Research

HCMV

Human cytomegalovirus (HCMV) is a herpesvirus that infects a majority of the world’s population, although acute disease is manifested only in a relatively small percentage of infected individuals. Primary infection or reactivation of latent HCMV can lead to life-threatening conditions in immunocompromised individuals, e.g., AIDS patients and organ transplant recipients. HCMV is also the most common congenital virus infection in the United States (1 in 150 children) and can lead to developmental abnormalities or even fetal death. According to recent data from the Centers for Disease Control and Prevention, congenital HCMV infection is responsible for more cases of long-term developmental disorders than Down syndrome, Fetal Alcohol Syndrome, Spina Bifida, or pediatric HIV/AIDS. Moreover, HCMV is the most frequent infectious cause of allograft rejection in solid organ transplant recipients and is also implicated in several cardiovascular conditions such as atherosclerosis and hypertension. At present, a vaccine is not available for the prevention of HCMV infection, and the drugs available for prophylactic therapy in transplant recipients suffer from safety, efficacy and resistance concerns.

Role of tegument proteins in maintaining HCMV capsid integrity

Herpesvirus tegument proteins play important roles in maintaining the structural stability of immature capsids as well as directing the acquisition of virus envelope. The tegument protein pp150 is located on the HCMV nucleocapsid surface and binds to the nuclocapsid directly to provide stability. Another tegument protein pUL96 influences the stability of capsids by a pp150-supported mechanism. We have reported that an interplay of tegument proteins pp150 and pUL96 determine the stability of HCMV nucleocapsids during virus maturation. Projects to elucidate the structural and functional roles of these essential virus proteins in capsid assembly and stabilization are in progress.

Dynamin in CMV maturation

With help from a collaborator at Yale University: Dr. De Camilli (https://medicine.yale.edu/lab/decamilli/) and the work done by a current graduate student, we have developed powerful tools for studying the role of dynamin in CMV maturation. A major advantage of using this system is its inducible nature, which allows it to deplete dynamin in response to our experimentation. We still have only a very limited understanding of most aspects of herpesvirus maturation. Answering questions about cellular organization during herpesvirus maturation is essential for understanding the mechanistic aspects of virus maturation pathways, and for developing potential therapeutic interventions.

Glycosaminoglycans in CMV and SARS-CoV-2 entry

In an effort to gain a better understanding of CMV entry and maturation, we have recently begun to explore how virus particle interact with glycosaminoglycans on cell and endosomal surfaces. We are currently collaborating with Sharp Lab at UM (http://massspec.olemiss.edu) and are looking to expand this work by collaborating with other labs who have the facilities and prior experience to investigate this project further.

Effect of space radiation on CMV lytic replication and reactivation from latency

In collaboration with scientists at NASA's Johnson Space Center, Houston, TX and at The University of Arizona Health Sciences, Tucson, we are investigating the effect of space radiation on HCMV genome as well as on host factors responsible for virus reactivation from latency.