Oral Presentation Australian Society for Microbiology Annual Scientific Meeting 2014

Host-elicited innate immune defense against alphaviral infection: A double-edged sword (#29)

Suan-Sin Foo 1 , Terk-Shin Teng 2 , Weiqiang Chen 1 , Lara J. Herrero 1 , Keh-Chuang Chin 2 3 , Alberto Mantovani 4 5 , Lisa F.P. Ng 2 6 , Suresh Mahalingam 1
  1. Institute for Glycomics, Griffith University, Gold Coast, QLD, Australia
  2. Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Biopolis, Singapore
  3. Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
  4. Humanitas Clinical and Research Center, Department of Inflammation and Immunology, Rozzano, Italy
  5. Department of Biotechnology and Translational Medicine, University of Milan, Milano, Italy
  6. Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
Chikungunya virus (CHIKV) and Ross River virus (RRV) are arthropod-borne viruses associated with large epidemics worldwide, causing widespread distribution of alphaviral-induced arthritis. Rising prevalence of alphavirus infections and critically, the lack of therapeutic treatment warrants urgent attention to elucidate the innate immune responses elicited, which serves as the first line of host defense against alphavirus. Ironically, robust innate immune responses elicited have been associated with both protective and pathogenic outcomes1 . Previously, high expression of viperin was detected in CHIKV-infected patients PBMCs specimens. Further functional and mechanistic studies performed revealed antiviral properties during CHIKV infection2 . Here, we further explored the role of another indispensable acute phase innate immune protein pentraxin 3, which demonstrated an opposing role in alphaviral infection. Contrastingly, PTX3 demonstrated pathogenic characteristics that contributed to alphavirus pathogenesis. In vivo and in vitro studies of PTX3-deficient (PTX3-/-) mice and PTX3-overexpressing HEK293T cells provided direct evidence of enhanced disease and viral replication during acute RRV disease3 . Collectively, these data emphasize the significance of our understanding on the sophisticated innate immune responses elicited during alphaviral infection. Careful manipulation of these innate immune proteins may contribute to future development of therapeutic interventions.
  1. Foo, S. S.* and Chen, W.*, et al. (2011). The genetics of alphaviruses. Future virology, 6(12), 1407. (* Joint 1st author)
  2. Teng, T. S.* and Foo, S. S.*, et al. (2012). Viperin restricts chikungunya virus replication and pathology. Journal of Clinical Investigation, 122(12), 4447-4460. (* Joint 1st author)
  3. Foo, S.S., et al. (2014). Pathogenic role of long pentraxin 3 in enhancing alphaviral disease through N-terminal domain interaction. Manuscript in preparation.