The unique role of domain 2A of the hepatitis A virus precursor polypeptide P1-2A in viral morphogenesis

Morace, G; Kusov, Yuri; Dzagurov, Georgy; Beneduce, Francesca; Gauss‐Müller, Verena

doi:10.5483/bmbrep.2008.41.9.678

Cited by 17 publications

(12 citation statements)

References 13 publications

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“…However, in other genera, e.g., cardioviruses, aphthoviruses, and hepatoviruses, a primary cleavage event occurs at the C terminus of 2A so that the capsid precursor protein comprises P1-2A (46). The role of 2A, if any, in the subsequent processing and assembly of the structural proteins of cardio-and aphthoviruses is unclear, but for hepatoviruses, it plays an important role in the assembly process, although it is cleaved away from VP1 in the mature virion (15,42,51). Finally, the cleavage of VP0 into VP2 and VP4 occurs at the final stage of virus particle maturation and has important effects on particle stability, priming the particle in a metastable state in preparation for conformational changes involved in the cell entry process required to establish a new infection (17).…”

Section: Discussionmentioning

confidence: 99%

“…However, in some other picornavirus genera, including the aphthoviruses, the capsid precursor has an additional Cterminal extension and is known as P1-2A (46). In hepatitis A virus, the 2A component is involved in the particle assembly mechanism, although it is absent from the mature virion (15,42,51). However, the role of 2A in the assembly of FMDV is unclear.…”

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confidence: 99%

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Foot-and-Mouth Disease Virus Assembly: Processing of Recombinant Capsid Precursor by Exogenous Protease Induces Self-Assembly of Pentamers In Vitro in a Myristoylation-Dependent Manner

Goodwin

Tuthill

Arias

et al. 2009

J Virol

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The assembly of foot-and-mouth disease virus (FMDV) particles is poorly understood. In addition, there are important differences in the antigenic and receptor binding properties of virus assembly and dissociation intermediates, and these also remain unexplained. We have established an experimental model in which the antigenicity, receptor binding characteristics, and in vitro assembly of capsid precursor can be studied entirely from purified components. Recombinant capsid precursor protein (P1 region) was expressed in Escherichia coli as myristoylated or unmyristoylated protein. The protein sedimented in sucrose gradients at 5S and reacted with monoclonal antibodies which recognize conformational or linear antigen determinants on the virion surface. In addition, it bound the integrin ␣ v ␤ 6 , a cellular receptor for FMDV, indicating that unprocessed recombinant capsid precursor is both structurally and antigenically similar to native virus capsid. These characteristics were not dependent on the presence of 2A at the C terminus but were altered by N-terminal myristoylation and in mutant precursors which lacked VP4. Proteolytic processing of myristoylated precursor by recombinant FMDV 3C pro in vitro induced a shift in sedimentation from 5S to 12S, indicating assembly into pentameric capsid subunits. Nonmyristoylated precursor still assembled into higher-order structures after processing with 3Cpro , but these particles sedimented in sucrose gradients at approximately 17S. In contrast, mutant precursors lacking VP4 were antigenically distinct, were unable to form pentamers, and had reduced capacity for binding integrin receptor. These studies demonstrate the utility of recombinant capsid precursor protein for investigating the initial stages of assembly of FMDV and other picornaviruses.Foot-and-mouth disease virus (FMDV) is the etiological agent of a highly infectious disease of cattle and other clovenhoofed animals. It is of economic importance, because the presence of the disease results in severe restrictions of international trade. In many parts of the developing world, the disease is endemic, and it continues to pose a serious threat to livestock industries globally, as exemplified by recent major outbreaks in the United Kingdom, Argentina, and Uruguay.FMDV is a small, nonenveloped, positive-strand RNA virus belonging to the genus Aphthovirus within the family Picornaviridae. Other members of the family include poliovirus (PV; genus Enterovirus) and hepatitis A virus (genus Hepatovirus). The mature picornavirus comprises 60 copies each of four structural proteins, termed VP1, VP2, VP3, and VP4, which encapsidate a single, positive-sense RNA genome. The proteins form a pseudo Tϭ3 icosahedral capsid with VP1 located close to the fivefold axes of symmetry and VP2 and VP3 alternating around the threefold axes (24). VP4, which is myristoylated at the N terminus, is an internal component of the capsid (13,48).Although the morphogenesis of picornaviral particles is not completely understood, it is known that capsid...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Foot-and-Mouth Disease Virus Assembly: Processing of Recombinant Capsid Precursor by Exogenous Protease Induces Self-Assembly of Pentamers In Vitro in a Myristoylation-Dependent Manner

