Peptide mapping of human adenovirus type 6 and simian adenovirus type 7 hexon and core protein

ABSTRACT The early region 1A (E1A) gene is the first gene expressed after infection with adenovirus and has been most extensively characterized in human adenovirus type 5 (hAd5). The E1A proteins interact with numerous cellular regulatory proteins, influencing a variety of transcriptional and cell cycle events. For this reason, these multifunctional proteins have been useful as tools for dissecting pathways regulating cell growth and gene expression. Despite the large number of studies using hAd5 E1A, relatively little is known about the function of the E1A proteins of other adenoviruses. In 1985, a comparison of E1A sequences from three human and one simian adenovirus identified three regions with higher overall levels of sequence conservation designated conserved regions (CR) 1, 2, and 3. As expected, these regions are critical for a variety of E1A functions. Since that time, the sequences of several other human and simian adenovirus E1A proteins have been determined. Using these, and two additional sequences that we determined, we report here a detailed comparison of the sequences of 15 E1A proteins representing each of the six hAd subgroups and several simian adenoviruses. These analyses refine the positioning of CR1, 2, and 3; define a fourth CR located near the carboxyl terminus of E1A; and suggest several new functions for E1A.

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A NEW SIMIAN ADENOVIRUS SEROLOGICALLY RELATED TO HUMAN ADENOVIRUS TYPE 2 FROM A CHIMPANZEE WITH “VIRAL HEPATITIS”12

American Journal of Epidemiology ◽

10.1093/oxfordjournals.aje.a121079 ◽

1969 ◽

Vol 90 (4) ◽

pp. 344-353 ◽

Cited By ~ 6

Author(s):

WILLIAM D. HILLIS ◽

ANNA C. GARNER ◽

ARGYE I. HILLIS

Keyword(s):

Viral Hepatitis ◽

Human Adenovirus ◽

Adenovirus Type ◽

Simian Adenovirus ◽

Adenovirus Type 2

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Thermostability/Infectivity Defect Caused by Deletion of the Core Protein V Gene in Human Adenovirus Type 5 Is Rescued by Thermo-selectable Mutations in the Core Protein X Precursor

Journal of Molecular Biology ◽

10.1016/j.jmb.2006.11.090 ◽

2007 ◽

Vol 366 (4) ◽

pp. 1142-1160 ◽

Cited By ~ 24

Author(s):

Hideyo Ugai ◽

Anton V. Borovjagin ◽

Long P. Le ◽

Minghui Wang ◽

David T. Curiel

Keyword(s):

Core Protein ◽

Human Adenovirus ◽

Adenovirus Type ◽

The Core ◽

Protein X ◽

V Gene ◽

Adenovirus Type 5

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

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1920896117 ◽

2020 ◽

Vol 117 (24) ◽

pp. 13699-13707 ◽

Cited By ~ 4

Author(s):

Mercedes Hernando-Pérez ◽

Natalia Martín-González ◽

Marta Pérez-Illana ◽

Maarit Suomalainen ◽

Gabriela N. Condezo ◽

...

Keyword(s):

Core Protein ◽

Human Adenovirus ◽

Adenovirus Type ◽

Binding Pocket ◽

Dynamic Competition ◽

Amino Terminal ◽

Endosome Escape ◽

Virion Structure ◽

High Resolution Structure ◽

Protein Vi

Adenovirus minor coat protein VI contains a membrane-disrupting peptide that 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 noninfectious 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 wild-type (Ad5-wt) particles. Cryoelectron microscopy 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.

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