Basolateral Budding of Marburg Virus: VP40 Retargets Viral Glycoprotein GP to the Basolateral Surface

Kolesnikova, Larissa; Ryabchikova, E. I.; Shestopalov, А. М.; Becker, Stephan

doi:10.1086/520584

Cited by 50 publications

(49 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Late in infection, ongoing cell-to-cell fusion and virus replication cause extensive cytopathic effects and likely disrupt all basolateral trafficking pathways. The consecutive accumulation of the glycoproteins at apical surfaces might be triggered by an apical G/F retargeting promoted by the M protein, as proposed previously for other viruses (25,29,30,34,68,69). However, there is no evidence so far that G, F, and M meet and interact intracellularly before reaching the plasma membrane.…”

Section: Discussionmentioning

confidence: 60%

“…Envelope proteins can even be expressed at opposing membranes. Here, partial retargeting of the glycoproteins by the matrix protein to the site of budding is believed to be required for virus release (25,29,30,34,68,69). Resembling measles virus (29), NiV M, F, and G proteins possess opposing targeting signals.…”

Section: Discussionmentioning

confidence: 99%

“…While virus entry is de- termined mainly by the distribution of viral receptors, virus release is directed by the localization of the viral surface glycoproteins or the matrix protein (29,31,34,(47)(48)(49)(50). To analyze budding polarity in epithelial cells, polarized MDCK cells were infected with high and low doses of NiV, and virus titers in the cell culture media from the apical and basal filter chambers were determined.…”

Section: Ephrin Receptor Expression and Niv Entry Are Bipolarmentioning

confidence: 99%

See 2 more Smart Citations

Nipah Virus Entry and Egress from Polarized Epithelial Cells

Lamp

Dietzel

Kolesnikova

et al. 2013

J Virol

Self Cite

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 60%

Section: Discussionmentioning

confidence: 99%

Section: Ephrin Receptor Expression and Niv Entry Are Bipolarmentioning

confidence: 99%

See 1 more Smart Citation

Nipah Virus Entry and Egress from Polarized Epithelial Cells

Lamp

Dietzel

Kolesnikova

et al. 2013

J Virol

Self Cite

View full text Add to dashboard Cite

“…In contrast, analyses using influenza virus, VSV, and human respiratory syncytial virus showed that while their glycoproteins are located at the site of virus budding, they are not the direction-determining factors (6,50,74). For Marburg virus and measles virus, the matrix protein was described to be the determining factor for directional virus release (33,51).…”

Section: Discussionmentioning

confidence: 97%

Viral Protein Determinants of Lassa Virus Entry and Release from Polarized Epithelial Cells

Schlie

Maisa

Freiberg

et al. 2010

J Virol

View full text Add to dashboard Cite

The epithelium plays a key role in the spread of Lassa virus. Transmission from rodents to humans occurs mainly via inhalation or ingestion of droplets, dust, or food contaminated with rodent urine. Here, we investigated Lassa virus infection in cultured epithelial cells and subsequent release of progeny viruses. We show that Lassa virus enters polarized Madin-Darby canine kidney (MDCK) cells mainly via the basolateral route, consistent with the basolateral localization of the cellular Lassa virus receptor ␣-dystroglycan. In contrast, progeny virus was efficiently released from the apical cell surface. Further, we determined the roles of the glycoprotein, matrix protein, and nucleoprotein in directed release of nascent virus. To do this, a virus-like-particle assay was developed in polarized MDCK cells based on the finding that, when expressed individually, both the glycoprotein GP and matrix protein Z form virus-like particles. We show that GP determines the apical release of Lassa virus from epithelial cells, presumably by recruiting the matrix protein Z to the site of virus assembly, which is in turn essential for nucleocapsid incorporation into virions.

