Herpes Simplex Virus Type 2 Glycoprotein Biogenesis: Effect of Monensin on Glycoprotein Maturation, Intracellular Transport and Virus Infectivity

Ghosh‐Choudhury, Nandini; Graham, Alex; Ghosh, Hara P.

doi:10.1099/0022-1317-68-7-1939

Cited by 14 publications

(12 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Acyclovir is phosphorylated by HSV thymidine kinase, resulting in formation of an active inhibitor of viral DNA replication (11). Interestingly, monensin and brefeldin A, which have been reported to inhibit HSV replication (9,10,21,26), dramatically changed the localization patterns and expression levels of viral proteins in cells infected with YK608 (data not shown). The imaging system described here, modified for rapid data acquisition and high throughput, combined with HSV-1 YK608 could be the basis for development of new screening systems for anti-HSV agents that target virion maturation pathways.…”

Section: Discussionmentioning

confidence: 93%

Simultaneous Tracking of Capsid, Tegument, and Envelope Protein Localization in Living Cells Infected with Triply Fluorescent Herpes Simplex Virus 1

Sugimoto

Uema²,

Sagara

et al. 2008

J Virol

135

180

View full text Add to dashboard Cite

We report here the construction of a triply fluorescent-tagged herpes simplex virus 1 (HSV-1) expressing capsid protein VP26, tegument protein VP22, and envelope protein gB as fusion proteins with monomeric yellow, red, and cyan fluorescent proteins, respectively. The recombinant virus enabled us to monitor the dynamics of these capsid, tegument, and envelope proteins simultaneously in the same live HSV-1-infected cells and to visualize single extracellular virions with three different fluorescent emissions. In Vero cells infected by the triply fluorescent virus, multiple cytoplasmic compartments were found to be induced close to the basal surfaces of the infected cells (the adhesion surfaces of the infected cells on the solid growth substrate). Major capsid, tegument, and envelope proteins accumulated and colocalized in the compartments, as did marker proteins for the trans-Golgi network (TGN) which has been implicated to be the site of HSV-1 secondary envelopment. Moreover, formation of the compartments was correlated with the dynamic redistribution of the TGN proteins induced by HSV-1 infection. These results suggest that HSV-1 infection causes redistribution of TGN membranes to form multiple cytoplasmic compartments, possibly for optimal secondary envelopment. This is the first real evidence for the assembly of all three types of herpesvirus proteins-capsid, tegument, and envelope membrane proteins-in TGN.Herpes simplex virus 1 (HSV-1) consists of three morphologically distinct structures: nucleocapsid, tegument, and envelope (58). The nucleocapsid contains the linear doublestranded DNA viral genome in an icosahedral capsid (58). The nucleocapsid is surrounded by a proteinaceous layer designated the tegument, which is enclosed by an envelope that is a host cell-derived lipid bilayer containing virus-encoded glycoproteins (58). After virus entry into the host cell, the deenveloped nucleocapsids reach the nucleopores, and the viral genome enters the nucleus (58). Subsequently, viral DNA replication and packaging of nascent progeny virus genomes into assembling capsids take place within nuclear compartments, called replication compartments (12,56,58). The progeny nucleocapsids then acquire primary envelopes by budding through the inner nuclear membrane into the space between the inner and the outer nuclear envelopes, called the perinuclear space (39, 58). While assembly of progeny nucleocapsids within the nucleus and primary envelopment of nucleocapsids at the inner nuclear membrane have been well documented, the route of the nascent virions from the perinuclear space to the extracellular space is controversial (7,34,41,42,58,66). It is now generally accepted that perinuclear virions lose their envelopes by fusion with the outer nuclear membrane, thereby releasing naked nucleocapsids in the cytoplasm (40,41,60). These nucleocapsids must acquire tegument proteins in the cytoplasm and/or upon budding through the nuclear membrane and must be enveloped again at cytoplasmic membranes (secondary envelopment), probabl...

show abstract

Section: Discussionmentioning

confidence: 93%

Simultaneous Tracking of Capsid, Tegument, and Envelope Protein Localization in Living Cells Infected with Triply Fluorescent Herpes Simplex Virus 1

Sugimoto

Uema²,

Sagara

et al. 2008

J Virol

135

180

View full text Add to dashboard Cite

show abstract

“…An impairment in N-linked oligosaccharide processing of HSV glycoproteins results in defective egress of progeny virus (Johnson & Spear, 1983;Serafini-Cessi et al, 1983;Dall'Olio et al, 1986;Ghosh-Choudhury et al, 1987), in inhibition of virus-induced cell fusion (Campadelli-Fiume et al, 1982) and in abolition of the infectivity of HSV (Pizer et al, 1980;Svennerholm et al, 1982; see also . Whether an impairment in O-linked oligosaccharide assembly affects any function of HSV glycoproteins and, if it does, whether it affects the same or different functions as the impairment in N-linked chain assembly, is not known.…”

Section: Discussionmentioning

confidence: 99%

Comparative Study on O-linked Oligosaccharides of Glycoprotein D of Herpes Simplex Virus Types 1 and 2

