Structural changes in human cytomegalovirus cytoplasmic assembly sites in the absence of UL97 kinase activity

Maysa Azzeh1, Alik Honigman, Albert Taraboulos

  • 1Department of Clinical Microbiology and Infectious Diseases, Hadassah University Hospital, Jerusalem, Israel 91120.

Virology
|July 29, 2006
PubMed

Insights

Human cytomegalovirus (HCMV) UL97 kinase is crucial for viral assembly. Its absence alters viral protein distribution and Golgi remodeling, impacting cytoplasmic assembly sites.

Area of Science:

  • Virology
  • Molecular Biology
  • Cell Biology

Background:

  • Human cytomegalovirus (HCMV) UL97 kinase plays a known role in viral DNA replication, capsid maturation, and nuclear egress.
  • The precise function of UL97 kinase in the cytoplasmic assembly stages of HCMV remains largely uncharacterized.

Purpose of the Study:

  • To investigate the role of HCMV UL97 kinase activity in the cytoplasmic assembly of viral particles.
  • To determine how the absence of UL97 kinase affects the subcellular localization of viral structural proteins and cellular organelles.

Main Methods:

  • Utilized a human cytomegalovirus (HCMV) UL97 kinase deletion mutant (DeltaUL97) and a specific UL97 kinase inhibitor (NGIC-I).
  • Analyzed the subcellular distribution of viral structural proteins using microscopy.
  • Assessed the reorganization of Golgi-related structures (WGA-positive) and nuclear architecture during infection.

Main Results:

  • Absence of UL97 kinase activity led to diffuse perinuclear distribution of viral assembly sites, unlike the compact nuclear-associated structures seen in wild-type infections.
  • Large vacuoles were observed within the modified assembly sites in DeltaUL97 infections.
  • Both wild-type and DeltaUL97 HCMV infections induced significant reorganization of Golgi-related structures, but this remodeling was notably altered in the absence of UL97 kinase activity.

Conclusions:

  • HCMV UL97 kinase activity is implicated in organizing viral cytoplasmic assembly sites.
  • UL97 kinase influences the subcellular localization of viral components and contributes to the remodeling of host cell organelles during viral assembly.

Related Concept Videos

Protein Complex Assembly02:41

Protein Complex Assembly

Proteins can form homomeric complexes with another unit of the same protein or heteromeric complexes with different types.  Most protein complexes self-assemble spontaneously via ordered pathways, while some proteins need assembly factors that guide their proper assembly. Despite the crowded intracellular environment, proteins usually interact with their correct partners and form functional complexes.
Many viruses self-assemble into a fully functional unit using the infected host cell to...
Intralumenal Vesicles and Multivesicular Bodies01:38

Intralumenal Vesicles and Multivesicular Bodies

Intraluminal vesicles (ILVs) are small vesicles 50-80 nm in diameter formed during the maturation of early endosomes. A specialized endosome containing numerous ILVs is called a multivesicular body (MVB). ILVs contain internalized molecules such as antigens, nucleic acids, proteins, and metabolites. Some of these molecules are released from the MVBs inside exosomes and are transported to other cells. Other MVBs contain molecules that are retained in the ILVs and are later degraded within the...
Inhibitors of Virion Maturation and Assembly01:19

Inhibitors of Virion Maturation and Assembly

As part of their replication cycle, certain viruses synthesize long precursor proteins called polyproteins within infected host cells. In human immunodeficiency virus (HIV), two major polyproteins are produced: Gag and Gag-Pol. The Gag polyprotein supplies the structural components of the virus, while Gag-Pol includes essential viral enzymes such as reverse transcriptase, integrase, and protease. After synthesis, these polyproteins move to the host cell membrane, where they assemble into an...
Cytomegalovirus Disease01:27

Cytomegalovirus Disease

Cytomegalovirus (CMV) disease is caused by human cytomegalovirus, a double-stranded DNA virus of the Herpesviridae family. While primary CMV infection is often asymptomatic in immunocompetent individuals, the virus can cause severe disease in neonates and immunocompromised patients. CMV is the most common cause of congenital viral infection in the United States, and a major pathogen in solid organ and hematopoietic stem cell transplant recipients.CMV is transmitted via bodily fluids, sexual...
Anaphase Promoting Complex00:50

Anaphase Promoting Complex

The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
Vesicular Tubular Clusters01:45

Vesicular Tubular Clusters

After budding out from the ER membrane, some COPII vesicles lose their coat and fuse with one another to form larger vesicles and interconnected tubules called vesicular tubular clusters or VTCs. These clusters constitute a compartment at the ER-Golgi interface known as ERGIC (Endoplasmic Reticulum Golgi Intermediate Compartment). The ERGIC is a mobile membrane-bound cargo transport system that sorts proteins secreted from ER and delivers them to the Golgi.
With the help of motor proteins such...