Studies of the role of cytomegalovirus infection in inflammation and cancer

Human cytomegalovirus (HCMV) is a widespread disease-causing agent belonging to the herpesvirus family. After a primary infection HCMV establishes latency within its host, from which the virus may reactivate throughout life. When healthy individuals become infected by HCMV, they rarely show any symptoms, but in some cases individuals may experience symptoms such as headache, fever, a sore throat and muscle pain. In contrast, individuals with a suppressed immune system, due to medical treatment or disease, may experience severe disease or even death. HCMV-infection of fetuses, acquired during the development in the uterus, is the world leading infectious cause of birth defects. This type of infection might cause damage to visual and hearing senses as well as damages to the central nervous system with manifestations such as mental disorder and hearing loss. Furthermore, HCMV has been suggested to play a role in certain types of cancer. HCMV thrives and reactivates in parts of the body where there is an ongoing inflammation. The site of inflammation offers an environment rich in molecules, which attract latently infected blood cells into inflammatory tissues and reactivates latent HCMV. Because of that, we were interested to study the role of HCMV-infection in connection to inflammation and cancer.

I focused on understanding molecular mechanisms of HCMVpathogenesis and found that: i) HCMV decreases the expression of PDGFR s, which may play an important biological role in congenital HCMV-infection and embryonic development. ii) HCMV induces 5- LO mRNA and protein expression in vascular SMC s, enabling these cells to synthesize LTB4, which offers a molecular mechanism to HCMV-mediated pathogenesis in inflammatory diseases. iii) HCMV alters the balance between MMP-9 and TIMP-1 in macrophages, which may affect atherosclerotic plaque development and stability. iiii) HCMV induces telomerase activity in human fibroblasts and glioma cell lines. This phenomenon is mediated by the presence of IEA at the hTERT proximal promoter, the recruitment of Sp1, decreased HDAC-1 and -2 promoter binding and H3 acetylation.

Our findings provide a novel mechanism that may explain how HCMV induces oncogenesis, a mechanism that may be critical in the understanding of the relationship between HCMV and cancer.

List of scientific papers

I. Gredmark S, Strååt K, Homman-Loudiyi M, Kannisto K, Söderberg-Nauclér C. (2007). "Human cytomegalovirus downregulates expression of receptors for platelet-derived growth factor by smooth muscle cells." J Virol 81(10): 5112-20
https://pubmed.ncbi.nlm.nih.gov/17344284

II. Qiu H, Strååt K, Rahbar A, Wan M, Söderberg-Nauclér C, Haeggström JZ. (2008). "Human CMV infection induces 5-lipoxygenase expression and leukotriene B4 production in vascular smooth muscle cells." J Exp Med 205(1): 19-24
https://pubmed.ncbi.nlm.nih.gov/18180307

III. Strååt K, de Klark R, Gredmark-Russ S, Eriksson P, Söderberg-Nauclér C. (2009). "Infection with human cytomegalovirus alters the MMP-9/TIMP-1 balance in human macrophages." J Virol 83(2): 830-5
https://pubmed.ncbi.nlm.nih.gov/18945772

IV. Strååt K, Liu C, Rahbar A, Zhu Q, Liu L, Wolmer-Solberg N, Lou F, Liu Z, Shen J, Jia J, Kyo S, Björkholm M, Sjöberg J, Söderberg-Nauclér C and Xu D. (2009). "Activation of telomerase by human cytomegalovirus." J Natl Cancer Inst 101(7): 488-97
https://pubmed.ncbi.nlm.nih.gov/19318640