Recombinant adenovirus design — functional role of E1A/E1B deletions In constructing replication-defective recombinant adenovirus vectors for gene delivery, the E1A/E1B region is commonly deleted. What is the principal reason this deletion prevents autonomous viral replication in normal host cells?

Introduction / Context:
Adenoviral vectors are widely used in gene therapy and vaccine development because they can infect dividing and non-dividing cells and yield high transgene expression. To ensure safety and control, these vectors are often rendered replication-defective by deleting specific early genes, notably E1A and E1B.

Given Data / Assumptions:

• E1A and E1B are early genes expressed soon after adenovirus entry.
• Replication-defective vectors lack E1 functions and therefore require complementation in producer cell lines (for example, HEK 293 cells).
• The question asks why deleting E1A/E1B blocks autonomous replication.

Concept / Approach:

E1A acts as a master transcriptional regulator that drives the expression of other early viral genes and pushes host cells into a replication-permissive state by modulating cell-cycle regulators. E1B stabilizes viral mRNAs and helps counteract host defenses, including apoptosis. Together, E1A/E1B establish the molecular environment for efficient viral DNA replication. Removing this region prevents the virus from activating the necessary early transcriptional program.

Step-by-Step Solution:

Verification / Alternative check:

In laboratory production, HEK 293 cells supply E1 functions, enabling growth of E1-deleted adenoviral vectors. Outside such cells, the vectors enter but cannot replicate, confirming the essential role of E1A/E1B.

Why Other Options Are Wrong:

Nonessential genes (option b) can be deleted without blocking replication—this is untrue for E1. Capsid-only roles (option c) and packaging-only roles (option d) mischaracterize E1. Latency-only function (option e) is incorrect; adenoviruses do not have a true latent program like herpesviruses.

Common Pitfalls:

Confusing structural genes with regulatory early genes; assuming any early region is dispensable. E1 is uniquely critical to launch the replication program.

Final Answer:

They encode transcriptional regulators essential for initiating and sustaining viral replication