Persistent Enterovirus Infection: Little Deletions, Long Infections

Area of Science:

• Virology
• Molecular Biology
• Genomics

Background:

• Enteroviruses can persist in hosts and cell cultures.
• A novel mechanism involves deletions in the 5' terminal genomic region, known as domain I or the cloverleaf.

Purpose of the Study:

• To investigate the mechanism of enterovirus persistence through 5' terminal genomic deletions.
• To characterize the biology of enteroviruses with terminal deletions (TD) using coxsackievirus B3 (CVB3) molecular clones.

Main Methods:

• Utilizing molecular clones of CVB3 with varying 5' terminal deletions (TD).
• Studying the replication of TD enteroviruses in the absence of wildtype genomes.
• Analyzing the conditions under which TD variants emerge and dominate.

Main Results:

• TD enteroviruses replicate independently of wildtype genomes.
• TD variants become dominant in quiescent cell populations.
• Deletions can also be induced by artificial mutation of the cis-acting replication element (CRE-2C).
• TD enteroviruses display significant differences from canonical enteroviral biology.

Conclusions:

• Enterovirus persistence is facilitated by 5' terminal genomic deletions.
• TD genomes have unique replication strategies and host interactions.
• Understanding TD enteroviruses offers insights into viral evolution and pathogenesis.