EB3 protein: a promising therapeutic target against HCMV infection
A new study now deepens our understanding of how an extremely common human virus establishes its infection and provides novel targets for anti-viral therapies.
Human cytomegalovirus (HCMV), also referred to as human herpesvirus type 5 (HHV-5), is a member of the Herpesviridae family of viruses which are large DNA viruses. Most adults are infected with HCMV. Once infected, people will harbor lifelong latent reservoirs of HCMV that periodically reactivate. In most cases, HCMV infection is innocuous and causes no symptoms. However, for pregnant women and immunocompromised individuals, HCMV infection can cause severe health consequences. In fact, HCMV is a big cause of perinatal mortality and congenital birth defects such as deafness and learning disabilities. Unfortunately, no cure or vaccine is available to prevent HCMV infection. What’s worse, the awareness of this potentially life-threatening virus is not enough.
One characteristic feature of HCMV infection is the marked reorganization of cellular organelles to form a cytoplasmic viral assembly compartment. After CMV infects a human cell, it creates a structure where proteins are assembled into infectious viral particles. This structure is the so-called assembly compartment. The assembly compartment is required for efficient production of infectious HCMV virions. The newly formed viral particles can escape the cell to invade new ones, spreading infection. But our knowledge of how assembly compartment forms and functions during HCMV infection is far from complete. This hinders the development of preventive and therapeutic strategies against HCMV. One goal of research on HCMV is to understand the biology of the structure assembly compartment.
In this work, the researchers discovered that the assembly compartment is highly dynamic and acts as a microtubule-organizing center that allows the virus to manipulate the cell in a way that facilitates the maintenance of assembly compartment structure and optimal virus replication. In particular, EB3
, a microtubule-associated protein that in humans is encoded by the MAPRE3 gene
, is involved in this process. Furthermore, the researchers developed a peptide that targets EB3 and demonstrated that the peptide indeed suppressed HCMV replication, highlighting the specific role of EB3 in HCMV infection. These results, collectively, not only shed light on how the assembly compartment functions during HCMV infection but also suggest EB3 as a druggable target to suppress HCMV replication.
The researchers have summarized their findings in a paper titled "The HCMV Assembly Compartment Is a Dynamic Golgi-Derived MTOC that Controls Nuclear Rotation and Virus Spread," appearing online April 9, 2018 in the journal Developmental Cell.
Targeting host proteins rather than viral proteins avoids the emergence of drug-resistant viral strains, according to senior author of the study, Dr. Derek Walsh from Northwestern University. Research in Dr. Derek’s laboratory is aimed to understand DNA virus biology, particularly the role of the host translation system during infection by poxviruses as well as microtubule regulation and function during herpes simplex virus infection.
In addition to Northwestern University, the study also involves researchers from the University of Illinois and Baruch S. Blumberg Research Institute.