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National Institute of General Medical Sciences (NIGMS) and National Cancer Institute (NCI) of the National Institutes of Health (NIH)
 

Structure of the human adenovirus capsid

Vijay Reddy group (The Scripps Research Institute) and collaborators

 

The groups of Vijay Reddy and Glen Nemerow at the Scripps Research Institute determined the 3.5-Å structure of the human adenovirus capsid (HAdV). Human adenoviruses (HAdV) are nonenveloped double-stranded DNA viruses associated with acute infections. Some strains are linked to potentially fatal respiratory infections, and severe disseminated diseases also occur in patients receiving bone marrow-derived stem cells. In addition to their disease associations, replication-defective or conditionally replicating HAdVs continue to be evaluated in ~25% of approved phase I to III clinical trials for vaccine and therapeutic gene transfer. With a molecular weight of 150-MDa and nearly one million amino acids, the HAdV capsid holds the world's record as the largest crystal structure determined to near-atomic resolution. The adenovirus capsid contains a number of cement proteins (IIIa, VI, VIII, IX) that mediate interactions between the major capsid proteins (hexon and penton base). The structure revealed direct interactions between the major capsid proteins and a number of cement proteins. Interactions between the ordered region of key cement protein VIII and the hexon subunits on the capsid interior were clearly elucidated. The overall capsid structure provides insights into the virus-host interactions. For example, the interactions between the penton base and peripentonal hexons are rather tenuous in contrast to the extensive inter-hexon contacts that also are augmented by the cement proteins. This observation favors models of capsid disassembly by release of the penton complex during cell entry. Improved knowledge of HAdV assembly from its individual capsid proteins could lead to the development of novel antiviral strategies to block infection at multiple cell entry steps and also facilitate the development of HAdV vectors with improved tissue targeting.

Figure: Adenovirus capsid [PDB ID 1VSZ].

 

Citation:
Reddy, VS, Natchiar, SK, Stewart, PL, Nemerow, GR. Crystal Structure of Human Adenovirus at 3.5 Å Resolution, Science 329, 1071-1075 (2010). DOI: 10.1126/science.1187292


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