Human cytomegalovirus (CMV) is a ubiquitous virus with the ability to establish latency (dormancy) following primary infection, and can be reactivated particularly during episodes of immunosuppression. Once someone has been infected with CMV they have it for life. However, infections in healthy immunocompetent people are usually subclinical and asymptomatic, and the virus does not generally present a health risk to these individuals. However, CMV can cause severe illness for babies infected in utero during pregnancy and immunocompromised individuals such as transplant recipients undergoing immunosuppressive therapy.
Following the successful global introduction of rubella immunisation programs, CMV has become the most common viral cause of congenital malformation in developed countries like Australia. Congenital CMV infections of the fetus occur in approximately 0.3-0.6% of live births and 10-15% of these infections will be symptomatic, where petechiae, jaundice, hepatosplenomegaly, and central nervous system (CNS) involvement are common findings. Although rare, cytomegalic inclusion disease (CID) is a devastating illness that results from overwhelming congenital CMV infection involving multiple organs, which in the most severe cases can lead to intrauterine and perinatal death. Late onset sequelae such as sensorineural hearing loss (SNHL) and mental disability are also associated with fetal CMV infection during pregnancy. CMV infections are transmitted from mother to baby across the placenta. The CMV antiviral agents currently available for CMV cannot be used in pregnant women because of toxicity and other potential side effects.
CMV can also cause severe illness (hepatitis, pneumonitis, chronic gastroenteritis) in immunocompromised transplant recipient, which can lead to organ failure and death in severe cases. CMV exposure prior to transplantation and donor/recipient CMV immunity are important factors influencing the outcome of CMV infection in these patients. Treatment and prophylaxis with antiviral agents such as valganciclovir can reduce the impact of CMV infection and disease in transplant recipients, but emergence of antiviral resistant CMV can occur, and these infections become difficult to manage.
The CMV program is investigating the pathogenesis of CMV infection in at-risk groups. The research aims of the group are to:
1. Understand the pathogenic consequences of CMV placental infection and transmission, including the molecular and cellular changes induced by CMV replication. We particular look at CMV-induced cytokine changes in the placenta and the role these have in placental damage and adverse fetal outcomes.
2. Determine the viral and host factors that contribute to the outcome of CMV infection in transplant recipients.
3. Identify and characterise emerging antiviral resistant CMV strains
4. Investigate novel antiviral targets and potential intervention strategies that in the future may reduce or prevent CMV disease in babies and transplant recipients.
Most Recent Publications
– Hamilton ST, Marschall M, Rawlinson WD (2020). Investigational antiviral therapy models for the prevention and treatment of congenital cytomegalovirus infection during pregnancy. Antimicrobial Agents and Chemotherapy. doi: 10.1128/AAC.01627-20
– Bartlett AW, Hamilton ST, Shand AW, Rawlinson WD (2020). Fetal therapies for cytomegalovirus: what to tell prospective parents. Prenatal Diagnosis. doi: 10.1002/pd.5692
– Naing Z*, Hamilton ST*, van Zuylen WJ, Scott G, Rawlinson WD (2020). Differential expression of PDGF receptor-alpha in human placental trophoblasts leads to different entry pathways by human cytomegalovirus strains. Nature Scientific Reports. 10(1):1082 (*Joint First Authors)
– Häge S, Horsch D, Stilp AC, Kicuntod J, Müller R, Hamilton ST, Egilmezer E, Rawlinson WD, Stamminger T, Sonntag E, Marschall M (2020). A Quantitative Nuclear Egress Assay to Investigate the Nucleocytoplasmic Capsid Release of Human Cytomegalovirus. Journal of Virological Methods. 283:113909
– Singh K, Palasanthiran P,Hamilton ST, Rawlinson WD (2020). Cotton Wool Balls Are an Effective Urine Collection Tool for CMV PCR for Diagnosing Congenital Cytomegalovirus Infection. Pathology. 52(4): 504506
– Wong DD, van Zuylen WJ, Hamilton ST, Steingruber M, Sonntag E, Marschal M, Rawlinson WD (2019). Patient-derived cytomegaloviruses with different ganciclovir sensitivities from UL97 mutation retain their replication efficiency and some kinase activity in vitro. Antimicrobial Agents and Chemotherapy. 63(9): e02425-18
– Shand A, Palasanthiran P, Rawlinson WD (2019) Pre-conception care: an important yet underutilized preventive care strategy. Medical Journal of Australia. 210(9):429
– Lazzaro A, Vo ML, Zelter J, Rawlinson WD, Nassar N, Daly K, Lainchbury A, Shand A (2019). Knowledge of congenital cytomegalovirus (CMV) in pregnant women in Australia is low, and improved with education. Australia and New Zealand Journal of Obstetrics and Gynaecology. doi: 10.1111/ajo.12978
– Wong DD, van Zuylen WJ, Craig ME, Rawlinson WD. (2018). Systematic review of ganciclovir pharmacodynamics during the prevention of cytomegalovirus infection in adult soild organ transplant recipients. Reviews in Medical Virology. 29(2):e2023
– Huynh KT, van Zuylen WJ, Ford CE, Rawlinson WD (2018). Selective modulation of Wnt-binding receptor tyrosine kinase ROR2 expression by human cytomegalovirus regulates trophoblast migration. Journal of General Virology 100(1): 99-104
– Hamilton ST, Hutterer C, Egilmezer E, Steingruber M, Milbradt J, Marschall M, Rawlinson WD (2018). Human cytomegalovirus utilises cellular dual-specificity tyrosine phosphorylation-regulated kinases during placental replication. Placenta. 72-73:10-19
– Hahn F, Hutterer C, Henry C, Hamilton ST, Strojan H, Kraut A, Schulte U, Schutz M, Kohrt S, Wangen C, Pfizer J, Coute Y, Rawlinson WD, Strobl S, Marschall M. (2018). Novel cytomegalovirus-inhibitory compounds of the class pyrrolopyridines show a complex pattern of target binding that suggests an unusua mechanism of antiviral activity. Antiviral Research. 159: 84-94