Goodwin

Tuthill

Arias

et al. 2009

J Virol

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“…Subsequently, cleavage occurs at the VP1/2A junction to release the mature 2A protein (Cohen et al, 2002). This cleavage is carried out by cellular proteinases such as Factor Xa, trypsin, and cathepsin L ( Figure 6 ) and it requires Arg 278 to be present at the VP1/2A junction (Rachow et al, 2003; Morace et al, 2008). Targeting this 2A protein may interfere the formation of the icosahedral viral capsid.…”

Section: Unique 2a Protein In Hepatitis a Virus (Hav)mentioning

confidence: 99%

Structures and Corresponding Functions of Five Types of Picornaviral 2A Proteins

et al. 2017

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Among the few non-structural proteins encoded by the picornaviral genome, the 2A protein is particularly special, irrespective of structure or function. During the evolution of the Picornaviridae family, the 2A protein has been highly non-conserved. We believe that the 2A protein in this family can be classified into at least five distinct types according to previous studies. These five types are (A) chymotrypsin-like 2A, (B) Parechovirus-like 2A, (C) hepatitis-A-virus-like 2A, (D) Aphthovirus-like 2A, and (E) 2A sequence of the genus Cardiovirus. We carried out a phylogenetic analysis and found that there was almost no homology between each type. Subsequently, we aligned the sequences within each type and found that the functional motifs in each type are highly conserved. These different motifs perform different functions. Therefore, in this review, we introduce the structures and functions of these five types of 2As separately. Based on the structures and functions, we provide suggestions to combat picornaviruses. The complexity and diversity of the 2A protein has caused great difficulties in functional and antiviral research. In this review, researchers can find useful information on the 2A protein and thus conduct improved antiviral research.

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“…The primary cotranslational cleavage of the viral polyprotein takes place between 2A and 2B and is accomplished by the viral proteinase 3C pro (or its precursor), leaving the 2A sequence fused to the carboxyl terminus of capsid protein VP1 (REFS 116,117). In immature virions, VP1 retains this 2A extension, which is eventually cleaved off by an unidentified enzyme 118 . The involvement of 2A in the maturation of some other picornaviruses cannot be excluded therefore.…”

Section: Division Of Labour In Picornavirus Proteinsmentioning

confidence: 99%

Viral security proteins: counteracting host defences

Agol

Gmyl

2010

Nat Rev Microbiol

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Interactions with host defences are key aspects of viral infection. Various viral proteins perform counter-defensive functions, but a distinct class, called security proteins, is dedicated specifically to counteracting host defences. Here, the properties of the picornavirus security proteins L and 2A are discussed. These proteins have well-defined positions in the viral polyprotein, flanking the capsid precursor, but they are structurally and biochemically unrelated. Here, we consider the impact of these two proteins, as well as that of a third security protein, L(*), on viral reproduction, pathogenicity and evolution. The concept of security proteins could serve as a paradigm for the dedicated counter-defensive proteins of other viruses.

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The unique role of domain 2A of the hepatitis A virus precursor polypeptide P1-2A in viral morphogenesis

Cited by 17 publications

References 13 publications

Foot-and-Mouth Disease Virus Assembly: Processing of Recombinant Capsid Precursor by Exogenous Protease Induces Self-Assembly of Pentamers In Vitro in a Myristoylation-Dependent Manner

Foot-and-Mouth Disease Virus Assembly: Processing of Recombinant Capsid Precursor by Exogenous Protease Induces Self-Assembly of Pentamers In Vitro in a Myristoylation-Dependent Manner

Structures and Corresponding Functions of Five Types of Picornaviral 2A Proteins

Viral security proteins: counteracting host defences

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