A novel adenovirus 19K/IX protein promotes infection by preventing proteasomal degradation of tyrosine-ubiquitinated pIX

ABSTRACT: Human adenoviruses (HAdVs) are double-stranded DNA viruses that cause a wide range of diseases, including respiratory, ocular, and gastrointestinal infections. HAdVs rely extensively on alternative splicing and polyadenylation to expand their coding capacity and regulate gene expression during infection. Using replication-competent HAdV-C5 viruses engineered with epitope tags, we investigated the function of a newly identified alternatively spliced viral transcript, 19K/IX. We show that the 19K/IX protein stabilizes the minor capsid protein pIX by preventing its proteasomal degradation, thereby increasing viral progeny production. Mechanistically, we demonstrate that pIX degradation is mediated by a non-canonical ubiquitination of conserved tyrosine residues, which also partially mediate pIX interaction with the PSMC3 subunit of the 26S proteasome. Collectively, these findings identify 19K/IX as a regulator of pIX stability and uncover a non-canonical tyrosine ubiquitination mechanism through which HAdVs modulate proteasome targeting to promote infection.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Pneumocyte, Permanent Cell Line Cell, Cell Culture

DISEASE(S): Viral Infectious Disease

SUBMITTER: Mårten Larsson  

LAB HEAD: Tanel Punga

PROVIDER: PXD076227 | Pride | 2026-10-07

REPOSITORIES: Pride