Human cytomegalovirus tegument protein ppUL35 is important for viral replication and particle formation

Karina Schierling1, Christopher Buser, Thomas Mertens

  • 1Abteilung Virologie, Universitätsklinikum Ulm, Albert Einstein Allee 11, D-89081 Ulm, Germany. michael.winkler@medizin.uni-ulm.de

Journal of Virology
|February 15, 2005
PubMed

Insights

Human cytomegalovirus (HCMV) tegument protein ppUL35 is essential for efficient viral replication. Deleting UL35 impairs immediate-early gene expression and virus assembly, highlighting ppUL35's critical role.

Area of Science:

  • Virology
  • Molecular Biology

Background:

  • Human cytomegalovirus (HCMV) tegument proteins ppUL35 and ppUL82 (pp71) interact to activate major immediate-early transcription.
  • The role of ppUL82 in HCMV growth is understood to be multiplicity of infection (MOI)-dependent, but ppUL35's significance remains unclear.

Purpose of the Study:

  • To investigate the biological significance and function of the HCMV tegument protein ppUL35.

Main Methods:

  • Generation of an HCMV mutant virus with a deletion in the UL35 gene.
  • Analysis of viral replication, immediate-early gene expression, and virus assembly at different MOIs.
  • Characterization of viral particle ultrastructure.

Main Results:

  • HCMV UL35 deletion resulted in a 1,000-fold reduction in progeny virus yield at MOI 0.1, and was essential at MOI 0.01.
  • Mutant virus exhibited reduced immediate-early gene expression and delayed lytic gene expression when standardized by viral DNA.
  • Defects in virus assembly were observed, with fewer enveloped particles and absent dense bodies in infected cells.

Conclusions:

  • ppUL35 plays a crucial role in HCMV immediate-early gene expression.
  • ppUL35 is important for efficient HCMV virus assembly.
  • The tegument protein ppUL35 is essential for optimal HCMV replication and infectivity.

Related Concept Videos

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...
Leaky Scanning02:28

Leaky Scanning

During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA.  Marilyn Kozak discovered that the sequence RCCAUGG (where R stands for...
Coat Assembly and GTPases01:33

Coat Assembly and GTPases

Vesicles incorporate different coat protein subunits in different cell locations, which changes the properties of the coat, such as the shape and geometry of the transport vesicles. Thus, vesicle coat proteins also play a significant role in cargo selection.
Coat assembly depends on the local availability of phosphatidylinositol phosphates or PIPs and GTP-binding proteins. Adaptor proteins, which link the coat proteins to the membrane, bind to these PIPs and play a crucial role in controlling...
Inhibitors Of Virion Release01:25

Inhibitors Of Virion Release

Viral replication and dissemination rely on efficient mechanisms for host cell entry, genome replication, assembly, and release. Influenza viruses, such as types A and B, are negative-sense single-stranded RNA viruses with a segmented genome, that depend on two critical surface glycoproteins to carry out these processes: hemagglutinin (HA) and neuraminidase (NA). HA initiates infection by binding to sialic acid residues on the surface of host epithelial cells, facilitating receptor-mediated...
Viral Structure00:56

Viral Structure

Viruses are extraordinarily diverse in shape and size, but they all have several structural features in common. All viruses have a core that contains a DNA- or RNA-based genome. The core is surrounded by a protective coat of proteins called the capsid. The capsid is composed of subunits called capsomeres. The capsid and genome-containing core are together known as the nucleocapsid.