Title |
Phosphorylation of tegument protein pp28 contributes to trafficking to the assembly compartment in human cytomegalovirus infection |
Author |
Jun-Young Seo1*, Jin Ah Heo1, and William J. Britt2 |
Address |
1Severance Biomedical Science Institute, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Republic of Korea, 2Departments of Microbiology, Pediatrics, and Neurobiology, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA |
Bibliography |
Journal of Microbiology, 58(7),624-631, 2020,
|
DOI |
10.1007/s12275-020-0263-5
|
Key Words |
pp28 tegument protein, phosphoprotein, human
cytomegalovirus, trafficking, assembly compartment, ERGIC |
Abstract |
Human cytomegalovirus (HCMV) UL99 encodes a late tegument
protein pp28 that is essential for envelopment and
production of infectious virus. This protein is localized to
the endoplasmic reticulum-Golgi intermediate compartment
(ERGIC) in transfected cells but it localizes to the cytoplasmic
assembly compartment (AC) in HCMV-infected cells. Trafficking
of pp28 to the AC is required for the assembly of infectious
virus. The N-terminal domain (aa 1-61) of pp28 is
sufficient for trafficking and function of the wild type protein
during viral infection. However, residues required for
authentic pp28 trafficking with the exception of the acidic
cluster in the N-terminal domain of pp28 remain undefined.
Monitoring protein migration on SDS-PAGE, we found that
pp28 is phosphorylated in the virus-infected cells and dephosphorylated
in the viral particles. By generating substitution
mutants of pp28, we showed that three serine residues
(aa 41–43) and a tyrosine residue (aa 34) account for its phosphorylation.
The mutant forms of pp28 were localized to the
plasma membrane as well as the ERGIC in transfected cells.
Likewise, these mutant proteins were localized to the plasma
membrane as well as the AC in virus-infected cells. These results
suggested that phosphorylation of pp28 contributes to
its intracellular trafficking and efficient viral assembly and
incorporation. |