The role of proteolytic processing in the morphogenesis of virus particles

Hellen, Christopher U.T.; Wimmer, Eckard

doi:10.1007/bf01923512

Cited by 40 publications

(26 citation statements)

References 135 publications

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“…While proteolytic degradation events have rarely been described during virus entry (Greber et al, 1994), viral proteases are known to play a crucial role during the assembly of numerous viruses (see Hellen and Wimmer, 1992). For adenovirus, the role of a protease during virus assembly is illustrated by the tsl mutant which lacks L3/ p23 protease (Weber, 1976;Rancourt et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

The role of the adenovirus protease on virus entry into cells.

et al. 1996

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Adenovirus uncoating is a stepwise process which culminates in the release of the viral DNA into the nucleus through the nuclear pore complexes and dissociation of the capsid. Using quantitative biochemical, immunochemical and morphological methods, we demonstrate that inhibitors of the cystine protease, L3/p23, located inside the capsid block the degradation of the capsid-stabilizing protein VI, and prevent virus uncoating at the nuclear membrane. There was no effect on virus internalization, fiber shedding and virus binding to the nuclear envelope. The viral enzyme (dormant in the extracellular virus) was activated by two separate signals, neither of which was sufficient alone; virus interaction with the integrin receptor (inhibited with RGD peptides) and re-entry of the virus particle into a reducing environment in the endosome or the cytosol. Incorrectly assembled mutant viruses that lack the functional protease (ts1) failed at releasing fibers and penetrating into the cytosol. The results indicated that L3/p23 is needed not only to assemble an entry-competent virus but also to disassemble the incoming virus. The EMBO Journal vol.15 no.8 pp.1766-1777, 1996 The role of the adenovirus protease in virus entry into cells Adenovirus uncoating is a stepwise process which culminates in the release of the viral DNA into the nucleus through the nuclear pore complexes and dissociation of the capsid. Using quantitative biochemical, immunochemical and morphological methods, we demonstrate that inhibitors of the cysteine protease, L3/ p23, located inside the capsid block the degradation of the capsid-stabilizing protein VI, and prevent virus uncoating at the nuclear membrane. There was no effect on virus internalization, fiber shedding and virus binding to the nuclear envelope. The viral enzyme (dormant in the extracellular virus) was activated by two separate signals, neither of which was sufficient alone; virus interaction with the integrin receptor (inhibited with RGD peptides) and re-entry of the virus particle into a reducing environment in the endosome or the cytosol. Incorrectly assembled mutant viruses that lack the functional protease (tsl) failed at releasing fibers and penetrating into the cytosol. The results indicated that L3/p23 is needed not only to assemble an entry-competent virus but also to disassemble the incoming virus.

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Section: Discussionmentioning

confidence: 99%

The role of the adenovirus protease on virus entry into cells.

et al. 1996

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“…Alternative structures may be formed by proteins making up macromolecular particles with repeating subunits. Good examples are viral capsid proteins which can function as quasi-equivalent subunits by assuming alternative conformations in the symmetrical structure of the virion [48]. The capsid protein of cowpea chlorotic mottle virus has been shown to form icosahedra, sheets, and cylinders depending on the experimental conditions used [49] (reviewed in [34]).…”

Section: Discussionmentioning

confidence: 99%

In Vitro Assembly Properties of Purified Bacterially Expressed Capsid Proteins of Human Immunodeficiency Virus

Gross

Hohenberg

Kräusslich

1997

European Journal of Biochemistry

189

229

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The Gag polyprotein of retroviruses is sufficient for embly antl budding of virus-like particles from the host cell. In the case of human immunodeficiency virus (HTV), Gag contains the domains matrix, capsid (CA), nucleocapsid (NC) and p6 which are separated by the viral proteinase inside the nascent virion, leading to morphological maturation to yield an infectious virus. In the mature virus, CA forms a capsid shell surrounding the ribonucleoprotein core consisting of NC and the genomic RNA. To define requirements for particle assembly and functional contributions of individual domains, we expressed domains of HIV Gag in Escherichiu coli and purified the products to near homogeneity. In vitro assembly of CA, with or without the C-terminally adjacent spacer peptide, yielded tubular structures with a diameter of approximately 55 nm and heterogeneous length. Efficient particle formation required high protein Concentration, high salt and neutral to alkaline pH. In contrast, in iitro assembly of CA-NC occurred at a 20-fold lower protein concentration and in low salt, but required addition of RNA. These results suggest that hydrophobic interactions of capsid proteins are sufficient for particle formation while the RNAbinding iiucleocapsid domain may concentrate and align structural protcins on the viral genome.

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“…Viruses have adopted similar strategies. For example in the retroviruses, it has been proposed that the acidic extracellular environment triggers the morphogenic cleavage of structural proteins by displacing a portion of the gag-pol polyprotein which prevents the active site of the proteinase from interacting with its substrate while within the cell [11]. In the case of adenoviruses, it appears that a disulphide-linked peptide produced from the pVI structural protein during the latter stages of replication is required for the activation of the viral proteinase and subsequent virus maturation [21].…”

Section: General Overview Of Viral Proteolysismentioning

confidence: 99%

“…Proteolytic cleavage of viral polypeptides have been categorised as 'formative' or 'morphogenic' proteolysis, depending on the function the reaction serves during the replicative cycle [11].…”

Section: General Overview Of Viral Proteolysismentioning

confidence: 99%

Vaccinia virus proteolysis—a review

Byrd

Hruby

2006

Reviews in Medical Virology

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It is well known that viruses, as obligate intracellular parasites, must use their hosts' metabolic machinery in order to replicate their genomes and form infectious progeny virions. What is less well known are the details of how viruses make sure that once all the necessary proteins are made, that they assume the correct configuration at the proper time in order to catalyse the efficient assembly of infectious virions. One of the methods employed by viruses to regulate this process is the proteolytic cleavage of viral proteins. Over the past several decades, studies in numerous laboratories have demonstrated that morphogenic proteolysis plays a major and essential role during the assembly and maturation of infectious poxvirus virions. In this review we describe the history of vaccinia virus proteolysis as a prototypic viral system.

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The role of proteolytic processing in the morphogenesis of virus particles

Cited by 40 publications

References 135 publications

The role of the adenovirus protease on virus entry into cells.

The role of the adenovirus protease on virus entry into cells.

In Vitro Assembly Properties of Purified Bacterially Expressed Capsid Proteins of Human Immunodeficiency Virus

Vaccinia virus proteolysis—a review

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