is provided by Murid Herpesvirus-4 (MuHV-4), a rhadinovirus closely related to KSHV [1,2]
Summary
Herpesviruses lytic gene functions have been studied mainly with neurotropic alpha-herpesviruses. Little is known about the lytic replication of lymphotropic gamma-herpesviruses. This reflects that Epstein-Barr virus (EBV) and the Kaposi’s Sarcoma-associated Herpesvirus (KSHV) - the two known human gamma-herpesviruses - are difficult to propagate lytically in vitro and have narrow species tropisms that largely preclude their analysis in vivo. The main natural host for MuHV-4 is yellow-necked mice [4] It appears to have quite a broad tropism [1] and behaves much like a natural pathogen in inbred laboratory mouse strains [5,6]. Some 90% of MuHV-4 genes have obvious equivalents in KSHV and EBV [9] This is true of lytic genes; latency-associated genes are less well conserved. The complement of essential MuHV-4 glycoproteins is surprisingly small: only gH, gB, gN and gM [10,11,12] are essential; gp70 [13,14], gp48 [15], ORF28 [16], ORF58 [17], gL [18], gp150 [19] and ORF74 [20,21] are not
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