Interactions among the three adenovirus core proteins

Chatterjee, Pranam; Vayda, Michael E.; Flint, S. J.

doi:10.1128/jvi.55.2.379-386.1985

Cited by 82 publications

(50 citation statements)

References 34 publications

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“…This is a 79aa protein precursor that is cleaved after virion assembly into three components, the middle 19aa of which comprise the mature protein X that is associated with viral DNA inside the particle alongside viral histone-like proteins pV and pVII (refs. [39][40][41] ). However, the roles of the other portions of preX that are liberated by this cleavage and any additional roles of the precursor relative to the mature protein are not understood.…”

Section: Discussionmentioning

confidence: 99%

Deep splicing plasticity of the human adenovirus type 5 transcriptome drives virus evolution

et al. 2020

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Viral genomes have high gene densities and complex transcription strategies rendering transcriptome analysis through short-read RNA-seq approaches problematic. Adenovirus transcription and splicing is especially complex. We used long-read direct RNA sequencing to study adenovirus transcription and splicing during infection. This revealed a previously unappreciated complexity of alternative splicing and potential for secondary initiating codon usage. Moreover, we find that most viral transcripts tend to shorten polyadenylation lengths as infection progresses. Development of an open reading frame centric bioinformatics analysis pipeline provided a deeper quantitative and qualitative understanding of adenovirus's genetic potential. Across the viral genome adenovirus makes multiple distinctly spliced transcripts that code for the same protein. Over 11,000 different splicing patterns were recorded across the viral genome, most occurring at low levels. This low-level use of alternative splicing patterns potentially enables the virus to maximise its coding potential over evolutionary timescales.

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Section: Discussionmentioning

confidence: 99%

Deep splicing plasticity of the human adenovirus type 5 transcriptome drives virus evolution

et al. 2020

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“…6d). Dimers of protein VI were also detected by crosslinking assays on disrupted virions and extracted cores (42) It has previously been shown that immature pVI has lytic activity, but binding to hexon shields this activity (36). The mature form of VI binds to the hexon cavity more weakly than the intermediate one (iVI), as indicated by assays where heating of Ad5 particles carrying the pVI G33A mutation caused release of mature protein VI, but not of iVI (36).…”

Section: Observation Of Partially Processed Protein VI In the Ad5-viimentioning

confidence: 94%

Dynamic competition for hexon binding between core protein VII and lytic protein VI promotes adenovirus maturation and entry

Hernando-Pérez

Martín-González

Pérez-Illana

et al. 2019

Preprint

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Adenovirus minor coat protein VI contains a membrane-disrupting peptide which is inactive when VI is bound to hexon trimers. Protein VI must be released during entry to ensure endosome escape. Hexon:VI stoichiometry has been uncertain, and only fragments of VI have been identified in the virion structure. Recent findings suggest an unexpected relationship between VI and the major core protein, VII. According to the high resolution structure of the mature virion, VI and VII may compete for the same binding site in hexon; and non-infectious human adenovirus type 5 particles assembled in the absence of VII (Ad5-VII-) are deficient in proteolytic maturation of protein VI and endosome escape. Here we show that Ad5-VII- particles are trapped in the endosome because they fail to increase VI exposure during entry. This failure was not due to increased particle stability, because capsid disruption happened at lower thermal or mechanical stress in Ad5-VII- compared to wildtype (Ad5-wt) particles. Cryo-EM difference maps indicated that VII can occupy the same binding pocket as VI in all hexon monomers, strongly arguing for binding competition. In the Ad5-VII- map, density corresponding to the immature amino-terminal region of VI indicates that in the absence of VII the lytic peptide is trapped inside the hexon cavity, and clarifies the hexon:VI stoichiometry conundrum. We propose a model where dynamic competition between proteins VI and VII for hexon binding facilitates the complete maturation of VI, and is responsible for releasing the lytic protein from the hexon cavity during entry and stepwise uncoating.Significance StatementCorrect assembly of an adenovirus infectious particle involves the highly regulated interaction of more than ten different proteins as well as the viral genome. Here we examine the interplay between two of these proteins: the major core protein VII, involved in genome condensation, and the multifunctional minor coat protein VI. Protein VI binds to the inner surface of adenovirus hexons (trimers of the major coat protein) and contains a lytic peptide which must be released during entry to ensure endosome rupture. We present data supporting a dynamic competition model between proteins VI and VII for hexon binding during assembly. This competition facilitates the release of the lytic peptide from the hexon cavity and ensures virus escape from the early endosome.

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“…per OD 260 unit. Ad2 virions labelled with [35S]methionine were prepared as described previously (Chatterjee et al, 1985). Virions labelled with [3H]thymidine were purified from HeLa cells infected with 40 p.f.u.…”

Section: Methodsmentioning

confidence: 99%

Adenoviral protein VII packages intracellular viral DNA throughout the early phase of infection.

Chatterjee¹,

Vayda²,

Flint³

1986

The EMBO Journal

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The proteins associated with parental, adenoviral DNA in productively‐infected HeLa cells have been examined both directly and indirectly. HeLa cells infected with 32P‐labelled Ad2 were irradiated with u.v. light at various points in the infectious cycle. Following degradation of the DNA, nuclear proteins carrying cross‐linked nucleotides, or oligonucleotides, were distinguished from virion phosphoproteins by the resistance of their 32P radioactivity to 1 M NaOH. The major core protein of the virion, protein VII, was found to be associated with viral DNA throughout infection, even when cells were infected at a multiplicity of 0.14. Micrococcal nuclease digestion of intranuclear viral DNA 4 h after infection liberated two nucleoprotein particles containing viral DNA, neither of which co‐migrated with HeLa cell mononucleosomes. These results indicate that core protein VII remains associated with parental adenoviral DNA during productive infections. The observation that protein VII can be cross‐linked to DNA in cells infected at very low multiplicity, together with the results of a comparison of proteins cross‐linkable to viral DNA in cells infected by wild‐type virus and a non‐infectious mutant containing the precursor to protein VII, suggest that nucleoproteins comprising viral DNA and protein VII must be the templates for expression of pre‐early and early viral genes.

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Interactions among the three adenovirus core proteins

Cited by 82 publications

References 34 publications

Deep splicing plasticity of the human adenovirus type 5 transcriptome drives virus evolution

Deep splicing plasticity of the human adenovirus type 5 transcriptome drives virus evolution

Dynamic competition for hexon binding between core protein VII and lytic protein VI promotes adenovirus maturation and entry

Adenoviral protein VII packages intracellular viral DNA throughout the early phase of infection.

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