Page 16 - O. Microbiology

[O. Microbiology-16]

The role of palmitoylation of tegument protein pp28 during

human cytomegalovirus infection

Jae Bong Lee¹, Jun-Young Seo¹˙*

¹Severance Biomedical Science Institute, Brain Korea 21 PLUS Project for Medical Science, Yonsei University

College of Medicine, Seoul 03722, Republic of Korea

Human cytomegalovirus (HCMV) tegument protein pp28 is essential for the final envelopment during viral
maturation. This protein undergoes lipidation modifications such as myristoylation and palmitoylation, which affect

the activity and subcellular targeting of proteins. The pp28 protein localizes to the assembly compartment (AC) late

in infection and its localization depends on myristoylation. Myristoylation of pp28 is also necessary for the
production of infectious virions. Meanwhile, plamitoylation of pp28 remains poorly understood. Here, we show that
pp28 is palmitoylated at cysteine residues (aa 6, 10, 11). Inhibition of palmitoylation by site-directed mutagenesis

or palmitoylation inhibitor 2-bromopalmitate treatment disrupts the subcellular localization of pp28 and also
reduces the stability of the protein in transiently transfected cells. The recombinant HCMV producing pp28 mutant

in which three cysteine residues (aa 6, 10, 11) are substituted with alanine residues, exhibits delayed viral growth
kinetics and decreases viral yield, although the recombinant virus is able to produce infectious virions. Our data

indicate that palmityolation at the N-terminal cysteine residues of pp28 plays a critical role in its localization and
stability for efficient viral replication.