Serafini‐Cessi¹,

Dall’Olio²,

Malagolini³

et al. 1988

Journal of General Virology

View full text Add to dashboard Cite

SUMMARYGlycoproteins D1 (gD1) and D2 (gD2) of herpes simplex virus type 1 and type 2, respectively, were purified from infected HEp-2 cells labelled with [3H]glucosamine for 14 h followed by a 3 h chase using HD1 monoclonal antibody linked to Sepharose. Olinked oligosaccharides were found to be present in both glycoproteins. The identification of N-acetyl [3H]galactosaminitol as the major labelled component in the oligosaccharides generated by mild alkaline borohydride treatment demonstrated that these chains have N-acetylgalactosamine at the reducing end. These oligosaccharides consist of mono-and disialylated species with a predominance of the latter species in gD1. Size analysis and radioactive amino sugar composition strongly suggest a structure in which the galactosyl-N-acetylgalactosamine core is substituted with one or two sialic acid residues. In terms of [3H]glucosamine-derived radioactivity, O-linked oligosaccharides are less represented than N-linked oligosaccharides. The O-linked oligosaccharide number determination showed that gD1 and gD2 carry two and three chains, respectively.

show abstract

“…Monensin is used extensively in the beef and dairy industries to prevent coccidiosis, enhance growth, or prevent bloat (33)(34)(35)(36). Monensin also has antiviral effects on different viruses, such as human immunodeficiency virus (HIV) (37,38), simian virus 40 (SV40) (39), and herpes simplex virus (HSV) (40).…”

mentioning

confidence: 99%

New Insights into the Understanding of Hepatitis C Virus Entry and Cell-to-Cell Transmission by Using the Ionophore Monensin A

Fénéant

Potel

François³

et al. 2015

J Virol

View full text Add to dashboard Cite

In our study, we characterized the effect of monensin, an ionophore that is known to raise the intracellular pH, on the hepatitis C virus (HCV) life cycle. We showed that monensin inhibits HCV entry in a pangenotypic and dose-dependent manner. Monensin induces an alkalization of intracellular organelles, leading to an inhibition of the fusion step between viral and cellular membranes. Interestingly, we demonstrated that HCV cell-to-cell transmission is dependent on the vesicular pH. Using the selective pressure of monensin, we selected a monensin-resistant virus which has evolved to use a new entry route that is partially pH and clathrin independent. Characterization of this mutant led to the identification of two mutations in envelope proteins, the Y297H mutation in E1 and the I399T mutation in hypervariable region 1 (HVR1) of E2, which confer resistance to monensin and thus allow HCV to use a pH-independent entry route. Interestingly, the I399T mutation introduces an N-glycosylation site within HVR1 and increases the density of virions and their sensitivity to neutralization with anti-apolipoprotein E (anti-ApoE) antibodies, suggesting that this mutation likely induces conformational changes in HVR1 that in turn modulate the association with ApoE. Strikingly, the I399T mutation dramatically reduces HCV cell-to-cell spread. In summary, we identified a mutation in HVR1 that overcomes the vesicular pH dependence, modifies the biophysical properties of particles, and drastically reduces cellto-cell transmission, indicating that the regulation by HVR1 of particle association with ApoE might control the pH dependence of cell-free and cell-to-cell transmission. Thus, HVR1 and ApoE are critical regulators of HCV propagation. IMPORTANCEAlthough several cell surface proteins have been identified as entry factors for hepatitis C virus (HCV), the precise mechanisms regulating its transmission to hepatic cells are still unclear. In our study, we used monensin A, an ionophore that is known to raise the intracellular pH, and demonstrated that cell-free and cell-to-cell transmission pathways are both pH-dependent processes. We generated monensin-resistant viruses that displayed different entry routes and biophysical properties. Thanks to these mutants, we highlighted the importance of hypervariable region 1 (HVR1) of the E2 envelope protein for the association of particles with apolipoprotein E, which in turn might control the pH dependency of cell-free and cell-to-cell transmission. H epatitis C virus (HCV) infection is a global public health problem affecting over 130 million individuals worldwide.Chronic HCV infection can result in liver cirrhosis and hepatocellular carcinoma (1). While previous interferon (IFN)-based therapies have been limited by drug resistance and marked toxicity (2), the recently clinically licensed direct-acting antivirals are expected to cure the large majority of infected patients without major adverse effects (3). Nevertheless, several challenges remain: high costs limit access to therapy ...

show abstract

Herpes Simplex Virus Type 2 Glycoprotein Biogenesis: Effect of Monensin on Glycoprotein Maturation, Intracellular Transport and Virus Infectivity

Cited by 14 publications

References 24 publications

Simultaneous Tracking of Capsid, Tegument, and Envelope Protein Localization in Living Cells Infected with Triply Fluorescent Herpes Simplex Virus 1

Simultaneous Tracking of Capsid, Tegument, and Envelope Protein Localization in Living Cells Infected with Triply Fluorescent Herpes Simplex Virus 1

Comparative Study on O-linked Oligosaccharides of Glycoprotein D of Herpes Simplex Virus Types 1 and 2

New Insights into the Understanding of Hepatitis C Virus Entry and Cell-to-Cell Transmission by Using the Ionophore Monensin A

Contact Info

Product

Resources

About