show abstract

“…The accumulation of VP40 was observed upon its ectopic expression in filamentous plasma membrane protrusions; the fission of these protrusions results in the release of filamentous virus-like particles (VLPs) into the supernatant (12,13). The coexpression of VP40 with NP or with the viral surface protein GP induces the redistribution of NP and GP to the VP40-enriched plasma membrane protrusions and their subsequent incorporation into released VLPs (14)(15)(16)(17). Based on these observations, it is currently thought that VP40 functions as the main driver of MARV particle assembly and release.…”

Section: Importancementioning

confidence: 99%

A Single Amino Acid Change in the Marburg Virus Matrix Protein VP40 Provides a Replicative Advantage in a Species-Specific Manner

Koehler

Kolesnikova

Welzel

et al. 2016

J Virol

Self Cite

View full text Add to dashboard Cite

Marburg virus (MARV) induces severe hemorrhagic fever in humans and nonhuman primates but only transient nonlethal disease in rodents. However, sequential passages of MARV in rodents boosts infection leading to lethal disease. Guinea pig-adapted MARV contains one mutation in the viral matrix protein VP40 at position 184 (VP40 D184N ). The contribution of the D184N mutation to the efficacy of replication in a new host is unknown. In the present study, we demonstrated that recombinant MARV containing the D184N mutation in VP40 [rMARV VP40(D184N) ] grew to higher titers than wild-type recombinant MARV (rMARV WT ) in guinea pig cells. Moreover, rMARV VP40(D184N) displayed higher infectivity in guinea pig cells. Comparative analysis of VP40 functions indicated that neither the interferon (IFN)-antagonistic function nor the membrane binding capabilities of VP40 were affected by the D184N mutation. However, the production of VP40-induced virus-like particles (VLPs) and the recruitment of other viral proteins to the budding site was improved by the D184N mutation in guinea pig cells, which resulted in the higher infectivity of VP40 D184N -induced infectious VLPs (iVLPs) compared to that of VP40-induced iVLPs. In addition, the function of VP40 in suppressing viral RNA synthesis was influenced by the D184N mutation specifically in guinea pig cells, thus allowing greater rates of transcription and replication. Our results showed that the improved viral fitness of rMARV VP40(D184N) in guinea pig cells was due to the better viral assembly function of VP40 D184N and its lower inhibitory effect on viral transcription and replication rather than modulation of the VP40-mediated suppression of IFN signaling. IMPORTANCEThe increased virulence achieved by virus passaging in a new host was accompanied by mutations in the viral genome. Analyzing how these mutations affect the functions of viral proteins and the ability of the virus to grow within new host cells helps in the understanding of the molecular mechanisms increasing virulence. Using a reverse genetics approach, we demonstrated that a single mutation in MARV VP40 detected in a guinea pig-adapted MARV provided a replicative advantage of rMARV VP40(D184N) in guinea pig cells. Our studies show that this replicative advantage of rMARV VP40 D184N was based on the improved functions of VP40 in iVLP assembly and in the regulation of transcription and replication rather than on the ability of VP40 to combat the host innate immunity. F iloviruses, including Ebolaviruses (EBOV) and Marburg virus (MARV), are enveloped, nonsegmented, negative-strand RNA viruses (1). These viruses are known to cause severe fevers in humans and nonhuman primates, with case fatality rates of up to 90% (2). Although several antivirals and vaccines currently are being tested in clinical studies, none of them are licensed for human use. Therefore, work with filoviruses is restricted to biosafety level 4 (BSL-4) facilities. The recent EBOV outbreak in Guinea, Sierra Leone, and Liberia demonstrated the ...

show abstract

Basolateral Budding of Marburg Virus: VP40 Retargets Viral Glycoprotein GP to the Basolateral Surface

Cited by 50 publications

References 13 publications

Nipah Virus Entry and Egress from Polarized Epithelial Cells

Nipah Virus Entry and Egress from Polarized Epithelial Cells

Viral Protein Determinants of Lassa Virus Entry and Release from Polarized Epithelial Cells

A Single Amino Acid Change in the Marburg Virus Matrix Protein VP40 Provides a Replicative Advantage in a Species-Specific Manner

Contact Info

Product

Resources

About