Related Experiment Videos
Human cytomegalovirus immediate early proteins and cell growth control
Jonathan P Castillo1, Timothy F Kowalik
1Program in Immunology and Virology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA.
Abstract:
It is widely accepted that small DNA tumor viruses, such as adenovirus, simian virus 40 and papillomavirus, push infected cells into S-phase to facilitate the replication of their genome. Until recently, it was believed that the large DNA viruses (i.e. herpesviruses) functioned very differently in this regard by inducing a G(1) arrest in infected cells as part of their replication process. However, studies over the last 6-8 years have uncovered striking parallels (and differences) between the functions of the major immediate early (IE) proteins of at least one herpesvirus, human cytomegalovirus (HCMV) and IE equivalents encoded by small DNA tumor viruses, such as adenovirus. Similarities between the HCMV major IE proteins and adenovirus IE proteins include targeting of members of the RB and p53 families and an ability of these viral factors to induce S-phase in quiescent cells. However, unlike the small DNA tumor virus proteins, individual HCMV IE proteins target different RB family members. HCMV also encodes several other IE gene products as well as virion tegument proteins that act early during infection to prevent an infected cell from replicating its host genome and from undergoing apoptosis. Here, we review the specifics of several HCMV IE proteins, two virion components, and their functions in relation to cell growth control.
Insights
Human cytomegalovirus (HCMV) major immediate early (IE) proteins share similarities with small DNA tumor virus proteins, targeting cell cycle regulators to induce S-phase. However, HCMV proteins also prevent host genome replication and apoptosis.
Area of Science:
- Virology
- Molecular Biology
- Cell Cycle Regulation
Background:
- Small DNA tumor viruses induce S-phase for genome replication.
- Large DNA viruses, like herpesviruses, were thought to induce G(1) arrest.
- Recent studies reveal parallels between herpesvirus and small DNA tumor virus immediate early (IE) proteins.
Purpose of the Study:
- To review the functions of human cytomegalovirus (HCMV) IE proteins and virion components.
- To compare HCMV IE proteins with IE proteins of small DNA tumor viruses.
- To elucidate the role of HCMV proteins in controlling host cell growth.
Main Methods:
- Review of existing literature on HCMV and small DNA tumor virus IE proteins.
- Analysis of protein interactions with host cell cycle regulators (RB and p53 families).
- Examination of viral strategies to manipulate host cell cycle and prevent apoptosis.
Main Results:
- HCMV major IE proteins, like adenovirus IE proteins, target RB and p53 families.
- HCMV IE proteins can induce S-phase in quiescent cells.
- Unlike small DNA tumor viruses, individual HCMV IE proteins target different RB family members.
- HCMV also employs other IE and tegument proteins to inhibit host genome replication and apoptosis.
Conclusions:
- HCMV utilizes sophisticated mechanisms involving IE proteins to control host cell cycle.
- HCMV IE proteins exhibit both conserved and distinct functions compared to small DNA tumor virus IE proteins.
- HCMV actively manipulates host cell processes, including S-phase entry, genome replication, and apoptosis, for its own replication.