A glycoprotein M-deleted equid herpesvirus 4 is severely impaired in virus egress and cell-to-cell spread

Ziegler, Christina; Just, Frank; Lischewski, A.; Elbers, Knut; Neubauer, Antonie

doi:10.1099/vir.0.80393-0

Cited by 18 publications

(14 citation statements)

References 32 publications

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“…All gN homologs investigated so far form a complex with the transmembrane (glyco)protein M (gM) (8,15,21,23,30,34,39). The gN/gM complex is implicated in such processes as maturation of virions and control of membrane fusion (31,32,40). The immune evasion properties of UL49.5 have been found in several varicelloviruses, including pseudorabies virus and equine herpesvirus 1 in addition to BHV-1 (18).…”

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confidence: 99%

Bovine Herpesvirus 1 UL49.5 Protein Inhibits the Transporter Associated with Antigen Processing despite Complex Formation with Glycoprotein M

Lipińska

Koppers-Lalić

Rychłowski

et al. 2006

J Virol

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Bovine herpesvirus 1 (BHV-1) interferes with peptide translocation by the transporter associated with antigen processing (TAP). Recently, the UL49.5 gene product of BHV-1 was identified as the protein responsible for the observed inhibition of TAP. In BHV-1-infected cells and virions, the UL49.5 protein forms a complex with glycoprotein M (gM). Hence, it was investigated whether UL49.5 can combine the interactions with gM and the TAP complex. In cell lines constitutively expressing both UL49.5 and gM, UL49.5 appears to be required for functional processing of gM. Immunofluorescence-confocal laser scanning microscopy demonstrated that both proteins are interdependent for their redistribution from the endoplasmic reticulum to the trans-Golgi network. Remarkably, expression of cloned gM results in the abrogation of the UL49.5-mediated inhibition of TAP and prevents the degradation of the transporter. However, in BHV-1-infected cells, differences in UL49.5 and gM expression kinetics were seen to create a window of opportunity at the early stages of infection, during which time the UL49.5 protein can act on TAP without gM interference. Moreover, in later periods, non-gM-associated UL49.5 can be detected in addition to the UL49.5/gM complex. Thus, it has been deduced that different functions of UL49.5, editing of gM processing and inhibition of TAP, can be combined during BHV-1 infection.

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confidence: 99%

Bovine Herpesvirus 1 UL49.5 Protein Inhibits the Transporter Associated with Antigen Processing despite Complex Formation with Glycoprotein M

Lipińska

Koppers-Lalić

Rychłowski

et al. 2006

J Virol

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“…Of the latter, those mediating viral entry, namely, gB, gD, and the gH/gL complex, are essential for the propagation of the virus (3). In contrast, the viral glycoprotein M (gM) is conserved throughout the family and typically critical for beta-and gammaherpesviruses but is not essential for most alphaherpesviruses, including HSV-1 (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16). Consequently, when gM is depleted from HSV-1 or the related alphaherpesvirus pseudorabies virus, viral yields are minimally reduced by 3-to 50-fold.…”

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Herpes Simplex Virus 1 gN Partners with gM To Modulate the Viral Fusion Machinery

Kasmi

Lippé

2015

J Virol

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Herpes simplex virus 1 (HSV-1) capsids are assembled in the nucleus, where they incorporate the viral genome. They then transit through the two nuclear membranes and are wrapped by a host-derived envelope. In the process, several HSV-1 proteins are targeted to the nuclear membranes, but their roles in viral nuclear egress are unclear. Among them, glycoprotein M (gM), a known modulator of virus-induced membrane fusion, is distributed on both the inner and outer nuclear membranes at the early stages of the infection, when no other viral glycoproteins are yet present there. Later on, it is found on perinuclear virions and ultimately redirected to the trans-Golgi network (TGN), where it cycles with the cell surface. In contrast, transfected gM is found only at the TGN and cell surface, hinting at an interaction with other viral proteins. Interestingly, many herpesvirus gM analogs interact with their gN counterparts, which typically alters their intracellular localization. To better understand how HSV-1 gM localization is regulated, we evaluated its ability to bind gN and discovered it does so in both transfected and infected cells, an interaction strongly weakened by the deletion of the gM amino terminus. Functionally, while gN had no impact on gM localization, gM redirected gN from the endoplasmic reticulum (ER) to the TGN. Most interestingly, gN overexpression stimulated the formation of syncytia in the context of an infection by a nonsyncytial strain, indicating that gM and gN not only physically but also functionally interact and that gN modulates gM's activity on membrane fusion. H erpesviridae are among the most complex human viruses from the point of view of their large genomes and viral particle composition. Among them, herpes simplex virus 1 (HSV-1), the prototype of human alphaherpesviruses, incorporates its 152-kb genome into an icosahedral capsid surrounded by a multiprotein tegument layer and a cell-derived lipid layer containing over a dozen viral proteins (1, 2). Of the latter, those mediating viral entry, namely, gB, gD, and the gH/gL complex, are essential for the propagation of the virus (3). In contrast, the viral glycoprotein M (gM) is conserved throughout the family and typically critical for beta-and gammaherpesviruses but is not essential for most alphaherpesviruses, including HSV-1 (4-16). Consequently, when gM is depleted from HSV-1 or the related alphaherpesvirus pseudorabies virus, viral yields are minimally reduced by 3-to 50-fold. However, its impact is substantially increased when U L 11 and gE/gI are codepleted in combination with gM, likely due to overlapping functions between these viral proteins (5,(17)(18)(19). IMPORTANCE HSV-1 gM is an important modulator of virally induced cell-cell fusion and viral entry, a process that is likely finely modulatedDespite its nonessential status in tissue culture, gM of several alphaherpesviruses has been associated with a number of functions throughout the viral life cycle (7,10,(19)(20)(21)(22). The glycoprotein is thus known to downregu...

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“…Moreover, PrV gM interacts via its cytoplasmic tail with the major tegument protein pUL49 (12). Interestingly, in the mammalian alphaherpesviruses HSV-1, PrV, and equine herpesvirus 1 (EHV-1) deletion of gM only slightly affected replication (6,10,35,49), whereas the gM homologs of Marek's disease virus, HCMV, Epstein-Barr virus (EBV), EHV-4, and murine gammaherpesvirus 68 are required for efficient virus replication in cell culture (17,29,36,58,61), indicating differing requirements within the Herpesviridae also for this protein.…”

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Effects of Simultaneous Deletion of pUL11 and Glycoprotein M on Virion Maturation of Herpes Simplex Virus Type 1

Leege

Fuchs

Granzow

et al. 2009

J Virol

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A glycoprotein M-deleted equid herpesvirus 4 is severely impaired in virus egress and cell-to-cell spread

Cited by 18 publications

References 32 publications

Bovine Herpesvirus 1 UL49.5 Protein Inhibits the Transporter Associated with Antigen Processing despite Complex Formation with Glycoprotein M

Bovine Herpesvirus 1 UL49.5 Protein Inhibits the Transporter Associated with Antigen Processing despite Complex Formation with Glycoprotein M

Herpes Simplex Virus 1 gN Partners with gM To Modulate the Viral Fusion Machinery

Effects of Simultaneous Deletion of pUL11 and Glycoprotein M on Virion Maturation of Herpes Simplex Virus Type 1

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